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Thalassemia in black americans.	What is the age of studied population ?	59 years	40,794	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the outcome of the study ?	The suprapubic catheter was removed surgically and replaced with a functioning catheter; the patient was discharged with urology outpatient follow-up.	40,795	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the studied population ?	A 59-year-old man with a history of schizophrenia, diabetes, hypertension, antibiotic-resistant urinary tract infection, urethral stricture requiring suprapubic catheter, and vesiculo-cutaneous fistula.	40,796	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the number of the studied population ?	1	40,797	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the study design of this article ?	Case report	40,798	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the condition of the studied population ?	The patient had a nonfunctioning suprapubic catheter encased by bladder calculi, leading to urinary retention and catheter obstruction.	40,799	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the studied or evaluated intervention ?	Open cystolitholapaxy (surgical removal of bladder stones) and removal and replacement of the suprapubic catheter.	40,800	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the studied indication ?	Suprapubic catheter dysfunction leading to acute urinary retention.	40,801	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What are the comparators ?	Urethral catheterization (as a comparative discussion point in the article).	40,802	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What did improve quality of live ?	Removal of the obstructed catheter and surgical intervention to eliminate the bladder stone.	40,803	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Any adverse events or complications reported ?	No adverse events or complications were reported post-procedure; the patient tolerated the procedure well.	40,804	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What are the primary outcomes ?	Removal of the encrusted suprapubic catheter and resolution of urinary retention.	40,805	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What are the secondary outcomes ?	Not explicitly mentioned in the context.	40,806	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Was the magnitude of the treatment effect observed clinically significant ?	Yes; the patient was successfully treated with surgical intervention and discharged, indicating a clinically significant improvement.	40,807	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Has a statistical analysis of the data been provided and is it appropriate ?	No statistical analysis was provided, as the study is a single case report.	40,808	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	What is the target device ?	Suprapubic catheter	40,809	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Was the device used for the same intended use (e.g., methods of deployment, application, etc.) ?	Yes; the suprapubic catheter was used for its intended purpose of managing chronic urinary retention.	40,810	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Was the data generated from a patient group that is representative of the intended treatment population e.g., age, sex, etc.) and clinical condition (i.e., disease, including state and severity) ?	No; the data is from a single patient case and may not be representative of the broader intended treatment population.	40,811	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Was the data Bench Simulation ?	No	40,812	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Do the reports or collations of data contain sufficient information to be able to undertake a rational and objective assessment ?	Yes; the report provides detailed clinical information allowing for a rational and objective assessment.	40,813	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Do the outcome measures reported reflect the intended performance of the device ?	Yes; the outcomes related to catheter functionality and resolution of urinary retention reflect the intended performance of the suprapubic catheter.	40,814	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the Population as nominals .i.e give short answers	59-year-old man	40,815	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the Indication as nominals .i.e give short answers	Suprapubic catheter dysfunction; acute urinary retention	40,816	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the Comparators as nominals .i.e give short answers	Urethral catheterization	40,817	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the Outcomes as nominals .i.e give short answers	Suprapubic catheter removal; surgical removal of bladder stone; patient discharged with outpatient follow-up	40,818	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the Study Type as nominals .i.e give short answers	Case report	40,819	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the target devices as nominals	Suprapubic catheter	40,820	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Thalassemia in black americans.	Extract the follow-up duration from the study, distinguishing different subgroups if necessary. If different follow-up periods are reported, list them separately.	The patient was discharged with urology outpatient follow-up. No specific follow-up duration was provided.	40,821	182,191	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the age of studied population ?	"18–85 years"	40,850	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the outcome of the study ?	"Occurrence of foot ulceration; adherence to daily two-time temperature measurement; alert frequency; detection of slow temperature drops; safety (AEs and SAEs); precursors of the primary endpoint; quality of life"	40,851	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the studied population ?	"300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (risk class 2 or 3)"	40,852	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the number of the studied population ?	"300 patients"	40,853	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the study design of this article ?	"Open-label randomized controlled trial"	40,854	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the condition of the studied population ?	"High-risk patients with diabetes and severe diabetic peripheral neuropathy (risk class 2 or 3)"	40,855	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Study protocol for a randomized controlled trial to test for preventive effects of diabetic foot ulceration by telemedicine that includes sensor-equipped insoles combined with photo documentation.	What is the studied or evaluated intervention ?	"Twice-daily recording of foot temperatures with the sensor-equipped insole (Medixfeet Insole®) and the Smart Prevent Diabetic Feet Application (SPDFA) including a telemedicine structure with a remote server and smartphone app for feedback and alarming"	40,856	185,560	Background According to the definition of the World Health Organization (WHO), diabetic foot syndrome (DFS) encompasses all foot complications, constituting an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection” []. It increases the risk of limb amputation, and even mortality, if left untreated []. In Germany, about 40,000 legs, feet, or toes are amputated, with 70% of major amputations and 85% of minor amputations due to DFS. In addition, foot lesions in diabetic patients impose an enormous social and economic burden across the world. In the US, Rogers et al. reported that $18 billion were spent on the care of diabetic foot ulcers (DFUs) and $11.7 billion sum up as consequences of lower extremity amputations []. Among the reasons for DFS, diabetic foot neuropathy is the major contributing factor for foot complications (50% as a single cause, 30–50% as a cause in combination with angiopathy []), because it affects the ability of the foot to feel and sense [–]. This is why patients with diabetic neuropathy are not able to realize injuries to their feet. Most of the complications develop due to infection and ulceration in the foot [, ]. The early signs of DFS include fissures, blisters, abundant callus formation, redness, and increased temperature []. A physician may diagnose the exact cause by analyzing these physical features []. It is possible to delay or even avoid the development of DFUs with adequate treatment at early stages. Usually, clinicians assess the general condition through analyzing ankle brachial pressure indices, plantar pressure profiles, and testing for foot neuropathy []. Additionally, advanced technologies like corneal confocal microscopy, magnetic resonance tomography, and Doppler ultrasonography provide tools to diagnose the prevalence of peripheral neuropathy and angiopathy, foot ulcers, and its risks []. However, these methods are considered intrusive and are costly; patient compliance is lacking, especially with frequent doctor’s visits []. On the other hand, patient self-assessment has limitations such as lack of knowledge about this condition, difficulties using specialized equipment, and impaired physical mobility. More effective and advanced approaches need to be investigated to provide flexible and comprehensive foot care for patients at risk for the DFS. Elevated plantar temperatures have been reported to be an early sign of incipient DFUs. In the studies of Lavery et al. and Armstrong et al., home temperature monitoring and reduced activities have been verified to be effective to reduce the incidence of DFUs in high-risk patients [, ]. In the study of Lazo-Porras et al., the effectiveness of foot thermometry (TempStat™ for thermal image capture) to prevent DFUs was investigated, together with mHealth reminders (SMS and voice messaging), in an evaluator-blinded randomized 12-month trial. The authors highlighted the importance to evaluate adherence to daily home-based measurements []. Furthermore, a left-to-right foot temperature difference of > 2.2 °C as a proposed threshold for an impending ulceration has been investigated comprehensively by Wijlens et al. in 20 patients with diabetes and peripheral neuropathy. Their conclusion was that the > 2.2 °C threshold is only acceptable if it is confirmed after 24 h in a repeated measure and if, in addition, the temperature difference is individually corrected depending on baseline measurements []. In addition to neuropathic ulcers [, ], one has to consider osteomyelitis [, ] and the disease termed Charcot foot [] as differential diagnoses in the case of elevated plantar temperatures. On the other hand, decreased foot temperatures may point to a vascular insufficiency in the foot []. Therefore, foot temperature monitoring with thermometers, thermal imaging techniques, wearable temperature techniques (socks, insoles, and shoes) has been widely tested to date. For example, Netten et al. explored the temperature discrimination thresholds between “no,” “local,” or “diffuse” DFUs with a high-resolution infrared thermal imaging technique []. Fraiwan et al. implemented a mobile thermal imaging system with an automated method to identify possible ulcers in diabetic patients []. These pioneering works may open a window for patients to check for their foot condition in a feasible and comfortable fashion in the future. Moreover, in the study by Fryberg et al., a novel smart mat technology was evaluated for predicting impending DFUs in a 34-week cohort study that enrolled 132 patients with diabetes. Their results support the notion that the remote temperature-monitoring system could be a feasible and efficient strategy to early identify DFUs, but the asymmetry thresholds have a significant influence on the sensitivity and specificity. Comparing the 2.22 °C and 3.20 °C thresholds, sensitivity decreased from 97% to 70%, but the specificity increased from 43% to 68% []. Therefore, effective and convenient means of temperature measurements such as home-based wearable technologies, accurate and reasonable early warning mechanisms with disparate asymmetry thresholds, followed by timely and appropriate interventions are the main research focus in this field. From our perspective, home-based monitoring of plantar foot temperatures may be regarded as an effective method in the early detection and possible prevention of DFUs. In this study, by utilizing a novel sensor-equipped insole, we aim to establish a telemedicine structure with a remote server and the corresponding smartphone app to timely monitor changes of plantar foot temperatures in diabetes patients. The evidence obtained will include a set-up with predefined standardized temperature recordings and a telemedicine aspect allowing for feedback and alarming as well as picture recordings. The outcome of our study will ultimately allow us to determine if and to which extent such an effort may reduce the number of diabetic foot ulcerations and other medical foot conditions in such a cohort. Methods/Design Objectives The present study aims to investigate the hypothesis that a twice-daily recording of foot temperatures with the aid of the sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH) can reduce the risk of ulcer formation. Primary specific aim The primary objective of the present study was to compare the incidence of DFUs during the study period between patients who only receive education about regular foot care and those patients who additionally proceed with daily measurements of foot temperatures with the sensor-equipped insole, together with an app-based warning system and self-imaging of feet for incipient ulcer development. Secondary specific aims The secondary objectives of the present study were to: collect safety-relevant information concerning the equipment (insole) frequency of adverse events (AEs)frequency of serious adverse events (SAEs)quantify precursors of the primary endpoint redness in the foot areainfections in the foot areawounds in the foot areaevaluate the changes of quality of life independent of primary and secondary endpointsassess the adherence to daily two-time temperature measurements based on data acquisition by the apprecord the alarm frequency in the intervention group based on data collected by the appdetect “slow” temperature drops as an indicator of circulatory disordersassess the adherence to photo documentation Study design This open-label trial will randomize 300 high-risk patients with diabetes and advanced polyneuropathy, that lack severe peripheral angiopathy, into two groups with a 1:1 ratio. At the screening visit, all potential study participants will first be informed about the aim and purpose of the study. They will be interviewed for past medical foot problems with documentation thereof and will thereafter be examined for polyneuropathy and blood circulation disorders (see below). Regarding the study-specific inclusion and exclusion criteria (compare Fig. ), the study physician informs the patient about their possible suitability for participation and the modalities of the study. If patients are eligible for the protocol, they will be enrolled only after giving informed consent (see Additional file ). In a next step, patients will be randomized into control or intervention group in a ratio of 1:1. Two weeks later, at visit 0, they will be trained by a qualified study physician about regular foot care measures to prevent foot ulcers (standardized patient education) (see Additional file ). The non-intervention group will not undergo any further immediate intervention; however, research participants in this group will be seen at regular follow-up visits at six-month intervals (Fig. ). In the intervention group, every patient receives a pair of slippers with inserted sensor-equipped insoles as well as a smartphone with a Smart Prevent Diabetic Feet Application (SPDFA) (Fig. , see Additional file ). They will perform measurements of their foot temperatures twice a day at home, with time intervals > 4 h during the entire study course, which comprises 24 months. In case of temperature differences > 1.5 °C between left and right corresponding sensor sites, and lasting > 32 h, the study participant will be instructed to reduce daily activities and relax his feet for five days. Additionally, the participant will receive a notification by the app to take pictures with his smartphone from the dorsal and (possibly with help of care providers) plantar feet that are transferred to the study center. In the app, essential guidance and foot masks help the patient to capture standardized foot images (Fig. ). Depending on the findings of the photo documentation, additional visits to the study center to perform clinical examinations will be arranged for the patient during this intervention period. In addition, patients in both groups are required to consult a physician when early signs of foot ulceration are noted by self-inspection of the feet (e.g. redness, pain, sores). Follow-up visits are carried out after enrollment in the study at months 6, 12, 18, and 24 by a registered nurse and a physician trained to diagnose and treat DFS. Visits 1 and 3 (after 6 and 18 months, respectively) encompass the evaluation of patient’s foot status, control of unexpected events, summary of endpoints, and assessment of the collected sensor data. Visits 2 and 4 (after 12 and 24 months, respectively) additionally include the assessment of outcome measures, patient’s wellbeing evaluation by WHO-5-questionaire, as well as taking pictures with normal illumination and infrared light from the patient’s feet (Fig. ). The primary endpoint of the study is DFU formation (more precisely, the time until ulcers form) and the total number of ulcerations in each group. Secondary endpoints will include evaluation of AEs and SAEs, precursors of the primary endpoint as listed above, assessment of quality of life using an interactive patient’s diary (Fig. ), patient compliance, information about temperature alarms—including “slow” temperature drops, and acquisition of photo documentation. If a foot ulcer occurs in a patient, it will be treated according to the usual measures of standard clinical care. Possible discontinuation of the study occurs according to the defined termination criteria (Fig. ). The SPDFA receives the measured data of the sensor-equipped insole via low-energy Bluetooth® connectivity. It then performs an initial analysis of temperature differences and visualizes these. Thereafter, the temperature recordings are transferred from the SPDFA to a study server. This server is located in the premises of the computer center of the Medical Faculty of the Otto-von-Guericke University Magdeburg. The data may be exported from the study server in a suitable format (SAS / SPSS) for statistical analysis at the Institute of Biometry and Medical Informatics. The final report will be compiled no later than one year after the end of the study. Participant recruitment and selection criteria Recruitment is carried out by practicing diabetologists and podiatrists in the Polyclinic of the University Hospital Magdeburg. The study will enroll 300 patients aged 18–85 years with type 1 or type 2 diabetes mellitus and exhibiting severe diabetic peripheral neuropathy (vibration sensation ≤ 4/8) with or without a history of ulceration. They will be eligible only when they are classified as high-risk patients, i.e. risk class 2 or 3 as defined by the diabetic foot risk classification system (as specified by the IWGDF) [, ]. It is based on a short questionnaire about previous history of ulceration and/or partial foot amputation, foot evaluation to detect bunion, rigid deformities (such as hammer digit or claw toe), and prominent metatarsal heads, as well as neuropathy testing using the vibration perception threshold and the Semmes-Weinstein monofilament []. The participants of the study have to be able to use a smartphone and its applications. The study excludes patients with active ulcer, arthropathy, tumor disease, as well as those with foot infection, macroangiopathy of the lower extremities (ABI < 0.5), heart failure classes III/IV according to NYHA, physical deformities (amputations, foot, leg, spinal deformities affecting the gait), visual impairment that limits normal use of smartphones, myocardial infarction within 12 weeks before study protocol inclusion, or pregnancy. The principal investigator has the right to preclude participation due to any reason in his personal opinion and in accordance with the inclusion and exclusion criteria as summarized (Fig. ). Baseline data collection At the screening visit, the study physicians record the past medical history by means of a foot documentation sheet recommended by the Foot Working Group of the German Diabetes Society. It includes the following items: Previous foot lesions, deformities, and surgeriesDetails about the previous shoe supplyPresence of blood supply disorders (ischemia and PAD)Burning, numbness, weakness, cramps or pain in the legs and feet In addition to the interview, a series of tests are carried out to determine the degree of polyneuropathy and blood supply disorders: Monofilament test to check the sensation of touch and pressureTip-Therm Test to check the temperature sensationTuning fork test for measuring depth sensitivity and vibration sensationTesting the sensation of pain with a disposable needleDoppler ultrasound test for the measurement of circulatory disordersMuscle self-reflex statusBlood pressure measurement (for ABI) If patients are eligible for the protocol, the study physician obtains informed consent at screening visit through a written consent form with the signature of the potential trial participant. Randomization In the University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, randomization is performed using the software RITA (from Statsol, Lübeck). Three hundred patients will be assigned to two groups with a 1:1 ratio based on a stratification according to the prevalent risk group (2 or 3), gender, age (< 60 years vs ≥ 60 years), and the degree of neuropathy (restriction of vibration sensation, using the minimization algorithm of Pocock and Simon []). Randomization to the study protocol will be based on the intention-to-treat principle. The randomization is not concealed to the physicians and to the study population at any time after informed written consent of the patients. Intervention The sensor-equipped insole (Medixfeet Insole®, Thorsis Technologies GmbH, Magdeburg, Saxony-Anhalt, Germany) features six temperature sensors that measure the foot temperatures at different locations. These are the plantar hallux (D1), the first, third, and fifth metatarsal heads (MTK1, MTK3, and MTK5), the mid-foot (lateral), and the heel (calcaneus). From our previous experience considering both energy and performance aspects, the duration of each single measurement is set at 3 min using a measuring frequency of 2 Hz. The measured temperature data will be transferred via Bluetooth® to a smartphone. For this study, an alarm algorithm with five alarm levels was developed that can be visualized on both the study server (for the physician) and the SPDFA (for the patient). In the algorithm, a “warning signal” will be prompted if temperature differences are > 1.5 °C between left and right corresponding sensor sites (Fig. ). The following levels have been implemented: level 0 = no “warning signal”; alarm level 1 = first “warning signal”; alarm level 2 = second “warning signal” after at least 4 h; alarm level 3 = third “warning signal” after at least 20 h; alarm level 4 = fourth “warning signal” after at least 32 h. Only the study physician can reset alarm level 4 to level 0 after evaluation. Other eventful alarm levels (levels 1–3) will automatically reset to level 0 if the initially detected “warning signal” is no longer reinforced. The above-mentioned alarm level is not one sensor-specific alarm but reflects the highest alarm level of all six pairs of sensor sites. Based on these alarm levels, the intervention measures vary from physician to patient. For the physician, on the study server side, the first notification for the physician will occur at alarm level 3. This means that the alarm has to be confirmed in repeated measurements for at least 24 h. At alarm level 4, the physician will interpret the temperature data together with the patient’s past temperature recordings, foot photos (Fig. ), the interactive diary (Fig. ), medical history, and laboratory data. If the alarm is confirmed to be a true positive ulcer alarm, the physician will prescribe an intervention period via server that requires the patient to relax his foot and to reduce daily activities for five days. In the case of an assumed “false positive alarm,” the physician will reset the alarm level 4 to level 0. In contrast, on the SPDFA, the patient will be reminded to perform foot inspection and temperature measurements at every alarm level. At the respective alarm levels (1–3), the patient will receive a classification result as “uneventful.” Then, at alarm level 3, the patient will be asked to take a photo series (four images; of each foot from the plantar and dorsal sides; Fig. ). At alarm level 4, the patient will be informed that his measurements will be interpreted remotely by the physician. If the physician recommends an intervention from the server, the patient will be continuously informed to relax his foot and to reduce daily activities for five days. The patient will also be requested to confirm that he follows the advice to relax his feet and reduce daily activities with an interactive dialog and a countdown sequence. Following the five-day intervention, the physician will evaluate the collected data together with the patient’s feedback and the foot images taken on the last day during this period. Depending on this evaluation, the physician will determine whether another intervention period is required or if a doctor’s visit is needed. Control group Patients randomized to the control group will be educated for optimal foot care by a study physician at the entry into the study and will be supported on any aspects of foot care during the study course. At the study visits at 6, 12, 18, and 24 months, the same interviews and physical examinations as the intervention group will be performed to determine the foot status and possible ulcer formations. Adherence to the treatment plan For patients in the intervention groups, the transmitted data of the intelligent insole is automatically stored in the study server. If no data are collected for seven days in a row or < 17% of all measurement points within a three-month observation period, the server generates a note for the study team. Thus, it can be clarified by telephone callback or in the context of the study plan why data were not collected. Intervention provider The study coordinator and the study advisor are both physicians with > 2 years of professional experience as practicing physicians in internal medicine and diabetology. All other physicians involved in the study have professional expertise and experience in the conduct of clinical studies. The principal investigator and the study coordinator are responsible for staffing and training of the study team. All study-specific responsibilities are defined and authorized in the delegation log by the principal investigator. The training activities are documented in a training log. Outcome measures Primary outcome measure The primary outcome is occurrence of foot ulceration at any point during the 24-month study after visit 0. The severity level of foot ulcerations is classified according to the Wagner-Armstrong classification []. Any lesion will be considered as an ulcer in the sense of the primary endpoint (≥ Wagner level 1). Primary endpoints are also assessed according to time to onset of event and to the total number of events (ulceration) in the groups. Secondary outcome measures The following have been defined as secondary outcomes: Adherence to the daily two-time temperature measurement based on data acquisition with the appReport on alert frequency in the intervention group based on data acquisition with the appDetection of slow temperature drops as an indicator of blood supply disorders (at daily intervals temperature changes are recorded and evaluated by the study physician: when temperature in the forefoot or whole foot drops considerably compared to the contralateral sensor data (> 1.5 °C) and reach ambient temperature levels an additional visit to the study center will be initiated to test for changes of blood supply) safety-relevant instructions concerning diabetes, the equipment (insole) or others that are evaluated by the study protocol: frequency of AEs and SAEsPrecursors of the primary endpoint: redness, infections, or wounds in the foot area (the precursors are recorded by AEs/SAEs reports, follow-up and unscheduled visits, as well as patient’s report through photo documentation of the SPDFA)Quality of life according to the WHO-5 score [, ] at visits 1, 2, 3, and 4 Sample size Based on previously reported studies, we assumed a 20% ulcer occurrence rate over two years to be a conservative estimate for the control arm (where in case of a higher occurrence rate, the sample size becomes smaller) [, , ]. For the estimation of the treatment effect, we assumed a hazard ratio of 2.8 in accord with the study of Armstrong et al. []. Sample size calculations by use of log-rank test were based on a type I error probability of 5% (two-sided) and a power of 80%, with a drop-out rate of 20% over a two-year follow-up period per patient. This resulted in a calculated required number of cases of 147. Therefore, we plan for an inclusion of 150 patients for the intervention arm (300 patients in total). Sample size calculation was performed using the software nQuery + nTerim 4.0 (Statistical Solutions Ltd., 2015). Statistical analysis Primary endpoint The primary endpoint “time to onset of the first ulcer” will be analyzed using Cox regression for the intention-to-treat population. Regressors are the treatment arm, age (in years), gender, risk class, and degree of neuropathy. The decisive test is the test adjusted to the other influencing variables for the influence of the therapy arm (a = 0.05, two-sided). The adjusted hazard ratio of the treatment, including a 95% confidence interval, is calculated as the corresponding effect estimator. Secondary analyses pertain to the same analysis but in the per-protocol population. In addition, in the intention-to-treat population, the ulceration rates for both treatment arms and the associated odds ratio are determined using the Mantel-Haenzel test with the risk class as stratification, whereby the patients are included in the analysis regardless of the actual follow-up period. In addition, the highest Wagner classifications of an ulceration observed for each patient (possibly 0 if no ulceration) are compared between the two therapy arms using the Mann–Whitney U-test, whereby these analyses are performed separately for the two risk classes. Secondary endpoints The precursors of ulceration are analyzed analogously to the primary endpoint. The score values of the quality of life at the different time points are analyzed by means of mixed models for repeated measurements, whereby the four stratification factors from randomization (risk group, gender, age and the degree of neuropathy) are also included as influencing variables in addition to the therapy arm. The main comparison refers to the time of 24 months. AEs and SAEs are recorded separately by treatment arm and risk class. In logistic regression models, a comparison between the therapy arms (insofar as the type of AEs/SAEs is not coupled to the experimental therapy arm) is made with the occurrence of at least one event per patient as the target and the same influencing variables as in the analysis of the primary endpoint. The usage data of the insoles and the corresponding app are first extracted for the patients of the experimental arm from the automatic machine recordings and aggregated in the sense of the corresponding secondary endpoints (Prof. Dr. med. Siegfried Kropf, Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg). All analyses are carried out using the software packages SAS or SPSS. Monitoring, quality control, and data management Standard policies of the Otto-von-Guericke University Magdeburg for the development and review of the protocol will be followed, as well as policies related to adherence, safety procedures, and information management. The Trial Steering Committee will be composed of the study coordinator, co-investigators, principal investigators and the ethics committee of the Otto-von-Guericke University Magdeburg, who will provide trial oversight. According to the harmonized ICH Guideline for the EU (ICH Theme E6) [], “original data” is all information from original records and certified copies of the original records of clinical findings, observations or other activities in a study, and the necessity for the traceability and evaluation of the study. The principal investigator will provide access to original data (original records or certified copies) for all authorized persons listed in this protocol or included in the delegation log. According to our Data Monitoring Plan, we will perform quality control at multiple stages, which include: (1) the use of manuals for data collection; (2) weekly meetings with study nurses; (3) updates concerning training about protocol procedures; (4) duplicate data entries to the database; and (5) the ongoing review of the descriptive statistics for the trial data by the principal investigators with quality control review of selected data, looking for inconsistencies, missing data, and outliers. The databases will be encrypted and password-protected to ensure confidentiality. Close cooperation between the study coordinator, the data manager, and other members of the study team will be established to allow the tracking of the progress of the study to solve problems that arise during implementation and to address other issues in time. If the competent state authority or even the higher federal authority schedules an inspection, the same conditions apply as for an audit. Discussion This study makes three principal contributions concerning the prevention of DFUs. First, the introduction of sensor-equipped insoles to promote daily home-based measurements of foot temperatures. Second, the implementation of a telemedicine structure with a smartphone app to measure foot temperatures, provide photo documentation, and evaluate wellbeing (quality of life) using an interactive diary. These collected data will be transferred to a remote server for interpretation and adjustment of intervention measures. Thus, our system appears much more sophisticated and provides more reliable data compared to simple thermometric approaches. Ultimately, intelligent predictive models for DFUs will be built with the collected sensor data and interpretations, which may support medical care providers. Instead of using a thermometer (TempTouch; Xilas Medical, San Antonio, TX, USA) [, ] or thermal imaging devices (TempStatTM) [], our study innovatively introduces the sensor-equipped insole to help diabetic patients to perform daily home-based monitoring of foot temperatures. The insole can easily be inserted into house slippers or shoes and may record the temperature data continually for several hours if required. It provides a more convenient and comfortable way for frequent temperature measurements. The telemedicine structure implemented in our study comprises a remote server as core controller in the study center and the smartphone application (SPDFA) as data collecting terminal. With the SPDFA, patients can immediately comprehend the initial analysis results of their measurements. Sensor data will be transmitted from the SPDFA to the study server, together with the initial evaluations, the requested photo series (at alarm levels 3 and 4) (Fig. ), and a self-assessment about wellbeing and foot status using our interactive diary (Fig. ). Compared to the approach by Lazo-Porras et al., patients in our study do not need to identify the pre-defined alarm signs by themselves and consult the study physicians or nurses for timely interpretation []. For medical interpretation, our approach provides more information by means of photo documentation and using a wellbeing score, instead of only collecting temperature data. The study server stores the data and provides physicians with an interface to visualize the status of the patients and to interpret the ulcer alarms. In the case of a confirmed alarm, the study server can exchange data with the SPDFA to perform suitable intervention measures for the patient and to collect the patient’s interactive feedback during intervention periods. This approach will evaluate the effectiveness of activity reduction in order to delay or even avoid the development of DFU. Based on this concept, efficiency and timely interventions will be significantly improved. In addition, our alarm algorithms with stepwise graded alarm levels are able to test and verify various temperature warning measures (apart from only measuring temperature differences between left and right corresponding sensor sites) [], time intervals between two alarm levels, individual corrections based on baseline data [], or even different asymmetry thresholds []. Based on these collected data and clinical interpretations, intelligent predictive models might be built in the future for machine learning algorithms. With the development of such algorithms, intelligent telemedicine technologies have already proven to be one of the most cost-effective solutions for the early detection of DFU. As exemplified in the study of Goyal et al., deep learning methods for real-time DFU localization were applied to an extensive database of 1775 images of DFUs. The deep learning model showed great potential in the real-time localization of DFUs on an NVIDIA Jetson TX2 and a smartphone app []. The data collected in the present study will be important to test for an alarming system with a preset temperature threshold, compliance of diabetes patients to a bi-daily recording rhythm, and the challenges of picture recordings with a mobile app. Therefore, a whole package of innovation is brought to the intervention group participants; however, an entire telemedicine system with auto-response of the database recording system is not yet intended. The study physician interprets the data at 24-h intervals. In subsequent studies, we will be able to test for different thresholds concerning temperature and alarm evaluation. This will allow us to furthermore adjust algorithms to detect other temperatures abnormalities caused, e.g. by Charcot foot, or vascular insufficiency. Ultimately, machine-learning algorithms and decision tree classification will be used to train an automated predictive model of DFUs with the data that are collected in past periods. We believe that the complexity of the retrieved data from our protocol offers the potential to tackle a difficult problem from a unique aspect and, therefore, possibly will have a substantial impact on DFUs prevention not only in Germany but also in many other parts of the world. Trial status This manuscript is based on version 1.6 of the trial protocol, dated 18 February 2019. Recruitment for this study began on 30 January 2018 and should be completed by 30 December 2019. At the time of submission, our study has already recruited 196 patients; 87 patients were randomized into the intervention group. Of the 87 patients, 72 are active by daily measurements of foot temperatures with our system. The study is widely known in the area of Saxony-Anhalt; currently, a growing number of people with diabetes are eager to participate in the trial.
Hypertension in Pregnancy and Postpartum: Current Standards and Opportunities to Improve Care.	What is the age of studied population ?	test	16,770	169,256	ABSTRACT : Hypertension in pregnancy contributes substantially to maternal morbidity and mortality, persistent hypertension, and rehospitalization. Hypertensive disorders of pregnancy are also associated with a heightened risk of cardiovascular disease, and timely recognition and modification of associated risk factors is crucial in optimizing long-term maternal health. During pregnancy, there are expected physiologic alterations in blood pressure (BP); however, pathophysiologic alterations may also occur, leading to preeclampsia and gestational hypertension. The diagnosis and effective management of hypertension during pregnancy is essential to mitigate maternal risks, such as acute kidney injury, stroke, and heart failure, while balancing potential fetal risks, such as growth restriction and preterm birth due to altered uteroplacental perfusion. In the postpartum period, innovative and multidisciplinary care solutions that include postpartum maternal health clinics can help optimize short- and long-term care through enhanced BP management, screening of cardiovascular risk factors, and discussion of lifestyle modifications for cardiovascular disease prevention. As an adjunct to or distinct from postpartum clinics, home BP monitoring programs have been shown to improve BP ascertainment across diverse populations and to lower BP in the months after delivery. Because of concerns about pregnant patients being a vulnerable population for research, there is little evidence from trials examining the diagnosis and treatment of hypertension in pregnant and postpartum individuals. As a result, national and international guidelines differ in their recommendations, and more studies are needed to bolster future guidelines and establish best practices to achieve optimal cardiovascular health during and after pregnancy. Future research should focus on refining treatment thresholds and optimal BP range peripartum and postpartum and evaluating interventions to improve postpartum and long-term maternal cardiovascular outcomes that would advance evidence-based care and improve outcomes worldwide for people with hypertensive disorders of pregnancy. Key Words: blood pressure ◼ hypertension ◼ postpartum period ◼ pre-eclampsia ◼ pregnancy ◼ telemedicine Hypertension complicates 5% to 10% of all preg- nancies and is a leading cause of maternal and fetal morbidity and mortality globally.1 During the antepartum period—the time between conception and delivery—targeted hypertension management has been demonstrated to improve maternal and fetal outcomes.2–8 Postpartum blood pressure (BP) control is equally cru-cial, because the majority of hypertension-related mater- nal deaths occur after delivery, when BP peaks, and result from hypertensive complications, including stroke and cardiomyopathy.9–11 Hypertensive disorders of preg- nancy (HDP), which include gestational hypertension and preeclampsia along with chronic hypertension, are associated with a significantly elevated risk of persistent Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 491 Countouris et alhypertension and future cardiovascular and cerebrovas- cular events and mortality.12–16 To improve the short- and long-term cardiovascular health of exposed individuals, a smooth transition of care from the obstetrician to a primary care clinician or cardiologist is vital to enhance hypertension management and preventive care across the lifespan.17 Novel care models, including postpartum maternal health transition clinics, postpartum hyperten- sion clinics, and home BP monitoring programs, have emerged as strategies to overcome the often fragmented care experienced by individuals with HDP. This review provides insights into the physiologic and pathophysiologic hemodynamic alterations that affect BP during pregnancy and the postpartum period; sum- marizes unique aspects of the diagnosis and treatment of hypertension in pregnant and postpartum individuals, including safety with lactation, and the evidence behind recommendations, as well as knowledge gaps; presents an evidence-based strategy for delivering comprehen- sive postpartum hypertension care, focusing on optimiz- ing both immediate and long-term cardiovascular health through postpartum hypertension clinics and remote BP monitoring programs; and highlights differences between guidelines for the care of HDP, calling for their harmonization. PHYSIOLOGIC BP ALTERATIONS IN PREGNANCY AND AFTER DELIVERY Antepartum Regulation of BP and BP Trajectories In pregnancy, BP initially declines (Figure 1),18 following which systolic and diastolic BP progressively increase by an average of ≈8 mm Hg by the time of delivery.19 In a large international observational cohort of women at low risk of pregnancy complications, median BP was 114/70 mm Figure 1. Expected antepartum and postpartum blood pressure trajectories in a healthy pregnancy.Nonstandard Abbreviations and Acronyms ACOG American College of Obstetrics and Gynecology BNP brain natriuretic peptide BP blood pressure CHAP Chronic Hypertension and Pregnancy DBP diastolic BP HBPM home blood pressure monitoring HDP hypertensive disorders of pregnancy NT-proBNP N-terminal pro-BNP OR odds ratio SBP systolic BP SMA shared medical appointments Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTFebruary 18, 2025 Circulation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 492 Countouris et al Hypertension in PregnancyHg and 113/69 mm Hg in the first and second trimes- ters, respectively, and increased to 121/78 mm Hg at 40 weeks of gestation.19 The decline in BP is primarily due to a reduction in systemic vascular resistance, attributable to both the development of the low-resistance uteroplacen- tal circulation and to hormonal alterations mediated by progesterone and relaxin.20,21 Relaxin is initially produced by the corpus luteum and subsequently the placenta, and has been implicated as a vasodilatory pregnancy hor- mone in animal studies and human observational stud- ies.22 Among other described effects, relaxin attenuates the pressor response to angiotensin II in rats, recapitu- lating the decreased responsiveness to angiotensin II that has been described in human pregnancy.22,23 BNP (brain natriuretic peptide) and NT-proBNP (N-terminal pro-BNP), 2 hormones that function as potent vasodila- tors, are found in higher concentration during the first trimester compared with nonpregnant age-matched con- trols, implying that an increase in natriuretic peptides in early pregnancy represents an adaptive response to the physiologic volume expansion that also occurs.24 Postpartum Regulation of BP and BP Trajectories After delivery of the placenta, there is withdrawal of placentally secreted vasodilatory hormones, leading to an increase in systemic vascular resistance and a rise in BP, with peak systolic BP occurring on days 3 to 5 postpartum and peak diastolic BP occurring on days 5 to 7 postpartum.25 Additional contributors to physiologic increases in BP after delivery include rapid volume shifts and mobilization of interstitial fluid. BP should normalize by 2 weeks postpartum in individuals without HDP. PATHOPHYSIOLOGIC BP ALTERATIONS IN PREGNANCY AND AFTER DELIVERY Based on the expected decline in BP during the first 20 weeks of gestation, the classification of HDP uses this gestational age as a diagnostic marker. Any evidence of hypertension before 20 weeks of gestation is classified as chronic hypertension, and new-onset hypertension after that time is either gestational hypertension or pre- eclampsia if there is accompanying proteinuria or other evidence of target organ involvement. The fourth cate- gory of HDP is preeclampsia superimposed on chronic hypertension, which can be a challenge to diagnose in patients who have preexisting proteinuria. A growing body of evidence examining preconcep- tion and early pregnancy BP trends demonstrates that women who develop pregnancy-induced hypertension (gestational hypertension or preeclampsia) often have a blunted decline or increase in systolic BP before 20 weeks.26,27 Furthermore, a pregnant person’s BP at 20 weeks appears to be a useful means of appropriately identifying otherwise low-risk individuals who are at heightened subsequent risk of developing pregnancy- induced hypertension in a graded or “dose-dependent” fashion irrespective of BPs in very early pregnancy.28 BP trends also hold promise in differentiating individuals with chronic hypertension at heightened risk of develop- ing superimposed preeclampsia. In at-risk pregnancies, the midtrimester BP nadir occurred earlier in individuals who subsequently developed superimposed preeclamp- sia (median 21 weeks) compared with those with chronic hypertension who did not develop superimposed pre- eclampsia (median 24 weeks).29 Future work is needed to test whether the use of artificial intelligence and auto- mated analysis of BP trends in the electronic health record may allow for earlier detection of HDP. The alterations in BP trends across trimesters experi- enced by individuals with HDP are hypothesized to result from attenuated reductions in systemic vascular resis- tance and impaired tolerance to increased plasma volume. Alterations in trophoblast migration and the lack of normal spiral artery remodeling in the placenta leading to higher vascular resistance have been considered a pathophysi- ologic hallmark of preeclampsia. Additional hypothesized contributors to higher vascular resistance leading to HDP include excessive secretion of anti-angiogenic proteins (sFLt and sEng) and systemic inflammation. Furthermore, recent studies have implicated deficient natriuretic pep- tide signaling in the pathophysiology of HDP. An analysis from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) found that lower first-trimester NT-proBNP was associated with increased risk of pre- eclampsia and gestational hypertension.30 In line with these findings, genome-wide association studies have detected significant signals near the genes encoding atrial and pro-BNP and near the gene encoding natri- uretic peptide receptor C, the natriuretic peptide clear- ance receptor, with findings supporting the notion that higher genetically predicted natriuretic peptide levels are protective against HDP.31 Mendelian randomization analy- ses have lent further support to the notion that lower first- trimester natriuretic peptide levels represent a putative causal risk factor for development of HDP.32 As mentioned previously, after delivery, BP rises in the majority of postpartum individuals in the first week; how- ever, some will experience accentuated increases that cross the threshold into hypertension. This may be iat- rogenic, resulting from the administration of IV fluids or ergot derivatives for the treatment of postpartum hemor- rhage, or be a manifestation of de novo postpartum pre- eclampsia and gestational hypertension. Therefore, the risk of morbidity and mortality directly due to hypertension is highest during the first 1 to 6 days postpartum, making BP monitoring and treatment crucial during this period.11 Hypertension may persist in the postpartum period or arise de novo.33 By the second to fourth postpartum Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 493 Countouris et alweeks, BP typically stabilizes; however, many individuals will continue to have BPs ≥140/90 mm Hg, with stud- ies demonstrating 40% with BP above this threshold at 16 days postpartum and 26% above this threshold at 1 month.25,34 BP that is transiently elevated related to HDP should fully resolve by postpartum week 12. Persistently elevated BP after this period should prompt an evalu- ation of chronic hypertension and workup for potential secondary causes as clinically indicated. Individuals who are diagnosed with an HDP have an increased risk of chronic hypertension in the first year after delivery and throughout their lifespan and should have their BP moni- tored and assessed at least annually.35,36 HYPERTENSION MANAGEMENT Considerations for Pharmacologic Management of Antepartum Hypertension in Individuals With Reproductive Capability First-line antihypertensive agents, which have the most robust albeit still relatively sparse safety and efficacy data, should be prioritized, and can be used alone or in combination (Table 1). ACE inhibitors, angiotensin II re- ceptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors are contraindicated in preg- nancy due to their associations with fetal teratogenicity and oligohydramnios.37–39 Furthermore, due to concerns about teratogenicity and their effects on amniotic fluid levels, first- and second-line antihypertensive medi- cations also differ in pregnant adults compared with preferred agents for the treatment of hypertension in nonpregnant adults, although there are few studies ex- amining medications head-to-head. One reason for this deficit in evidence is that pregnant individuals are incor- rectly considered by many researchers to be a vulner- able population and thus have been underrepresented in randomized clinical trials. Pregnant individuals have the ability to give informed consent and should instead be considered a special population for better representa- tion in clinical trials.40 In alignment with recommendations from multiple societies, first-line antihypertensive medications dur- ing pregnancy include extended-release nifedipine and labetalol.37–39,41–45 Nifedipine is available in multiple for- mulations; the long-acting formulation should be used Table 1. Recommended Pharmacotherapy for the Treatment of Nonsevere and Severe Antepartum Hypertension Drug name and class Starting dose, mgMaximum daily dose, mgTitration interval in stable patients, d Special considerations Nonsevere hypertension First-line agents Nifedipine XL (calcium channel blocker)30 daily 120 or 60 BID 5–7 Contraindicated in heart failure; flushing, headache, and edema are common Labetalol (β-blocker) 200 BID 2400 2–3 Avoid in patients with bradycardia, bronchospasm, or asthma Alternative agents Methyldopa (α agonist) 250 BID 3000 2–3 Poorly tolerated: peripheral edema, dry mouth, lightheadedness, drowsiness, and effects on mood; limited availability Amlodipine (calcium channel blocker)5 daily 10 5–7 Peripheral edema is common Hydrochlorothiazide (thiazide diuretic)12.5 daily 50 3–5 Furosemide (loop diuretic) 10 daily 160 (can be BID, TID dosing)3–5 Monitor volume status to minimize risk of placental hypoperfusion Hydralazine (direct vasodilator) 10 QID 200 2–3 Carvedilol (β-blocker) 6.25 BID 25 BID (or 50 BID if weight >100 kg)2–3 Outcome data are limited in pregnancy Metoprolol tartrate (β-blocker) 12.5 BID 200 BID 2–3 Avoid in patients with bradycardia, bronchospasm, or asthma Pindolol (β-blocker) 5 BID 60 7–14 Clonidine (α agonist) 0.1 BID, or 0.1 patch weekly2.4 or two 0.3-mg patch/24 hrs7 Can have withdrawal or rebound hypertension Acute severe hypertension in pregnancy Labetalol (IV) 5–20 mg (increase every 10–15 min to max 220 mg/d) Hydralazine (IV) 5–10 mg (increase every 20 min to max 30 mg/d) Immediate release nifedipine (PO) 5–10 mg (increase every 30 min to max 50 mg/d) Labetalol (IV) 5–20 mg (increase every 10–15 min to max 220 mg/d) Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTFebruary 18, 2025 Circulation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 494 Countouris et al Hypertension in Pregnancyas a maintenance medication during pregnancy, and the short-acting formulation is reserved for rapid treatment of severe hypertension. Due to ease of once-daily admin- istration, which improves patient adherence, nifedipine is often selected as the initial treatment. For patients who experience headaches, tachycardia, or edema as a side effect, labetalol is a reasonable alternative, or it can be used in combination with nifedipine for those whose BP remains uncontrolled. Although labetalol has potential risks, such as fetal growth restriction, fetal bradycardia, and hypoglycemia, these risks are minimal and there have been no reports of teratogenicity associated with its use.46 The greatest contraindication to its use is a history of reactive airway disease. Labetalol dosing may also need to be adjusted to TID or QID due to accel- erated drug metabolism during pregnancy. There is no compelling data supporting the use of one of these agents over the other.5,47 ,48 A post hoc analysis of the CHAP trial (Chronic Hypertension and Pregnancy) did not find a difference in maternal or neonatal outcomes between patients taking labetalol compared with nifedip- ine (although medication allocation was not randomized in the trial).49 There are data from a meta-analysis dem- onstrating that β-blockers and calcium channel blockers are more effective than methyldopa for the prevention of severe hypertension.50 Methyldopa, an α2 agonist with central sympatholytic action, is another consideration for first-line therapy for hypertension in pregnancy, and is the only medication with long-term information on infant outcomes.51 In many parts of the world, methyldopa is the only available agent, and in low- and middle-income countries, its use is common, although it has fallen out of favor in high-income countries, where there may be lim- ited availability. Methyldopa may be more poorly tolerated due to its side effect profile (eg, peripheral edema, dry mouth, lightheadedness, drowsiness, effects on mood).2 Second-line pharmacologic therapies for the manage- ment of hypertension during pregnancy can be used in addition to first-line agents or as an alternative in set- tings of allergies, intolerances, or other contraindications. Of note, clonidine transdermal patch preparations can be invaluable in pregnant individuals with hyperemesis who require BP lowering, and atenolol should not be used due to risk to of fetal growth restriction. Considerations for Pharmacologic Management of Postpartum Hypertension First-line agents for the treatment of postpartum hy- pertension regardless of breastfeeding status include nifedipine, amlodipine, enalapril, and labetalol. Advan- tages of nifedipine, amlodipine, and enalapril include once-daily dosing and alignment with hypertension guidelines.39 Labetalol is commonly used to treat hyper- tension in pregnant and postpartum patients, but twice- daily or more frequent dosing is a major disadvantage. In addition, recent data suggest that labetalol may be less effective in the postpartum period compared with calcium channel blockers and may be associated with a higher risk of readmission.52 Alternative agents include diuretics, which could help early postpartum BP recov- ery after HDP.53 With diuretics, breastmilk production may be affected at higher doses. The starting and maxi- mum doses for both first-line and alternative agents are outlined in Table 2, along with lactation safety consid- erations. It is common to see mild reductions in ejection fraction (ejection fraction between 40% and 50%) associated with HDP. Although no randomized controlled trials have been done in this specific population, it is reasonable to adopt heart failure guidelines and treat hypertension with combination therapy that includes a β-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Lactation preferences will also need to be considered when choosing agents that may optimize myocardial recovery. All patients of childbearing potential with or at risk for cardiovascular disease will need counseling on and a documented plan for contraception (see following).54,55 This is particularly important for patients being initiated on an angiotensin-converting enzyme inhibitor, angio- tensin II receptor blocker, or mineralocorticoid receptor antagonist given the potential risk of teratogenicity. Approach to Antepartum Hypertension Management Severe-range hypertension (BP >159/109 mm Hg) is a medical emergency requiring confirmation of persistent elevation (usually within 15 minutes) and treatment with- in 30 to 60 minutes. Treatment should occur as rapidly as possible to reduce BP quickly and prevent maternal morbidity and mortality as well as fetal complications if the diagnosis occurs in the antenatal period. First-line therapies include intravenous labetalol or hydralazine and oral immediate-release nifedipine (in the absence of intravenous access; Table 1).38 Intravenous nitroglycerin can also be used in the treatment of severe pregnancy- induced hypertension complicated by pulmonary edema. Whereas the treatment of severe range hypertension is indicated in all situations because maternal benefits, particularly a reduced rate of intracerebral hemorrhage, outweigh potential harm, there is not a similar consen- sus when it comes to the treatment of non–severe range hypertension. In contrast to nonpregnant adults, the phar- macologic treatment of increased BP in pregnant individ- uals requires attention to balance the risks and benefits for both mother and fetus. Untreated hypertension is recognized as a substantial contributor to the increase in maternal risk, including acute kidney injury, stroke, myo- cardial ischemia, heart failure, placental abruption, and mortality. However, concerns exist regarding fetal growth Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 495 Countouris et alrestriction and stillbirth due to impaired uteroplacental blood flow with excessive BP lowering. Due to limited empiric data, the treatment of HDP is based on fewer randomized controlled trials of diagnosis and manage- ment compared with the evidence base for diagnosing and treating hypertension in nonpregnant adults and consequently there are variations in national and interna- tional guidelines.2–6 At the heart of the difference between US and international guidelines is a debate over whether trial data from one form of HDP (chronic hypertension) can be expanded and applied to the treatment of gesta- tional hypertension and preeclampsia. One of the larg- est studies of HDP management, CHIPS (Control of Hypertension in Pregnancy Study), evaluated tight con- trol (target diastolic BP, 85 mm Hg) versus less-tight control (target diastolic BP, 100 mm Hg) in patients with chronic or gestational hypertension.56 There were no significant between-group differences in the risk of pregnancy loss, high-level neonatal care, or over-all maternal complications, and less-tight control was associated with a significantly higher frequency of severe maternal hypertension. After CHIPS, the CHAP trial, a multicenter trial of 2408 pregnant individuals, randomized patients with chronic hypertension to a BP treatment goal <140/90 mm Hg versus no treat- ment unless severe hypertension (BP >160/105 mm Hg) developed.8 In the CHAP trial, treating mild chronic hypertension resulted in a statistically signifi- cant reduction in the primary composite outcome (odds ratio [OR], 0.82 [95% CI, 0.74–0.92]), which included preeclampsia with severe features, indicated preterm birth (<35 weeks), placental abruption, and fetal or neonatal death. No adverse effects on fetal growth were observed among those who received treatment, and the number needed to treat to prevent 1 primary outcome event was 14.7 . Based on these findings, the American College of Obstetrics and Gynecology (ACOG) and the Society of Maternal Fetal Medicine recommend initiation and titration of pharmacologic Table 2. Pharmacotherapy for Postpartum Hypertension Drug name and class Starting dose, mg/d Maximum dose, mg/d Lactation safety* First-line agents† Nifedipine XL (CCB) 30 120 or 60 BID Safe; RID 2.3%–3.4% Enalapril (ACEi) 5 40 or 20 BID Safe; RID 1.1% Amlodipine (CCB) 5 10 Safe; RID 1.7%–4.3% Labetalol (β-blocker) 200 TID 2400 Safe; RID 3.6% Alternative agents Hydrochlorothiazide (thiazide diuretic)12.5 50 Safe; RID 0.6%–1.2%; may decrease breastmilk production (dose >25 mg/d) Furosemide (loop diuretic) 10 160 (can be BID, TID dosing)Safe; may decrease breastmilk production (dose >20 mg/d) Hydralazine (direct vasodilator) 10 QID 200 Safe; RID 0.77%–3% Spironolactone (MRA) 12.5 NA Safe; RID 2%–4.3% Verapamil (CCB) 80 360 Safe; RID <1% Carvedilol (β-blocker) 6.25 BID 25 mg BID (or 50 mg BID if weight >100 kg)Limited safety data, likely low risk Metoprolol tartrate (β-blocker) 12.5 BID 200 BID Limited safety data, likely low risk Bisoprolol (β-blocker) 2.5 20 Limited safety data Chlorthalidone (thiazide diuretic) 12.5 100 RID 1.9%–18.1%; present in breast milk, may decrease breastmilk production Eplerenone (MRA) 25 NA RID 0.01%–3.39%; limited safety data Lisinopril (ACEi) 2.5 40 Limited safety data Losartan (ARB) 25 100 Limited safety data Valsartan (ARB) 20 320 Limited safety data Clonidine (α antagonist) 0.1 BID, or 0.1-mg patch weekly2.4 mg PO total daily, or two 0.3-mg patch/24 hrsRID 0.9%–7 .1%; limited safety data, present in breastmilk and likely negatively affects lactation CCB indicates calcium channel blocker; and MRA, mineralocorticoid receptor antagonist. Relative infant dose (RID) indicates lactational safety. RID levels <10% are considered safe. Hale’s Medications & Mothers’ Milk Online Consul- tant was used to extrapolate RID%. This resource provides RID calculations that are based on studies that consist of larger data (±AUC) and are weight-normalized (when weight is provided). If maternal weights were not published, 70 kg average body weight was used in calculations and daily milk intake of 150 mL·kg·day by infant. †In patients with mild reductions in left ventricular ejection fraction, consideration should be given for combination therapy with a β-blocker and angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTFebruary 18, 2025 Circulation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 496 Countouris et al Hypertension in Pregnancytherapy for chronic hypertension in pregnancy when BP reaches 140/90 mm Hg.8,57 Although the safety and efficacy of treating mild chronic hypertension in pregnant individuals to BP <140/90 mm Hg was demonstrated in CHAP, in the United States, guidelines have not extended this rec- ommendation to pregnant individuals with gestational hypertension or preeclampsia due to limited evidence in these populations, although practice patterns vary. Treat- ment of nonsevere hypertension has not been proven to mitigate clinical risks associated with gestational hypertension and preeclampsia, highlighting the need for further research to determine whether tighter BP goals are associated with a delay in delivery or increased maternal or fetal complications. Ongoing studies aim to provide further evidence-based guidance in this area. Most national and international guidelines are consis- tent in defining hypertension in pregnancy as systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg. However, published guidelines for the management of HDP during pregnancy vary considerably in recom- mendations for BP treatment thresholds, and are sum- marized in Table 3.38,41–45,58 To summarize, the National Institute for Health and Care Excellence and the Inter- national Society for the Study of Hypertension in Preg- nancy recommend antihypertensive treatment initiation for BP ≥140/90 mm Hg for any HDP, including ges- tational hypertension, preeclampsia, and chronic hyper- tension.41,44 ACOG recommendations differ depending on type of HDP, with a treatment threshold with main- tenance therapy of ≥140/90 mm Hg for chronic hyper- tension and ≥160/110 mm Hg for acute treatment of gestational hypertension and preeclampsia.38 The 2017 American College of Cardiology/Ameri- can Heart Association guidelines altered the threshold for the diagnosis of hypertension in nonpregnant adults to SBP >130 mm Hg or DBP >80 mm Hg.39 Although lower diagnostic BP thresholds have not been translated into obstetric practice, there is early evidence to suggest using a lower diagnostic threshold may better identify individuals at risk of preeclampsia or eclampsia compared with current BP diagnostic thresholds.59–61 In a second-ary analysis of CHAP, patients with mean BP <130/80 mm Hg (n=768) had improved perinatal outcomes com- pared with patients with BPs 130–139/80–89 mm Hg. However, these secondary analyses may be confounded by differences in comparison groups, with those achiev- ing mean BP <130/80 mm Hg more likely to be older, to be on antihypertensive medication, to be in the active treatment arm, and to have lower BP at enrollment.62 Fur- ther research is needed to determine optimal treatment goals for chronic hypertension during pregnancy and to assess the safety of targeting lower BP thresholds (eg, 130/80 mm Hg), similar to those recommended for the nonpregnant population. For patients with preeclampsia, the definitive treat- ment is frequently to deliver the fetus, and as such, pre- eclampsia is a substantial cause of iatrogenic preterm delivery. The decision to deliver is made by the obstetric or maternal fetal medicine team on the basis of several measures. Whereas uncertainty exists, close, contin- ued observation is reasonable for patients presenting with gestational hypertension or preeclampsia without severe features before 37 weeks of gestation, with deliv- ery recommended for those presenting after 37 weeks. However, for patients presenting with severe features, delivery is recommended given the high risk for rapid maternal clinical deterioration, particularly if presentation is at or beyond 34 weeks of gestation. Delivery remains the definitive treatment for pre- eclampsia with severe features, with consideration of the risks and benefits of preterm delivery. Patients pre- senting with severe features should also receive intra- venous magnesium sulfate for eclampsia or seizure prophylaxis.63 Approach to Postpartum Hypertension Management There are limited data and no guideline addressing when in the postpartum time period the diagnostic and treatment thresholds should return to those used for nonpregnant adults, although most obstetricians use up to 6 weeks as the time in which they continue to Table 3. International Society Guidelines on Diagnosis, Initiation of Treatment, and Target Blood Pressure for Nonsevere Range Hypertension in Pregnancy Guideline item AHA/ACC39ESC45ACOG/SMFM38NICE41ISHPP44SOGC42SOMANZ43 Diagnosis, mm Hg — ≥150/95; ≥140/90 ≥140 or ≥90 Medication initiation, mm Hg — ≥150 or ≥95 ≥140/90†; ≥160/110‡ ≥140 or ≥90 ≥140 or ≥90 ≥140 or ≥90 ≤135/85§ Goal BP, mm Hg — — — ≤135/85 110–140/85 DBP <85 — ACC indicates American College of Cardiology; ACOG, American College of Obstetrics and Gynecology; AHA, American Heart Association; BP, blood pressure; DBP, diastolic blood pressure; ESC, European Society of Cardiology; ISHPP, International Society for the Study of Hypertension in Pregnancy; NICE, National Institute for Health and Care Excellence; SMFM, Society for Maternal Fetal Medicine; SOGC, Society of Obstetricians and Gynecology Canada; and SOMANZ, Society of Obstetric Medicine of Australia and New Zealand. *With end-organ damage/gestational hypertension. †In chronic hypertension. ‡In gestational hypertension and preeclampsia without severe features. §In chronic and gestational hypertension. Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 497 Countouris et altreat severe range hypertension as a medical emergen- cy due to risk for postpartum preeclampsia.38 The lack of guidelines for postpartum hypertension contributes to variations in practice and inconsistent hypertension management, underscoring the need for evidence- based recommendations to address the unique risks related to elevated BP in the postpartum period. After delivery, theoretical concerns about antihypertensive medications reducing placental perfusion pressure and causing fetal harm are no longer an issue when treating maternal hypertension. At a minimum, antihypertensive medication should be initiated after delivery to treat and prevent severe hypertension, a risk factor for maternal morbidity and mortality. The threshold at which to treat hypertension varies but is widely considered to be SBP ≥ 150 mm Hg or DBP ≥ 100 mm Hg in the postpartum period.38 Many clinicians also treat postpartum individuals who develop stage 2 hypertension (BP >140/90 mm Hg) to a BP goal of <130/80 mm Hg, consistent with the 2017 American College of Cardiology/American Heart Association BP guidelines.39 This approach is also supported by recent studies demonstrating that improved postpartum BP control in the early post- partum period is associated with improved cardiac remodeling.64,65 Ongoing cohort studies and clinical tri- als are assessing the benefits of tighter BP control in the early postpartum period (Optimal Blood Pressure Treatment Thresholds Postpartum [URL: https://www. clinicaltrials.gov; Unique identifier: NCT06069102]; Intensive Postpartum Antihypertensive Treatment [URL: https://www.clinicaltrials.gov; Unique identifier: NCT05687344]; Management of Postpartum Pre- eclampsia [URL: https://www.clinicaltrials.gov; Unique identifier: NCT05775744]). Postpartum preeclampsia should be suspected in any patient with high BP combined with symptoms of persistent headache, severe abdominal pain, shortness of breath or vision changes, or SBP ≥160 mm Hg or DBP ≥110 mm Hg on 2 separate measurements taken at least 15 minutes apart. In this setting, patients should seek urgent evaluation and treated expeditiously. The transition of BP management from obstetricians to other maternal subspecialists may occur at any point; however, close communication between care teams is essential to ensure BP is monitored closely in the early postpartum period, and medications should be titrated based on results (Figures S1 and S2). Figure S3 outlines an approach to medication titration based on BP mea- surement results for the first 12 weeks postpartum. PREECLAMPSIA PREVENTION Low-dose aspirin (75 to 100 mg daily) is recommended for women with chronic hypertension, a previous history of preeclampsia, or other conditions associated with heightened risk of preeclampsia.66,67 ACOG has rec- ognized that certain high-risk populations may benefit from universal aspirin use. Aspirin should be initiated be- tween 12 and 28 weeks of gestation, optimally before 16 weeks, and continued daily until delivery. Among the evidence-based interventions for HDP, aspirin pro- phylaxis stands out as notably effective in preventing preeclampsia. In a randomized trial involving high-risk patients (n=1776), the absolute risk of preterm pre- eclampsia was significantly lower in the aspirin group (1.6%) compared with placebo (4.3%).68 This finding is further supported by meta-analyses of multiple stud- ies, showing a relative risk of 0.57 (95% CI, 0.43–0.75; P<0.001; 45 randomized controlled trials, n=20 909).69 Aspirin use during pregnancy is safe, well-tolerated, widely available, highly cost-effective, and thus univer- sally recommended. Various strategies using biomarkers (sFLt or placental growth factor) in combination with ma- ternal characteristics (mean arterial pressure and uterine artery pulsatility index) are being developed and tested to better stratify those who are at high risk for preeclamp- sia. However, large-scale randomized controlled trials have not yet demonstrated the effectiveness of these screening strategies in reducing the incidence of pre- term preeclampsia.70–72 Additional preventative therapies, including pharmacologic agents such as pravastatin, are being investigated through current clinical trials. NONPHARMACOLOGIC INTERVENTIONS Antepartum BP Monitoring Accurate BP ascertainment during pregnancy is essen- tial to prevent undertreatment and overtreatment of hy- pertension, which can harm both the mother and fetus. Out-of-office BP monitoring, which includes ambulatory BP monitoring and home BP monitoring (HBPM), offers a better reflection of BP in the natural environment. It may more accurately represent placental perfusion pres- sure and may be used to guide initiation of antihyperten- sive therapy.73 Although out-of-office BP measurements are used to monitor patients with chronic or gestational hypertension, current evidence does not show better outcomes compared with office-based measurements, and corresponding values for out-of-office normative levels have not been well described in pregnancy. The BUMP 1 and 2 studies (Blood Pressure Monitoring in High Risk Pregnancy to Improve the Detection and Monitoring of Hypertension) revealed that whereas self- monitoring was safe, it did not affect the timing of diag- nosis or control of high BP. More than half of the women in the self-monitoring group had increased BP at home ≈1 month before their clinic diagnosis, but further stud- ies are needed to evaluate the utility of out-of-office measurements for earlier diagnosis of hypertension dur- ing pregnancy.74 Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTFebruary 18, 2025 Circulation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 498 Countouris et al Hypertension in PregnancyPostpartum BP Monitoring Effect of Postpartum HBPM Programs HBPM, especially when combined with other clinical in- terventions, such as telehealth, can effectively lower BP in nonpregnant adults with hypertension.75,76 It also pro- vides an alternative to in-person postpartum BP visits, which have historically been poorly attended and drive disparate outcomes for individuals with less social sup- port and those who live in rural or underserved areas. Postpartum HBPM in the 6 weeks after delivery im- proves BP monitoring and reduces racial disparities in BP ascertainment compared with usual in-person care.77 Early identification and treatment of severe hypertension has been shown to reduce postpartum readmissions for hypertension.78,79 This effect can be cost saving, there- fore supporting wider implementation.78,80 Recent studies have shown that brief HBPM combined with medication self-management and telehealth support leads to lower BP at 6 and 9 months compared with usual postpartum care and is associated with improved measures of cardiac structure and function.64,65 If confirmed in larger studies with diverse populations, this strategy holds promise for improving longer-term cardiovascular health after HDP. Standardized treatment pathways such as those out- lined in Figures S1 through S3 can improve hypertension management and may be particularly helpful for postpar- tum patients. As discussed previously, postpartum indi- viduals have wide fluctuations in BP in the weeks after delivery, with peak postpartum SBP most frequently occurring when patients are home and often unmoni- tored.81 These BP spikes are associated with hyperten- sive crises and increased risk of stroke and heart failure, underscoring the important role of postpartum HBPM in early diagnosis and treatment to prevent adverse events.82–84 Data from the United States highlight favor- able outcomes for postpartum HBPM compared with usual care. HBPM increases postpartum BP ascer- tainment (92% versus 44%), improves postpartum visit attendance (adjusted OR, 2.30 [95% CI, 1.05–5.07]), decreases postpartum readmissions (OR, 0.5 [95% CI, 0.26–1.04]), results in fewer adverse events (OR, 0.61 [95% CI, 0.40–0.98]), and enhances transitions of care between obstetricians to cardiologists (79% versus 71%; OR, 1.50 [95% CI, 1.22–1.93]).78,85 Larger stud- ies are needed to demonstrate the effects of postpartum HBPM in improving maternal cardiovascular outcomes and mortality rates in diverse clinical settings. Protocols for HBPM Similar to HBPM in nonpregnant individuals, patient edu- cation on how to accurately measure BP for pregnant and postpartum individuals is important.86 Key elements of postpartum HBPM are summarized in Figure 2.87 Es- tablished programs have a dedicated team of clinicians, including pharmacists, nurses, and other allied health professionals, that are empowered to respond to severe hypertension alerts. It is crucial that patients use a cuff that fits properly, and when used during pregnancy or the immediate postpartum, a device specifically validated for accuracy in pregnancy (https://www.validatebp.org).88 In- surance coverage of BP devices is improving, and some patients may receive a BP measurement device during pregnancy to facilitate telemonitoring (https://www.ama- assn.org/system/files/smbp-coverage-medicaid.pdf). Figure 2. Postpartum management timeline after a hypertensive disorder of pregnancy. BP indicates blood pressure; HBPM, home blood pressure monitoring; HDP, hypertensive disorder of pregnancy; and OB, obstetrician. Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 499 Countouris et alThe recommended monitoring schedule for HBPM in the general population is 7 days and consists of 2 mea- surements taken at least 1 minute apart in the morn- ing and evening (ie, 28 readings total).86,89,90 A minimum of 3 days of monitoring is recommended (ie, 12 read- ings total). For billing purposes, patients should report a minimum of 12 BP readings within a 30-day period and a clinician should document their clinical management recommendations (https://www.ama-assn.org/system/ files/2020-06/smbp-cpt-coding.pdf). The optimal frequency and duration of HBPM for postpartum individuals has not been evaluated. Given that BP peaks at 3 to 7 days postpartum and this period of time corresponds to the highest risk of maternal stroke, ACOG recommends a BP check within 72 hours and again within 10 days of delivery.91 Successful post- partum HBPM programs have recommended checking BP daily or twice daily in the first week after discharge. One text-based program has patients check BP twice daily for 10 days.85 Other programs recommend BP monitoring 5 days a week in the first week postpar- tum, with decreasing frequency over 6 weeks of follow- up.81 Both texting and Bluetooth-enabled transmission can facilitate transfer of BP values into the electronic health record. Beyond 6 weeks, some programs further decrease frequency of monitoring to twice a week for up to 1 year postpartum. Postpartum Hypertension Clinics Postpartum maternal health transition clinics, or postpar- tum hypertension clinics, have emerged as innovative, multidisciplinary solutions to enhance the management of postpartum hypertension and improve preventive care. This review parallels the recently published American College of Cardiology Postpartum Hypertension Clinic Development Toolkit.92 Postpartum hypertension clinics can be led by a single specialty (eg, family medicine, in- ternal medicine, obstetrics, cardiology, nephrology) or as part of a multidisciplinary, collaborative cardio-obstetrics program (Figure 3).18,31–34,93–96 Postpartum hypertension clinics often use HBPM programs for monitoring and management of BP with timely, active titration of antihy- pertensive medications. In addition, these clinics provide an opportunity for screening and management of car- diovascular risk factors, including patient education on optimal lifestyle behaviors and modifications to prompt behavior change, and serve as a bridge to longitudinal care. Topics covered by the postpartum hypertension clinic should also include a debriefing of the delivery and immediate postpartum period to address residual ques- tions and trauma, an explanation of diagnoses and im- plications for short- and long-term cardiovascular and obstetric health, and the assessment and management of contraception and mental health. Clinicians should also order cardiovascular imaging studies and stress testing when appropriate. Table S1 demonstrates a checklist for how to create and sustain a postpartum hypertension clinic. Planning and engaging collaborators is the essential first step when developing a postpartum hypertension clinic. It is helpful to discuss the clinic and its inception in planning meetings to achieve support from departmental leader- ship. A needs assessment of the health care organization Figure 3. Postpartum hypertension clinic referral methods and models for clinic structure. EHR indicates electronic health record; HBPM, home blood pressure monitoring; MFM, maternal fetal medicine; and OB, obstetrician. Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTFebruary 18, 2025 Circulation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 500 Countouris et al Hypertension in Pregnancycan help identify barriers and gaps in care faced by postpartum individuals. Key collaborators should be identified and may include patients and their families, potential clinic clinicians, other clinicians providing lon- gitudinal care for postpartum patients, allied health care professionals, organizational leadership, and community members (Figure S3). Small local philanthropic or hospital- based grants can be an excellent source of funding to support the launch of a postpartum hypertension clinic. Identifying the Patient Population and Referral Models The target patient population frequently depends on the specific health care system structure and its capac- ity. Some programs refer all patients who experience an HDP; others refer only the highest-risk patients, such as those with preeclampsia with severe features or patients discharged on at least 1 antihypertensive medication. Medical staff should discuss the benefits of attending the postpartum hypertension clinic with the patient at a prenatal visit or before discharge from the delivery hos- pitalization, as this may help improve clinic attendance. Postpartum educators and navigators (eg, doulas, nurs- es, community health workers) can help identify and en- gage patients and can support scheduling appointments and initiating HBPM.97, 9 8 The clinic referral process should be integrated into a health care system’s standard peripartum care work- flow to ensure sustainability. Hosting departmental grand rounds or other educational meetings and conducting sessions with obstetrics, cardiology, internal medicine, pediatrics, family medicine, and emergency medicine can inform key clinicians who provide postpartum care about the clinic and the referral process. T ypes of referrals may include automated or default referrals, clinician-initiated referrals, and patient self- referrals. An automated referral with a visit scheduled before discharge from delivery hospitalization may sim- plify the process, increase enrollment, and improve access. Eligible patients may also be identified through systematic chart review (eg, for those who remain on antihypertensive medication in a BP monitoring pro- gram) after discharge. This may be more feasible for clinics embedded into an established BP monitoring or research program. Patient outreach may consist of a brochure given during hospitalization, a message deliv- ered as part of a BP monitoring program, or a brief video providing education and clinic information. Institutional communications teams can help develop patient-facing awareness materials. Clinic Models Postpartum hypertension clinics follow 2 general mod- els: a combined clinic model or a single specialty model (Figure 3).94–96 In the combined model, patients are seen by both cardiology/primary care/nephrology and obstet- rics/maternal fetal medicine during 1 visit. The combined postpartum hypertension clinic can be housed within a broader cardio-obstetrics clinic. In the single specialty clinic model, patients are scheduled into a dedicated postpartum hypertension clinic located within an obstet- rics, cardiology, primary care, or nephrology clinic. Multi- disciplinary clinics that use a combination of physicians, advanced practice providers, nurses, and pharmacists are preferable. A dedicated nurse or clinical pharmacist can provide additional support in seeing patients, collect- ing a medical history, adjusting antihypertensive medica- tions, and delivering patient education regarding proper BP measurement, antihypertensive medications, and risk factor modification. Types of Visits Clinics can offer in-person visits, telehealth, home visits, or shared medical appointments (SMAs). Telehealth vis- its are often desirable99 and convenient for postpartum patients and can help reduce cancellation and no-show rates.95,100–103 Clinics should prioritize telehealth visits for patients who face barriers to attending in-person visits; for example, patients with financial constraints, geograph- ic distance, transportation limitations, or limited childcare. Patients scheduled for a virtual visit should have a home BP device with an appropriately sized cuff, be instructed on proper technique, and be asked to check their BP at home before the appointment. Patients should report 1 week of at least twice-daily home BP measurements, per current guidelines, if enough time has passed since their delivery hospitalization.86 Home visits are another option. Home visits have not been well studied in the postpartum hypertension space; however, they may be more conve- nient, improve access, and reduce the need for emer- gency department visits.104 In SMA, patients are scheduled for a group visit that includes both individual patient encounters (for medica- tion titration, results review, and ordering of testing) and a group educational program.105,106 SMA sessions have an added benefit of providing a sense of community for par- ticipants. The SMA model requires a space with a confer- ence or meeting room for group education and areas for individual examinations. As an alternative, SMAs could be conducted through telehealth with separate breakout rooms for individualized management. Timing and Content of Visits Optimal visit timing will depend on the goals of the clinic, staffing model, and patient needs and preferences. Re- ferrals are accepted at any point postpartum in most programs. Early postpartum visits (within 2 weeks) focus primarily on early BP management and medication titra- tion (Figure 2). ACOG recommends a BP check and visit within 3 to 10 days of delivery for high-risk individuals,38 followed by a comprehensive postpartum visit between 4 and 6 weeks after delivery. Later postpartum visits (2 weeks to 1 year postpartum) focus on BP management, lifestyle optimization, cardiovascular risk assessment, Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 501 Countouris et aland transition to primary care. Additional clinical activi- ties are outlined in Figure 4. Patients living in 1 of the 4 states without Medicaid expansion beyond 6 weeks postpartum may benefit from visits scheduled within 6 weeks of delivery.107 Follow-up visits depend heavily on local capacity and patient acuity. All patients with HDP should follow longitudinally with a primary care clinician. For patients without an established source of primary care, a warm handoff to a primary care clinician may improve transi- tions of care. If patients have an indication for subspe- cialty care, they can follow-up in a specialty clinic (eg, cardiology, nephrology, obstetrics).KEY CONSIDERATIONS AFTER HDP Contraception Discussion of and provision of effective contraception in the postpartum period is strongly recommended to avoid unintended pregnancies and short interpregnan- cy intervals, and essential for patients being prescribed teratogenic medications. Contraception options are divided into tiers based on their efficacy rate. Long- acting reversible options of intrauterine and subder- mal implants carry the lowest failure rate of <1% with typical use.108 As such, they are strongly recommend- ed for appropriate candidates given their excellent Figure 4. Postpartum hypertension clinic activities. ASCVD indicates atherosclerotic cardiovascular disease; CRP, C-reactive protein; CTA, computed tomography angiography; GAD-7 , Generalized Anxiety Disorder–7; PHQ-9, Patient Health Questionnaire–9; and PREVENT, Predicting Risk of Cardiovascular Disease Events. Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTFebruary 18, 2025 Circulation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 502 Countouris et al Hypertension in Pregnancyefficacy and safety in patients with hypertension. Oth- er effective options for individuals who wish to avoid any future pregnancies include tubal ligation or male sterilization. The next tier of contraceptive agents have failure rates between 6% and 12% and include combined hormonal contraceptive pills, progestin-only pills, transdermal patches, vaginal rings, diaphragms, and depot medroxyprogesterone injection.109 There is an absolute contraindication to combined hormonal contraceptive pills and transdermal patch use in indi- viduals with uncontrolled hypertension (BP >160/110 mm Hg),54 and caution should be exercised when us- ing combined hormonal contraceptive pills in individu- als with hypertension (BP ≥ 140/90 mm Hg). There is also an increased risk of thromboembolism with com- bined hormonal contraceptive pills, transdermal patch, and vaginal ring among those with hypertension, to- bacco use, or age ≥ 35 years. The lowest tier includes barrier methods, spermicide, and natural family plan- ning, which have the highest failure rates, between 18% and 28%.55 Pregnancy and Delivery Debriefing Individuals with HDP often deliver preterm and may have traumatic birth experiences. The postpartum hy- pertension clinic can provide a space to debrief the delivery and subsequent complications related to HDP. Fetal or neonatal complications should be acknowl- edged, including neonatal intensive care unit admis- sion. Clinicians should be sensitive to the possibility of perinatal demise, and, when appropriate, inquire about the neonate’s health. Clinicians should provide compas- sionate communication and supportive care during the postpartum period. Screening for Mental Health Conditions Screening for depression, anxiety, and other mental health conditions in all individuals in the postpartum pe- riod is critical to ensure appropriate diagnosis and treat- ment. The incidence of postpartum depression (major depression lasting at least 2 weeks) is as high as 14%.110 Screening can be performed using the Edinburgh Post- natal Depression Scale.111 Patients with a positive screen should be referred to behavioral health specialists for further management. Risk of Recurrence Many individuals who are seen in a postpartum hyper- tension clinic have unanswered questions about future pregnancy risk. The risk of recurrence is directly related to the severity of the incident case, the gestational age at onset, and medical comorbidities.112 For individuals with a history of a HDP, low-dose aspirin should be adminis-tered in subsequent pregnancies starting at 12 weeks to reduce the risk of preeclampsia.113 CONCLUSIONS HDPs are an important public health concern due to their strong association with maternal and fetal or neo- natal morbidity and mortality. Effective BP management during pregnancy and postpartum is essential to improve outcomes among these dyads and requires careful se- lection of pharmacologic interventions and close moni- toring of BP and symptoms. Cardiovascular clinicians play a central role in BP and cardiovascular prevention care after an HDP, with innovative strategies such as HBPM and postpartum hypertension clinics support- ing optimized postpartum health. Telehealth, including HBPM, can help reduce disparities in postpartum care. The field of HDP has historically been one with a limited evidence base, and although research has accelerated, many evidence gaps remain. Future research should prioritize determining optimal treat- ment thresholds, assessing the safety profiles of antihypertensive medications, and understanding their effects on maternal and neonatal outcomes to advance evidence-based care for pregnant individu- als with hypertension (Figure 5). Over the past decade, as data in the nonpregnant population have emerged that lower BP targets are generally associated with improved outcomes, there has been a similar shift in the recognition of the detrimental effects of permis- sive hypertension in pregnancy and its association with adverse maternal and fetal outcomes.3,105 This review highlights the need for trials to readdress the current thresholds used to define hypertension in pregnancy to improve the detection of HDP and reduce hypertensive complications in pregnancy. Upcoming clinical trials will examine the effect of tighter BP control in the postpar- tum period, and future longitudinal studies are needed to assess the influence of these care models on both short- and long-term cardiovascular outcomes in this high-risk population. In contrast to other cardiovascular conditions, where there is considerable agreement among recommenda- tions, international guidelines for HDP recommend var- ied treatment approaches despite being based on the same sparse clinical evidence. This review underscores the need for augmentation of the evidence base and harmonization of guideline recommendations across organizations to improve care through consistent mes- saging to patients and clinicians. Future guideline recommendations must also account for worldwide dif- ferences in maternal health care access and resources to maximize the feasibility and generalizability of recom- mendations for the achievement of equity in maternal and fetal care. Downloaded from http://ahajournals.org by on February 19, 2025 STATE OF THE ARTCirculation. 2025;151:490–507 . DOI: 10.1161/CIRCULATIONAHA.124.073302 February 18, 2025 Hypertension in Pregnancy 503 Countouris et alARTICLE INFORMATION Affiliations Department of Medicine, Division of Cardiology (M.C.), University of Pittsburgh (A.H.), PA. Department of Medicine, Division of Cardiology, Washington Univer- sity in St Louis, MO (Z.M., K.E.W.). Renal-Electrolyte and Hypertension Division, Department of Medicine (J.B.C.), Department of Biostatistics, Epidemiology, and Informatics, and Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (J.B.C.). Department of Medi- cineand Obstetrics and Gynecology, Division of Cardiovascular Sciences, Uni- versity of South Florida Morsani College of Medicine, Tampa General Hospital Heart and Vascular Institute (D.C.). Department of Obstetrics and Gynecology and Medicine, Division of Maternal Fetal Medicine & Cardiology, University of California, Irvine (A.B.H.). Department of Medicine, Division of Cardiology, Wom- en’s Heart Health Program, Massachusetts General Hospital, Boston (C.M.H., M.C.H., A.S.). Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine (A.H.), and Brown University Health Cardiovascular Institute (K.S.), Alpert Medical School of Brown University, Providence, RI. Department of Medicine, Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN (K.L.). Department of Medicine, Division of Cardiology, University of Califor- nia San Francisco (M.M.M.). American Medical Association, Chicago, IL (N.S.). Center for Women’s Reproductive Health (R.S., A.T.) and Department of Obstet- rics and Gynecology (R.S., A.T.), University of Alabama at Birmingham. Depart- ment of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle (E.Y.). Department of Cardiovascular Medicine, Heart Vascular Thoracic Institute at the Cleveland Clinic, OH (L.C.). Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (N.A.B.). Atria Institute, New York, NY (N.A.B.). Acknowledgments This paper was produced from the American College of Cardiology Reproductive Health and Cardio-Obstetrics Section and the American College of Cardiology Cardiovascular Disease in Women Writing Committee. Sources of Funding None.Disclosures Dr Sarma is a consultant for Pfizer. Dr Honigberg reports consulting fees from Comanche Biopharma, advisory board service for Miga Health, site principal in- vestigator work for Novartis, and research support from Genentech. Dr Yang is an advisory board member for Idorsia, Mineralys, Qure.ai, and Sky Labs; consults for Genentech; and receives honoraria from the American College of Cardiology and research grants from Microsoft Research. Dr Harrington is a consultant for Pfizer and Always. Dr Sachdev is an employee of the American Medical Association. The views expressed in the article are those of the authors and may not neces- sarily reflect the official position of the American Medical Association. The other authors report no disclosures or conflicts of interest. Supplemental Material Figures S1–S3 Table S1
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the age of studied population ?	The age of the studied population is not explicitly mentioned in the context; it can be inferred to include adults undergoing emergency endodontic treatment for irreversible pulpitis in mandibular molars.	41,103	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the outcome of the study ?	"Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser mais bem investigados para a adoção de parâmetros em prol de seu emprego definitivo."	41,104	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the studied population ?	"pacientes com pulpite irreversível em molares mandibulares buscando atendimento de urgência."	41,105	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the number of the studied population ?	18 estudos para soluções anestésicas; 10 estudos para condutas alternativas.	41,106	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the study design of this article ?	"uma revisão sistematizada da literatura."	41,107	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the condition of the studied population ?	"pulpite irreversível em molares mandibulares."	41,108	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the studied or evaluated intervention ?	"soluções anestésicas e condutas alternativas."	41,109	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the studied indication ?	"manejo de molares inferiores com pulpite irreversível."	41,110	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Neurophysiol. 1998;79(4):1746 -54. 8- Roy M, Nakanishi T. Differential properties of tetrodotoxin -sensitive and tetrodotoxin -resistant sodium channels in r at dorsal root ganglion neurons. J Neurosci. 1992;12(6):2104 -11. 9- Hargreaves KM, Keiser K. Local anesthetic failure in endodontics: mecha nisms and management. Endod Topics. 2002;1(1):26 -39. 10- Sampaio RM, Carnaval TG, Lanfredi CB, Horliana AC, Rocha RG, Tortamano IP. Comparison of the anesthetic efficacy between bupivacaine and lidocaine in patients with irreversible pulpitis of mandibular molar. J Endod. 2012;38(5):594 - 7. 11- Ashraf H, Kazem M, D ianat O, Noghrehkar F. Efficacy of articaine versus lidocaine in block and infiltration anesthesia administered in teeth with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2013;39(1):6 -10. 12- Parirokh M, Yosefi MH, Nakhaee N, Abbott PV, Manochehrifar H. The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What are the comparators ?	"lidocaína vs bupivacaína; lidocaína vs articaína; diferentes técnicas anestésicas complementares."	41,111	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What did improve quality of live ?	A context does not explicitly mention what improved quality of life; it can be inferred that improved anesthetic success may enhance patient comfort during treatment.	41,112	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . 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A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Any adverse events or complications reported ?	"Não foram relatados eventos adversos ou complicações."	41,113	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What are the primary outcomes ?	"soluções anestésicas e condutas alternativas."	41,114	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What are the secondary outcomes ?	A contextual informação não menciona desfechos secundários.	41,115	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . 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A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Was the magnitude of the treatment effect observed clinically significant ?	A magnitude do efeito do tratamento não é explicitamente discutida em termos de significância clínica; entretanto, alguns métodos alternativos mostraram melhorias nas taxas de sucesso anestésico.	41,116	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Has a statistical analysis of the data been provided and is it appropriate ?	"Sim, os estudos revisados forneceram análises estatísticas, e o contexto discute a significância estatística dos achados de forma apropriada."	41,117	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . 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A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	What is the target device ?	"Não aplicável; o estudo não foca em um dispositivo específico."	41,118	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Was the device used for the same intended use (e.g., methods of deployment, application, etc.) ?	"Não aplicável; o estudo não envolve um dispositivo."	41,119	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Was the data generated from a patient group that is representative of the intended treatment population e.g., age, sex, etc.) and clinical condition (i.e., disease, including state and severity) ?	"Sim, os dados foram gerados a partir de pacientes diagnosticados com pulpite irreversível em molares mandibulares buscando atendimento de urgência, representando a população de tratamento pretendida. Detalhes específicos sobre idade e sexo não são fornecidos."	41,120	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. 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J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . 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A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Was the data Bench Simulation ?	"Não, os dados foram provenientes de ensaios clínicos envolvendo pacientes humanos."	41,121	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Do the reports or collations of data contain sufficient information to be able to undertake a rational and objective assessment ?	"Sim, o contexto indica que tabelas comparativas e resultados detalhados dos estudos incluídos foram fornecidos, permitindo uma avaliação racional e objetiva."	41,122	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Do the outcome measures reported reflect the intended performance of the device ?	"Não aplicável; o estudo não envolve um dispositivo."	41,123	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the Population as nominals .i.e give short answers	"pacientes com pulpite irreversível em molares mandibulares em atendimento de urgência."	41,124	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the Indication as nominals .i.e give short answers	"manejo de molares mandibulares com pulpite irreversível."	41,125	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. 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J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the Comparators as nominals .i.e give short answers	"lidocaína vs bupivacaína vs articaína; técnicas alternativas como anti-inflamatórios, crioterapia."	41,126	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the Outcomes as nominals .i.e give short answers	"sucesso anestésico medido pela dor durante abertura coronária e/ou instrumentação dos canais radiculares."	41,127	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . 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A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the Study Type as nominals .i.e give short answers	"revisão sistematizada da literatura."	41,128	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . 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A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. 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Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the target devices as nominals	"Nenhum dispositivo alvo."	41,129	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155 -60. 13- Allegretti CE, Sampaio RM, Horliana AC, Armonia PL, Rocha RG, Tortamano IP. Anesthetic Efficacy in Irreversible pulpitis: a randomized clinical tria l. Braz Dent J. 2016;27(4):381 -6. 14- Visconti RP, Tortamano IP, Buscariolo IA. Comparison of the anesthetic efficacy of mepivacaine and lidocaine in patients with irreversible pulpitis: a double -blind randomized clinical trial . J Endod. 2016;42(9):1314 -9. 15- Aggarwal V, Singla M, Miglani S. Comparative evaluation of anesthetic efficacy of 2% lidocaine, 4% articaine, and 0.5% bupivacaine on i nferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double -blind clinical trial . J Oral Facial Pain Headache. 2017;31(2):124 -8. 16- Rogers BS, Botero TM, Mcdonald NJ, Gardner RJ, Peters MC. Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double -blind study. J Endod. 2014;40(6):753 -8. 17- Shapiro MR, Mcdonald NJ, Gardner RJ, Peters MC, Botero TM. Efficacy of articaine versus lidocaine in supplemental infiltration for mandibular first versus second molars with irreversible pulpitis: a prospective, randomized, double - blind clinical trial . J Endod. 2018;44(4):523 -8. 18- Aggarwal V, Singla M, Miglani S, Kohli S. E fficacy of articaine versus lidocaine administered as supplementary intraligamentary injection after a failed inferior alveolar nerve block: a randomized double -blind study . J Endod. 2019;45(1):1 - 5 19- Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversible pulpitis . J Endod. 2015;41(9):1408 -11. 20- Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS. Does the volume of supplemen tal intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized - double blind clinical trial. Int Endod J. 2018;51(1):5 -11. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 15 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 21- Silva SA, Horliana ACRT, Pannuti CM, Braz -silva PH, Bispo CGC , Buscariolo IA, et al. Comparative evaluation of anesthetic efficacy of 1.8 mL and 3.6 mL of articaine in irreversible pulpitis of the mandibular molar: a randomized clinical trial. PLoS One. 2019;14(7):e0219536. 22- Pereira LA, Groppo FC, Bergamaschi CDEC, Meechan JG, Ramacciato JC, Motta RH, et al. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects. Oral Surg Oral Med Or al Pathol Oral Radiol. 2013;116(2):85 -91. 23- Aggarwal V, Singla M, Saatchi M, Hasija M. Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior a lveolar nerve block: a randomized double -blind study. Acta Odontol Scand. 2020;78(4):275 -80. 24- Kreimer T, Kiser R, Reader A, Nusstein J, Drum M, Beck M. Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):598 -603. 25- Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate -buffered lidocaine on the success of inferior alveolar nerve block for teet h with symptomatic irreversible pulpitis: a prospective, randomized double -blind study. J Endod. 2015;41(1):33 -5. 26- Shadmehr E, Aminozarbian MG, Akhavan A, Mahdavian P, Davoudi A. Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis. Int Endod J. 2017;50(6):531 -9. 27- Mousavi SA, Sadaghiani L, Shahnaseri S, Zandian A, Farnell DJJ, Vianna ME. Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with sy mptoms of irreversible pulpitis: a prospective, randomized clinical trial. Int Endod J. 2020;53(2):145 -53. 28- Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients wit h irreversible pulpitis. J Endod. 2010;36(3):379 -82. 29- Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36(9):1450 -4. 30- Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565 -9. 31- Akhlaghi NM, Hormozi B, Abbott PV, Khalilak Z. Efficacy of ketorolac buccal infiltrations and inferior alveolar nerve blocks in patients with irreversible pulpitis: a prospective, double -blind, randomized clinical trial. J Endod. 2016;42(5):691 - 5. 32- Saha SG, Jain S, Dubey S, Kala S, Misuriya A, Kataria D. Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, double -blind, randomized controlled clinical tria l. J Clin Diagn Res. 2016;10(2):25 -9. 33- Saatchi M, Farhad AR, Shenasa N, Haghighi SK. Effect of sodium bicarbonate buccal infiltration on the success of inferior alveolar nerve block in mandibular first molars with symptomatic irreversible pulpitis: a prospective, ra ndomized double -blind study . J Endod. 2016;42(10):1458 -61. Lucas Nunes Cechin et al. 16 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 34- Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with ir reversible pulpitis: a prospective, randomized, controlled, double -blind study . Bull Tokyo Dent Coll. 2017;58(4):231 -6. 35- Topçuoğlu HS, Arslan H, Topçuoğlu G, Demirbuga S. The effect of cryotherapy application on the success rate of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis . J Endod. 2019;45(8):965 -9. 36- Aksoy F, Ege B. Efficacy of submucosal tramadol and lidocaine on success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis. Odontology. 2020;108(3):433 -40. 37- Aggarwal V, Singla M, Saatchi M, Gupta A, Hasija M, Meena B, et al. Preoperative intraligamentary injection of dexamethasone can improve the anesthetic success rate of 2% lidocaine during the endodontic management of mandibular molars with symptomatic irreversible pulpitis . J Endod. 2021;47(2):161 -8. 38- Vieira WA, Paranhos LR, Cericato GO, Franco A, Ribeiro MAG. Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? A systematic review and meta -analysis. Int Endod J. 2018;51(10):1104 -17. 39- Nagendrababu V, Pulikkotil S, Suresh A, Veettil S, Bhatia S, Setzer F. Efficacy of local anaesthetic solutions on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a systematic review and network meta - analysis of randomized clinical trials. Int Endod J. 2019;52(6):779 -89. 40- Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double -blind clinical trial. Journal of Endodontics. 2011;37(12):1603 -7. 41- Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31(1):36 -40. 42- Corbella S, Taschieri S, Mannocci F, Rosen E, Tsesis I, Del Fabbro M. Inferior alveolar nerve block for the treatment of tee th presenting with irreversible pulpitis: a systematic review of the literature and meta -analysis. Quintessence Int. 2 017;48(1):69 -82. 43- Zanjir M, Lighvan N, Yarascavitch C, Beyene J, Shah P, Azarpazhooh A. Efficacy and safety of pulpal anesthesia strategie s during endodontic treatment of permanent mandibular molars with symptomatic irreversible pulpitis: a systematic review and network meta -analysis . J Endod. 2019;45(12):1435 -64. 44- Malamed SF, Tavana S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compend Contin Educ Dent. 2013;34(1):10 -20. 45- Brkovic B, Todorovic L, Stojic D. Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery. Int J Oral Maxillofac Su rg. 2005;34(4):401 -6. 46- Sivaramakrishnan G, Alsobaiei M, Sridharan K. Interventions for anesthetic success in symptomatic irreversible pulpitis: a network meta -analysis of randomized controlled trials. J Dent Anesth Pain Med. 2019;19(6):323 -41. 47- Tupyota P, Chailertvanitkul P, Laopaiboon M, Ngamjarus C, Abbott PV, Krisanaprakornkit S. Supplementary techniques for pain control during root Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 17 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 canal treatment of lower posterior teeth with irreversible pulpitis: A systematic review and meta -analysis. Aust Endod J. 2018;44(1):14 -25. 48- Miura T. Direction of strategic use: a new classification of non -steroidal anti - inflammatory drugs based on reactivity with peroxidase. Yakugaku Zasshi. 2013;133(6):681 -9.
Efficacy of anesthetic solutions and different clinical approaches for the management of lower molars with irreversible pulpitis: review of the literature	Extract the follow-up duration from the study, distinguishing different subgroups if necessary. If different follow-up periods are reported, list them separately.	"A duração do acompanhamento não é especificada no contexto."	41,130	182,811	ABSTRACT Aim: Anesthetic difficulties may arise from scenarios of infection and inflammation, as in cases of irreversible pulpitis. Therefore, the purpose of this systematized review was to help the clinician to achieve deep anesthesia during emergency endodontic treatm ent of mandibular molars with irreversible pulpitis. Materials and methods: Randomized clinical trials performed with patients with irreversible pulpitis in mandibular molars seeking emergency care were selected via PubMed. These should assess anesthetic success by reporting pain during coronary opening and/or instrumentation of r oot canals. Two distinct primary outcomes were the target of this study (anesthetic solutions and alternative approaches). For anesthetic solutions, 18 studies were included, and for alternative conducts, 10 studies. Literature review: Several strategies h ave been investigated to increase the percentage of anesthetic success, such as the use of complementary techniques to inferior alveolar nerve block (IANB), increasing the volume of anesthetic or vasoconstrictor, tamponade of solutions and alternative appr oaches. Discussion: It was found that there is no difference in the success rate for the IANB and for complementary anesthetic techniques for the different anesthetic agents. In addition, higher adrenaline concentration, increased volume of solution used, substances capable of buffering the anesthetic solution, administration or injection of anti -inflammatories, cryotherapy and nitrous oxide also seem to improve anesthetic success rates. Conclusion: Several alternative methods seem promising to potentiate d eep anesthesia, and should be better investigated for the adoption of parameters in favor of its definitive use. Keywords: Endodontics. Anesthesia . Mandibular nerve . Preanesthetic medication . Lucas Nunes Cechin et al. 4 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 INTRODUÇÃO Os principais critérios que influenciam a avaliação de um Cirurgião -Dentista por parte do paciente são sua capacidade de control ar a dor e de realizar anestesias sem grandes desconfortos1. Satisfazer este aspecto, mantendo em boas condições a relação profissional -paciente, pode se tor nar um enorme desafio ao clínico despreparado para a resolução de casos complexos de anestesia local. Mesmo para muitos endodontistas experientes, as dificuldades anestésicas mais desafiadoras podem decorrer de cenários de infecção e inflamação, como são o s casos de pulpit e irreversíve l2. Conquistar anestesia profunda de forma rápida e com confiança em um dente agudamente inflamado é um trabalho árduo3. Sabe -se que para impedir a propagação do impulso nervoso, a forma não ionizada do anestésico local precisa adentrar a membrana plasmática das células neurais e, dessa forma, bloquear seus canais de sódio. No entanto, a inflamação e a infecção diminuem o pH tecidual, retardando o início da anestesia e interferindo no bloqueio nervoso, pois quanto mais ác ido for o meio em que o anestésico é depositado, menor será a disponibilidade de sua forma não ionizada capaz de se difundir para o interior do nervo4. Ademais, em uma pulpite irreversível, o tecido está banhado em exsudatos inflamatórios, os quais além de diminuírem o limiar de excitabilidade do nervo, fazem com que os vasos sanguíneos estejam dilatados, causando mais rapidamente a eliminação do anestésico do local de injeção5. Estudos em ratos auxiliam na explicação sobre a dificuldade aumentada de aneste siar dentes com pulpite aguda6-8. Estes trabalhos sugerem que as fibras C dos nervos sensitivos, que estão relacionadas à dor excruciante e espontânea, característica da pulpite irreversível, são mais resistentes aos anestésicos que as outras fibras. Os es tudos ainda citam que alguns canais de sódio (Na+) dessas fibras apresentam resistência à ação da lidocaína, levando a maiores dificuldades em obter completa an estesia das mesmas6,7. Além disso, há indícios que a inflamação estimula a neoformação de canais de sódio resistentes à tetrodotoxina (TTXr) no tecido pulpar, os quais são resistentes à ação dos anestésicos locais8. Dessa forma, o objetivo deste trabalho é revisar na literatura disponível os melhores agentes anestésicos, as melhores concentrações de vasoconstritor, a adição de substâncias às soluções e condutas clínicas alternativas que auxiliem o Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 5 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Cirurgião -Dentista a realizar, de maneira mais confortável para o paciente, o tratamento endodôntico de urgência de molares mandibulares sob anestesia prof unda e efetiva. MATERIAIS E MÉTODOS Este estudo é uma revisão sistematizada da literatura que utilizou a base de dados PubMed para a seleção de artigos científicos relevantes ao objetivo do trabalho. Buscas na literatu ra A pesquisa pelos artigos foi realizada através do uso dos termos “local anesthesia”, “molar” e “irreversible pulpitis”, utilizando o descritor booleano “AND”. Uma busca manual nas referências dos resultados obtidos na busca eletrônica também foi realizada. Ao fim, a busca resultou em 74 estudos . Dois desfechos primários distintos eram alvo deste estudo (soluções anestésicas e condutas alternativas). Para soluções anestésicas, foram incluídos 18 estudos, e para condutas alternativas , 10 estudos. Critérios d e inclusão Para ambos os desfechos f oram incluídos ensaios clínicos randomizados em humanos, redigidos na língua inglesa, publicados a partir do ano de 2010, onde os pacientes tivessem necessariamente sido diagnosticados com pulpite irreversível em molar mandibular e sua urgência tivesse sido realizada sob anestesia durante a execução da pesquisa. Os estudos deveriam avaliar o sucesso anestésico através do relato de dor durante as etapas de abertura coronária e/ou instrumentação dos canais radiculares util izando a escala visual analógica. Cada desfecho foi avaliado individualmente juntamente dos critérios acima elencados , nos estudos recuperados na busca. Critérios de ex clusão Foram excluídos trabalhos em que os pacientes apresentassem radiolucidez no periápice do dente a ser tratado ou em que os pacientes apresentassem dentes superiores envolvidos, e aqueles que, durante sua leitura, acabaram mostrando não aludir ao tema pesqui sado. Lucas Nunes Cechin et al. 6 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Triagem Dois pesquisadores (L.N.C., I.B.C.), independentemente, avaliaram os títulos/resumos pelos critérios de inclusão e exclusão em ‘excluir’, incluir’ e ‘incerto’. Após, os artigos classificados como inclusos e incertos foram selecionados para leitura na íntegra pelos mesmos pesquisadores, de forma independente. Discrepâncias na triagem de títulos/resumos e artigos em texto completo foram resolvidas por meio de discussão. Em caso de discordância, foi obtida a opinião de um terceiro revisor (G.P. ). Mapeamento Tabelas comparativas foram construídas a partir dos estudos incluídos, com a extração das seguintes informações: autor (ano), objetivo (comparação) e resultados . REVISÃO DE LITERATUR A Na tentativa de bloquear o nervo alveolar inferior, grandes dificuldades são experienciadas pelo Cirurgião -Dentista , principalmente quando se trata de dentes agudamente inflamados9. Ao investir em tornar essa anestesia mais pre visível, surgem questões como : qual solução anestésica utilizar? O volume da injeção altera o sucesso da anestesia? A adição de complementos na solução pode aumentar a previsibilidade para o bloqueio do nervo alveolar inferior ( BNAI ) e anestesias complementares em dentes irreversivelm ente inflamados? Tabelas comparativas entre os estudos incluídos foram elaboradas para elucidar a questões acima listadas. Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 7 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Agente anestésico em anestesia primária Tabela 1 - Eficácia de diferentes soluções anestésicas em técnicas primárias de anestesia. Autor (Ano) Objetivo (Comparação) Resultados Sampaio et al.10 (2012) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Ashraf et al.11 (2013) Lidocaína versus articaína em BNAI e em IM por V Não houve diferença estatisticamente significativa para o BNAI. Articaína foi superior para a IM por V Parirokh et al.12 (2015) Lidocaína versus bupivacaína em BNAI Não houve diferença estatisticamente significativa Allegretti et al.13 (2016) Lidocaína versus mepivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas Visconti et al.14 (2016) Lidocaína versus mepivacaína em BNAI Mepivacaína foi superior Aggarwal et al.15 (2017) Lidocaína versus bupivacaína versus articaína em BNAI Não houve diferenças estatisticamente significativas BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular Agente anestésico em anestesia complementar Tabela 2 - Eficácia de diferentes soluções anestésicas em técnicas complementares de anestesia. Autor (Ano) Objetivo ( Comparação) Resultados Rogers et al.16 (2014) Lidocaína versus articaína em IM por V complementar ao BNAI Articaína foi superior Shapiro et al.17 (2018) Lidocaína versus articaína em IM por V, complementar ao BNAI Não houve diferenças estatisticamente significativas para os primeiros molares Aggarwal et al.18 (2019) Lidocaína versus articaína em IL complementar ao BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar Lucas Nunes Cechin et al. 8 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Volume de solução administrada Tabela 3 - Eficácia de diferentes volumes de solução anestésica administrada em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Abazarpoor et al.19 (2015) Um versus dois tubetes de articaína em BNAI Dois tubetes foi superior Aggarwal et al.20 (2018) 0,2 ml versus 0,6 ml de lidocaína em IL complementar ao BNAI 0,6 ml foi superior Silva et al.21 (2019) Um versus dois tubetes de articaína em BNAI Não houve diferença estatisticamente significativa BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar Concentração de adrenalina Tabela 4 - Eficácia de diferentes concentrações de adrenalina em diversas técnicas anestésicas. Autor (Ano) Objetivo ( Comparação) Resultados Pereira et al.22 (2013) 1:100.000 versus 1:200.000 de adrenalina com articaína em IO Não houve diferença estatisticamente significativa Aggarwal et al.23 (2020) 1:80.000 versus 1:200.000 de adrenalina com lidocaína em IL complementar ao BNAI 1:80.000 foi superior BNAI: bloqueio do nervo alveolar inferior IL: anestesia intraligamentar IO: anestesia intraóssea Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 9 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Adição de substâncias à solução anestésica Tabela 5 - Eficácia da adição de substâncias à solução anestésica. Autor (Ano) Objetivo ( Comparação) Resultados Kreimer et al.24 (2012) Adição de manitol à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Saatchi et al.25 (2015) Adição de bicarbonato de sódio à lidocaína em BNAI Não foi capaz de aumentar as taxas de sucesso significativamente Shadmehr et al.26 (2017) Substituição da adrenalina por clonidina no uso de lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso Mousavi et al.27 (2020) Adição de sulfato de magnésio à lidocaína em BNAI Foi capaz de aumentar as taxas de sucesso BNAI: bloqueio do nervo alveolar inferior Condutas alternativas Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (continua) Autor (Ano) Objetivo ( Comparação) Resultados Oleson et al.28 (2010) Administração de ibuprofeno prévio ao BNAI Não aumentou as taxas de sucesso Parirokh et al.29 (2010) Administração de ibuprofeno ou de indometacina previamente ao BNAI Ambas as medicações foram capazes de aumentar as taxas de sucesso Stanley et al.30 (2012) Administração de óxido nitroso previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Akhlaghi et al.31 (2016) IM por V com cetorolaco de trometamina após o BNA I Foi capaz de aumentar a taxa de sucesso Saha et al.32 (2016) Administração de cetorolaco de trometamina ou de diclofenaco potássico previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso. O cetorolaco de trometamina foi superior ao diclofenaco potássico Saatchi et al.33 (2016) IM por V com bicarbonato de sódio previamente ao BNAI Foi capaz de aumentar a taxa de sucesso Lucas Nunes Cechin et al. 10 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 Tabela 6 - Eficácia de diferentes condutas previamente ou após o momento anestésico. (conclusão ) Autor (Ano) Objetivo (Comparação) Resultados Bidar et al.34 (2017) Administração de ibuprofeno ou de dexametasona previamente ao BNAI As duas medicações foram capazes de aumentar as taxas de sucesso Topçuoğlu et al.35 (2019) Administração de crioterapia após o BNAI Foi capaz de aumentar a taxa de sucesso Aksoy e Ege36 (2020) IM por V com tramadol após o BNAI Não foi capaz de aumentar a taxa de sucesso Aggarwal et al.37 (2021) IL com diclofenaco sódico ou com dexametasona previamente ao BNAI A dexametasona foi capaz de aumentar a taxa de sucesso BNAI: bloqueio do nervo alveolar inferior IM: infiltração mandibular V: vestibular IL: anestesia intraligamentar DISCUSSÃO Os resultados do presente estudo revelam a inexistência de superioridade anestésica da articaína e da bupivacaína sobre a lidocaína na técnica do BNAI10-13,15. Em linha antagônica, u m estudo anterior relatou superioridade para a mepivacaína na comparação com a lidocaína no BNAI14, e outro estudo , embora sem diferença estatística, também relatou uma tendência maior de sucesso a mepivacaína13. No entanto, uma revisão sistemática prévia com metanálise , que incluiu estudos com baixo risco de viés38, demonstrou não haver diferenças significativas entre mepivacaína e a lidocaína nas taxas de sucesso do BNAI. Em contradição a esses achados, outra revisão sistemática com metanálise39 apresentou resultados superiores para a articaína e para mepivacaína sobre a lidocaína. Todavia, esses achados foram encontrados na metanálise geral, sendo que quando se realizou a metanálise somente dos estudos com baixo risco de viés, também não foi obse rvado diferença entre as soluções. Portando, é coerente supor que não há diferença nas taxas de sucesso no BNAI entre mepivacaína e a lidocaína, uma vez que a compilação dos ensaios clínicos randomizados de alta qualidade suporta esse achado. Com relação as técnicas complementares ao BNAI, não houve diferença nas taxas de sucesso entre a articaína e a lidocaína na técnica IL18. Já para a técnica IM, Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 11 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 um estudo16 relatou superioridade para a articaína, e outro estudo17 relatou taxas similares entre lidocaína e articaína. É presumível assumir que esse conflito de resultados possa estar relacionado com questões metodológicas. Um estudo iniciou o acesso à câmara pulpar 5 minutos após a anestesia16, ao passo que o outro estudo, 15 minutos após17. A articaína tem capacidade de se difundir com maior facilidade através de osso cortical40, sendo está uma possível justificativa de sua superioridade com apenas 5 minutos de espera para o acesso endodôntico. Já em 15 minutos, é lógico imaginar que ambas as soluções já ten ham exercido seus mecanismos de ação, e portanto, por isso não foi observado diferenças significativas entre ambas. Embora a escolha do agente anestésico não tenha alterado os resultados do uso da complementação com IL, a concentração de adrenalina parece interferir nos resultados desta técnica. A maior concentração de adrenalina foi capaz de aumentar a capacidade desta técnica de anestesiar profundamente o s dente s com polpa inflamada23. Esse aumento também foi observado ao aumentar o volume de solução anestésica utilizada20. Outras considerações sobre o volume anestésico empregado podem ser realizadas ao avaliar a efetividade da utilização de mais de 1 tubete anestésico ao realizar o BNAI. O senso comum entre os clínicos dita que a utilização de maiores volumes de solução anes tésica em casos de inflamação em dentes mandibulares é conduta indispensável para anestesia profunda. Esse pensamento pode ser explicado pelo alto tempo de latência existente para que uma anestesia pulpar seja obtida na mandíbula após bloqueios nervosos ma ndibulares. Desta forma, resultados similares poderiam ser obtidos ao se esperar o tempo necessário para o anestésico atingir o efeito desejado, tempo este que pode, ainda, variar de paciente para paciente41. Os 2 estudos incluídos nesta revisão sobre o te ma em questão resultaram em aumento da taxa de sucesso anestésico aumentando de 1 para 2 tubetes o volume de solução administrada em BNAI19,20, embora 1 dos estudos não tenha obtido diferenças estatisticamente significativas21. É importante salientar que revisões sistemáticas com metanálise prévias42,43 não encontraram vantagens em aumentar o volume anestésico e citam que existem condutas alternativas mais efetivas para alcançar anestesia profunda. A eficácia da adição de substâncias ao tubete anestésic o também foi testada em 4 diferentes estudos24-27. Resultados positivos foram encontrados para a adição de sulfato de magnésio, manitol e bicarbonato de sódio à lidocaína em BNAI, embora o bicarbonato de sódio não tenha obtido diferenças estatisticamente Lucas Nunes Cechin et al. 12 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 significativas24,25,27. Dessa forma, a utilização de substâncias capazes de tamponar a solução anestésica parece promissora, uma vez que a solução anestésica tamponada pode aumentar o conforto durante a injeção, diminuir o tempo de latência44 e supostamente, aumentar a efetividade clínica. Além disso, a substituição da adrenalina por clonidina ao se utilizar lidocaína em BNAI também atingiu maiores taxas de sucess o26. A clonidina é um agente agonista seletivo dos receptores α-2 utilizado como a nti-hipertensivo central na medicina, com seu potencial de melhorar anestesias já relatado anteriormente em cirurgia de terceiros molares45. Os resultados encontrados nesta revisão dão suporte a administração de anti - inflamatórios esteroidais e não -esteroi dais previamente ao tratamento de urgência endodôntica29,32,34. Estes resultados estão de acordo com o encontrado em diferentes revisões sistemáticas com meta -análise42,43,46,47. Sabe -se que os anestésicos locais têm seu efeito limitado perante a diminuiçã o do limiar de excitabilidade dos nociceptores devido aos efeitos dos mediadores inflamatórios presentes na polpa dental irreversivelmente inflamada9. Portanto, a ação benéfica dos medicamentos deve -se as ações dos anti -inflamatórios esteroidais sobre o ácido araquidônico ou dos anti-inflamatórios não esteroidais sobre as ciclo -oxigenases , as quais estão diretamente relacionadas em impedir os efeitos da cascata de inflamação , que tem como produto a liberação de mediadores inflamatórios48. Além disso, algu ns estudos desta revisão incluíram a possibilidade da injeção d e anti-inflamatórios, resultando em efeitos positivos no aumento da taxa de sucesso anestésico em um menor intervalo de tempo previamente ao procedimento e logo após a administração do anestési co local31,36,37. Em consonância, a injeção de bicarbonato de sódio33, a crioterapia35 e o óxido nitroso30 também se mostraram uma ótima alternativa . É evidente que a presente revisão apresenta algumas limitações. Primeiro, embora somente ensaios clínicos randomizados foram incluídos, existem variações metodológicas entre eles, fato esse, que leva à heterogeneidade e que limita a comparação exata entre os estudos. Em segundo lugar, por se tratar de uma revisão sistematizada, não foi realizada uma avaliação de risco de viés dos estudos incluídos, sendo essa análise possível de se realizar no futuro durante uma revisão sistemática completa. Diante do exposto , a presente revisão identificou que não há diferença na taxa de sucesso no BNAI e para técnicas anestésicas complementares para os diferentes agentes anestésicos, exceto, a técnica IM após o BNAI com uso de articaína e espera Eficácia de soluções anest ésicas e diferentes condutas clínicas para o manejo de molares inferiores com pulpite irreversível: uma revisão sistematizada da literatura 13 Revista da Faculdade de Odontologia de Porto Alegre, v. 64, e 128114 , jan./dez. 2023 de apenas 5 minutos para acesso a câmara pulpar , que se mostrou mais eficaz na anestesia profunda. Além disso, a maior concent ração de adrenalina , o aumento do volume da solução utilizada , substâncias capazes de tamponar a solução anestésica, a administração ou injeção de anti -inflamatórios, a crioterapia e o óxido nitroso também parecem melhoram as taxas de sucesso anestésico da polpa severamente inflamada . Por fim, os estudos futuros devem se concentrar em padronizar questões metodológicas na busca por resultados mais sólidos e fidedignos, e estabelecer parâmetros precisos para o uso clínico das condutas alternativas, visando um emprego seguro e preciso de sua associação com os agentes anestésicos . CONCLUSÃO Embora os estudos incluídos tenham certa heterogeneidade, tratam -se de ensaios clínicos randomizados, os quais tem como característica um alto nível de evidência, devido ao processo de randomização, e controle de possíveis variantes. Dessa forma, os achados suportam que para o BNAI não há uma solução anestésica que se sobressaia em casos de molares inferiores com pulpite irreversível. Diversos métodos alternativos parecem promissores para potencializar uma anestesia profunda, e devem ser melhor investigados para a adoção de parâmetros em prol de seu emprego definitivo. CONFLITO DE INTERESSES Os autores declaram não haver conflito de interesses. REFERÊNCIAS 1- DE ST Georges J. 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Basic concepts in facial and neck thread lifting procedures.	What is the condition of the studied population ?	Not applicable; the article does not focus on the condition of a specific population but discusses facial and neck tissue sagging related to aging.	51,956	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Basic concepts in facial and neck thread lifting procedures.	What is the studied or evaluated intervention ?	The studied or evaluated intervention is facial and neck thread lifting procedures, including techniques like V, U, and I using floating type threads.	51,957	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Basic concepts in facial and neck thread lifting procedures.	What is the studied indication ?	The studied indication includes addressing skin and connective tissue sagging associated with the progression of aging.	51,958	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Basic concepts in facial and neck thread lifting procedures.	What are the comparators ?	Comparators are not explicitly mentioned; however, the article compares traditional cadaver studies and dissections with modern ultrasound-guided assessments.	51,959	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Basic concepts in facial and neck thread lifting procedures.	What did improve quality of live ?	Improvement in the quality of threads manufactured by thread lifting companies and the introduction of diverse thread designs improved the quality of live procedures.	51,960	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Basic concepts in facial and neck thread lifting procedures.	Any adverse events or complications reported ?	Yes; adverse events or complications such as parotid gland and duct complications are referenced in the cited studies (e.g., Reference 2 and 12).	51,961	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Basic concepts in facial and neck thread lifting procedures.	What is the age of studied population ?	Not explicitly mentioned; the article is a review of thread lifting procedures and does not involve a specific studied population.	51,951	194,671	INTRODUCTION In the case of thread lifting, addressing the lateral face, which is not significantly correlated with facial expressions in a fundamen- tal sense, could adequately be managed using conventional concepts from existing literature.1However, ensuring comfort related to facial expressions became imperative, necessitating procedures that do not cause discomfort. Particularly for individuals of Asian descent who have prominent cheekbones, the difficulty in accessing the angle between the lateral and anterior faces posed a consistent challenge during procedures, prompting contemplation of various methods to resolve these shortcomings. In recent years, the improvement in the quality of threads manufactured by thread lifting companies, along with the introduction of diverse designs, has contributed to mak- ing thread lifting procedures more efficient and yielding superior outcomes compared to the past. In terms of the anatomical aspects of thread lifting, previ- ously, understanding the relationship between the actual position of Gi-Woong Hong and Soo-Bin Kim contributed equally as the first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.threads during procedures and the surrounding structures necessi- tated cadaver studies and dissections. However, nowadays, the uti- lization of ultrasound has facilitated a more convenient means of verifying procedural outcomes. Consequently, after attempting a more diverse array of procedures during treatments, it has become possi- ble to assess the results to some extent without directly resorting to cadaver dissections. This development has significantly influenced the enhancement of procedural methods by enabling a more objec- tive evaluation of outcomes, without the need to directly examine cadaveric specimens.2,3 The primary objective of thread lifting is often associated with addressing skin and connective tissue sagging that occurs with the pro- gression of aging. Traditionally, there has been a tendency to approach facial aging as a universal sagging of any facial structure following the aging process.4However, the authors argue that fibrous tissues commonly referred to as retaining ligaments in the face do not uni- formly succumb to aging but instead maintain their form and strength, contributing to differential effects on various facial regions.5 Hence, it is crucial to consider the varying strength of these retaining ligaments, as this disparity can lead to differences in skin Skin Res Technol. 2024;30:e13673. wileyonlinelibrary.com/journal/srt 1o f5 https://doi.org/10.1111/srt.136732o f5 HONG ET AL . and tissue sagging across facial areas.5Understanding these differ- ences is essential to efficiently enhance skin and tissue sagging. It involves determining the appropriate plane for inserting threads, uti- lizing resilient tissues, and identifying lax tissues to address facial aging mechanisms effectively. In discussing procedural techniques, authors aim to explore mech- anisms that are challenging to resolve through thread lifting, such as sagging tissues. The review will elucidate how specific types of threads can be used to address these issues and describe approaches to improving different facial regions, considering anatomical consider- ations alongside practical concepts. Rather than focusing on specific techniques commonly used or indi- vidual instructions for various brands of threads in general thread lifting procedures, the review emphasis is on exploring the general mechanisms of action concerning how threads impact tissues during thread lifting. 1.1 Definition of the terms In the context of performing thread-lifting procedures, it is important to initially address the terminology associated with the procedure. When explaining the types of threads utilized, the procedural tech- niques, and the mechanisms involved in thread lifting, a range of terminologies is employed beyond medical terms relating to anatomi- cal structures. In this regard, authors aim to elucidate the significance of the terminologies used in our practice, examining whether these terms hold specific meanings or if there are instances of misapplication within the field. The primary reason notwithstanding, our skin and connective tis- sues undergo a loss of elasticity and supportive strength with aging, resulting in deepening wrinkles and tissue sagging in the direction of gravity. The primary objective of thread lifting can be described as uti- lizing threads extensively to pull and secure these sagging tissues in the opposite direction of gravity, preventing their re-sagging.6 The commonly used straight or moderately long floating-type threads, also known as floating threads, play a pivotal role in this task.7 Their protrusions grip onto the lax tissues and are responsible for pulling these tissues in the opposite direction from where they are hanging. Additionally, these threads need to be skillfully placed on the opposite side of the lax tissues to prevent them from falling due to tis- sue loads. The action of threads’ protrusions gripping onto the tissues is referred to as “anchoring.” Through this anchoring action, the loose tissues below are captured by the protrusions of the threads, termed as the “hanging point.” Conversely, areas where the protrusions of the threads are caught in firm tissues are commonly referred to as the “fixing point.”8 Therefore, in thread lifting using these protrusion threads, the most critical aspect is the strength of their ability to firmly grasp onto tissues, known as “anchoring strength.” Once the tissues are firmly gripped by the protrusions, the threads need to withstand the load applied by the tissues and external forces to maintain their anchored position. The force applied by the tissues to revert to their original state whileTABLE 1 The mechanical properties of threads encompass various attributes, notably the definitions of tensile, anchoring, and holding strength. Definition Tensile strengthTensile strength is gauged by the duration a thread remains intact when subjected to tension force, indicating the force that both holds and pulls the ends of the thread on either side. Anchoring strengthAnchoring strength signifies the force at which the cog of a thread firmly attaches to the tissue, facilitating the function of pulling and gathering tissue. It involves the cog effectively catching and securing the tissue in place. Holding strengthHolding strength refers to the capability to sustain forces once the cogs are securely embedded in the tissue, enabling the exertion of force to pull and gather tissue without release. being held by the threads’ protrusions is termed “stress.” Overcoming this stress, along with the threads’ ability to endure and maintain their position, is referred to as “holding.” To ensure long-lasting procedural effects, the holding strength of these protrusions, signifying the force they withstand to maintain their position, also needs to be substantial. Previously, there was a tendency to equate anchoring strength and holding strength, assuming that if the protrusions adhered well to tis- sues, they would maintain their position effectively. However, in the current landscape, where thread manufacturing methods have diver- sified, with variations in protrusion shapes, positions, directions, and quantities, it is imperative to differentiate and consider both forces separately (Table 1).10–13 1.2 Lateral facial lifting (short or medium-length I-type bidirectional cogged threads) In Figure 1, the area where the cogged protrusions of the I-shaped bidi- rectional thread attach mainly to the lax tissues below is designated as the “hanging point,” while the region where the thread’s protru- sions catch onto the firmer tissues above is termed the “fixing point.” Though some refer to this phenomenon as “adhesion” instead of “fix- ing,” due to the sensation that the threads adhere firmly to tissues, the term “fixing point” is commonly used among medical practition- ers to prevent confusion. Irrespective of whether the direction of the protrusions is bidirectional or multidirectional, when using any type of thread, the thread pulling and securing the lax tissues upward should remain fixed and firmly adhered to the upper firm tissues without mov- ing downward. The essential force required here is the “anchoring and holding strength” of the upper protrusions, which need to endure and maintain their position within the firmer tissues, signifying the loca- tion where the threads are anchored. To achieve authentic fixation, it would necessitate either securing the threads tightly to the tissues at the base using pins or other means. Consequently, the term “fixing point” we use does not solely imply the degree of attachment or forceHONG ET AL . 3o f5 FIGURE 1 Design of short or medium-length I-type bidirectional cogged threads (A). The thread depicted in the image is the Secrete line Illusion (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). exerted by the protrusions attaching to the lax tissues below; instead, it predominantly signifies the firm adherence of the upper tissue-bound protrusions, capable of withstanding significantly greater force. Thus, when inserting straight cogged threads through one upper puncture site, then intertwining and burying the threads emerging from the entry site rather than simply cutting them, it does not strictly equate to securing the threads in place. By interconnecting the protrusions on both sides using straight cogged threads or double-needle multidi- rectional threads, it strengthens the fixing point, allowing the threads on the sides to assist each other in better withstanding the downward force caused by the lax tissues held by the protrusions, enhancing the fixing point. This technique, often referred to as “suspension,” high- lights the role of the middle section where the threads are intertwined and suspended between the protrusions on either side, emphasizing the consolidation of the threads to fortify the fixing point. 1.3 Lateral facial lifting (long length cannula guided U-type cogged threads) Similarly, there is a practice among some individuals to refer to a 40 cm or longer cannula-guided bidirectional cogged thread, often termed as a fixed type thread. When applied in a U-shaped manner around the zygomatic area, the rationale for directing its central section through the thick deep temporal fascia is to prevent a chiseling effect, wherein the central portion, subject to the weight of the tissues held by the protrusions of both threads, might gradually fray and tear due to the load-bearing effect. The force applied to seemingly immobilize the thread in place prevents the chiseling effect. This force is the result of the opposing actions of the forces exerted by the protrusions of both threads. The force tending to descend through the forward motion of the left thread’s protrusion is counteracted by the reverse force of the right thread’s protrusion, and vice versa. Thus, the forward and reverse forces exerted by the protrusions of the left and right threads counteract each other, creating an appearance of the thread being FIGURE 2 Design of long-length cannula-guided U-type cogged threads (A).The thread depicted in the image is the Secrete line Double S Miracle (B, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). firmly fixed. However, it is essential to note that the central part of the long thread is not truly fixed within the firm tissues of the zygo- matic area. Nevertheless, to best withstand the load of the lax tissues held by the lower protrusions, reinforcing the fixing point is essential by ensuring that the upper protrusions closer to the zygomatic area are firmly anchored in the firmer tissues, enabling them to withstand the weight below, ensuring the stability of the upper protrusions without movement (Figure 2). 1.4 Lateral facial lifting (long length double needle V-type cogged threads) The same principle applies when utilizing V-shaped or L-shaped double-needle long bidirectional cogged threads without a central pro- trusion. Fundamentally, these threads differ primarily in how they are applied—whether using a cannula to insert the thread or directly inserting it with a needle, along with variations in the length of the central section without protrusions. Consequently, the sensation of the threads not moving within the tissues actually arises from the opposing forces exerted by the forward and reverse directions of the protrusions on the opposite sides, acting in an alternating manner. However, due to the absence of a lengthy central non-protruding section, the insertion of these threads typically involves using two entry sites to place the thread through considerably thick tissues, rather than burying it through a single-entry site. Similarly, ensuring that the protrusions nearer to the entry site are firmly lodged within robust tissue helps counteract the opposing forces generated by the weight of the tissues hanging on the lower protrusions, enhancing the fixing point. This fortification aims to withstand the forces and maintain stability for the upper protrusions without displacement (Figure 3). 1.5 Thread lifting for double chin (long length cannula guided or double needle cogged threads) In the context of cogged thread procedures, the consistency of tissues engaged by the threads proves to be a more critical factor than the4o f5 HONG ET AL . FIGURE 3 Design of long-length double needle V-type cogged threads. The thread depicted in the image is the Secrete line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). FIGURE 4 Design for double chin improvement of long-length cannula guided or double needle cogged threads. The thread depicted in the image is the Secrete Line Double S Miracle and Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). direction of the threads themselves. Even with the same type of cogged thread, variations in the firmness of tissues traversed by the threads influence the location of the fixing point. This mechanism becomes apparent when using elongated bidirectional cogged threads measur- ing more than 40 cm, particularly when employing a lengthy I-shaped configuration rather than the U or V shapes in the submental area, as depicted in Figure 4. Upon creating an entry site at the central point, elongated bidirectional cogged threads are introduced bilater- ally in an extended I-shape manner, with both ends maneuvered to FIGURE 5 U-shape design for double chin improvement of long-length cannula-guided cogged threads. The thread depicted in the image is the Secrete Line Illusion (Hyundai Meditech., Inc., Wonjusi, Republic of Korea). traverse the firm tissues below the ears. As previously expounded, the opposing directions of the cogged threads on both sides counterbal- ance each other, exerting forces primarily on the ends of the thread engaged with the firm tissues instead of the central part, as observed in U or V-shaped configurations. Consequently, the threads attached to the outer firm tissues act akin to a fixing point, securing the threads and exerting traction on the central section, thereby compressing the loose and irregular tissues hanging in between, thus ameliorating the appearance of the submental area. 1.6 Thread lifting for double chin (U-shape design for double chin improvement of long length cannula guided cogged threads) The same principle applies when employing elongated U-shaped bidi- rectional cogged threads in the submental area and similarly in the central region of the neck using a U-shaped thread configuration with the absence of a central cog. When inserting threads in such a design, positioning the middle of the thread without cogs facing outward, the ends of the thread, rather than the central part, act as the fixing point. Consequently, the force exerted on the ends of the thread results in an equivalent compression of the irregular central area of the neck, confirming a comparable effect (Figure 5). 2 DISCUSSION The advancement of thread lifting procedures has brought about considerable enhancements in addressing facial sagging, primarilyHONG ET AL . 5o f5 associated with aging. Particularly in the lateral face region, indepen- dent of facial expressions, the conventional concepts established in the existing literature are often deemed adequate.14–17However, the necessity to ensure comfort related to facial expressions has become paramount, warranting procedures that minimize discomfort.18For individuals of Asian descent with prominent cheekbones, accessing the angle between the lateral and anterior faces during procedures posed persistent challenges, prompting the exploration of diverse methods to address these limitations. The recent advancements in thread qual- ity thread lifting companies, coupled with the introduction of varied designs, have significantly contributed to the increased efficacy of thread lifting procedures compared to previous practices. The primary objective of thread lifting predominantly revolves around addressing skin and connective tissue sagging associated with aging. It has been customary to view facial aging as a universal sagging process affecting all facial structures. In conclusion, this review delves into the core and general thread lifting procedures, emphasizing the critical role of tissue consistency, anchoring strength, and holding strength. ACKNOWLEDGMENTS This study was conducted in compliance with the principles set forth in the Declaration of Helsinki. There is no financial disclosure to report. CONFLICT OF INTEREST STATEMENT I acknowledge that I have considered the conflict-of-interest state- ment included in the “Author Guidelines.” I hereby certify that, to the best of my knowledge, that no aspect of my current personal or profes- sional situation might reasonably be expected to significantly affect my views on the subject I am presenting. DATA AVAILABILITY STATEMENT No.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the outcome of the study ?	"He then underwent open cystolitholapaxy given the inability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube."	40,879	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the studied population ?	"A 59-year-old man with a history of schizophrenia, diabetes, hypertension, antibiotic resistant urinary tract infection, urethra stricture requiring suprapubic catheter, and vesiculo-cutaneous fistula"	40,880	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the number of the studied population ?	"1"	40,881	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the study design of this article ?	"Case report"	40,882	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the condition of the studied population ?	"Suprapubic catheter dysfunction secondary to bladder stone encasement"	40,883	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the studied or evaluated intervention ?	"Open cystolitholapaxy"	40,884	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the studied indication ?	"Management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction"	40,885	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What are the comparators ?	"None"	40,886	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What did improve quality of live ?	"Not explicitly mentioned in the context"	40,887	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Any adverse events or complications reported ?	"Yes; complications included bladder stone encrustation causing catheter occlusion, urinary retention, skin irritation, overgranulation"	40,888	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What are the primary outcomes ?	"Not explicitly mentioned in the context; inferred as resolution of catheter obstruction and urinary retention"	40,889	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What are the secondary outcomes ?	"None"	40,890	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Was the magnitude of the treatment effect observed clinically significant ?	"Not explicitly mentioned; however, the successful removal of the stone and restoration of catheter function indicates clinical significance"	40,891	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Has a statistical analysis of the data been provided and is it appropriate ?	"No statistical analysis was provided"	40,892	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the target device ?	"Suprapubic catheter"	40,893	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Was the device used for the same intended use (e.g., methods of deployment, application, etc.) ?	"Yes"	40,894	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Was the data generated from a patient group that is representative of the intended treatment population e.g., age, sex, etc.) and clinical condition (i.e., disease, including state and severity) ?	"Data was generated from a single patient; representativeness to broader population is not applicable"	40,895	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Was the data Bench Simulation ?	"No"	40,896	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Do the reports or collations of data contain sufficient information to be able to undertake a rational and objective assessment ?	"Yes"	40,897	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Do the outcome measures reported reflect the intended performance of the device ?	"Yes"	40,898	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the Population as nominals .i.e give short answers	"59-year-old male with schizophrenia, diabetes, hypertension, antibiotic resistant UTI, urethral stricture"	40,899	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the Indication as nominals .i.e give short answers	"Distal urethral obstruction; chronic urinary retention due to bladder dysfunction"	40,900	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the Comparators as nominals .i.e give short answers	"None"	40,901	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the Outcomes as nominals .i.e give short answers	"Catheter removal; bladder stone removal; resolution of urinary retention"	40,902	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the Study Type as nominals .i.e give short answers	"Case report"	40,903	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the target devices as nominals	"Suprapubic catheter"	40,904	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	Extract the follow-up duration from the study, distinguishing different subgroups if necessary. If different follow-up periods are reported, list them separately.	"Not reported"	40,905	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Handbook of Occupational Therapy for Adults with Physical Disabilities	What is the age of studied population ?	"59-yea-old"	40,878	149,879	Introduction Suprapubic catheterization is relatively common in the management of patients with distal urethral obstruction or chronic urinary retention due to bladder dysfunction. It is an effective and well tolerated proce- dure, carries lower rates of infections and higher satisfaction levels among patients in comparison to urethral catheterization [ 1-3]. How- ever, there are associated complications that can arise with this tech-nique, especially without appropriate follow up care. Acute urinary retention is an emergent condition that requires im- mediate attention. Frequently, patients present to the emergency de- partment (ED) in need of assistance due to urinary catheter malfunction. Causes of catheter dysfunction include balloon irritation, altered mental status, infection, fecal impaction, tube obstruction, im- proper sizing, improper positioning of the catheter and others [ 4]. This case report describes a man diagnosed with a bladder stone encasinghis suprapubic catheter that was removed surgically and replaced with a functioning catheter. 2. Case report A 59- year-old man with a history of schizophrenia, diabetes, hyper- tension, antibiotic resistant urinary tract infection, urethra stricture re- quiring suprapubic catheter, and vesiculo-cutaneous ﬁstula presented to the ED with a nonfunctioning suprapubic catheter. Due to his baselinecognitive impairment the patient resided in a group home and had anassigned guardian to make his medical decisions. The patient reportedthat his urinary catheter had not functioned properly for about a month and that it stopped draining completely two hours prior to his arrival. He did not know when his provider had last exchanged the catheter. On his arrival, his heart rate was 101 beats per minute. His blood pressure, oxygen saturation, temperature and respiratory rate were within normal limits. He was alert and at his mental status baseline with normal heart and lung sounds. His abdomen was mildly distended and mildly tender to palpation in the suprapubic region without re- bound or guarding. At the site of the suprapubic catheter, clear yellow urine was leaking around the site of the catheter with mild excoriation of the super ﬁcial soft tissue surrounding the stoma. There was no urine draining from the catheter. As mentioned, the patient had alongstanding history of vesiculo-cutaneous ﬁstulas which were visible on examination in the perineum with excoriation of the surroundingskin. Due to urinary obstruction and retention, the emergency provider attempted to ﬂush the catheter but met resistance. Serum laboratory testing showed no leukocytosis, no acute kidney injury and were overall reassuring. Urinalysis was not obtained in the ED as urine was not collected. A CT scan of the abdomen and pelvis with IV contrast demonstrated a suprapubic catheter in place with ex- tensive circumferential calci ﬁcation around the balloon and the distal tip (Fig. 1 A,B). There were multiple bladder stones measuring greater than two centimeters and urethral stones. The urology service was consulted, and the patient was seen in the ED. The urology team knew the patient; he was intermittently lost to follow-up and likely had maintained his suprapubic catheter for several months. They also could not ﬂush the catheter and found the balloon of the catheter to be ruptured. Thus, they could not remove the suprapubic tube. The urology team counseled the patient on options and his guard- ian gave consent. He then underwent open cystolitholapaxy given theAmerican Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 ∗Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States. E-mail addresses: nsullivan@mfa.gwu.edu (N. Sullivan), Pourmand@gwu.edu (A. Pourmand). https://doi.org/10.1016/j.ajem.2022.03.0310735-6757/© 2022 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajeminability to access his bladder via his urethra as well as size of the stones. During the procedure, surgeons removed the stone intact along with the suprapubic tube. The stone had occluded the catheter preventing drain- age and causing urinary retention ( Fig. 2 ). The patient tolerated the pro- cedure well. Patient subsequently was discharged with urologyoutpatient follow up.3. Discussion This report describes a rare ﬁnding of a suprapubic catheter enveloped by a bladder stone that caused the tube to occlude. This case illustrates the possibility of further complication when chronic indwelling catheters are not exchanged on schedule particularly in patients at increased risk of bladder calculi. It encourages providers tohave a high index of suspicion for the possibility of catheter encrusta- tion in cases of acute or subacute retention in a patient with a chronic indwelling catheter. Compared to urethral catheterization, suprapubic catheterization presents a greater risk of blockage and insertion failures; insertion of a suprapubic catheter requires specialized training and the procedure carries a 1 –3% risk of bowel injury. However, they have lower rates of urinary tract infection, scrotal infection, urethral damage, and scrotalerosion and patient discomfort [ 1,5]. A scoping review suggests urethral catheters may be associated with a higher rate of upper urinary tractcomplications as well [ 6]. In this case, the patient's history of extensive urethral stricture made suprapubic catherization a superior option. Acommon but less severe complication of suprapubic catheters appears to be skin irritation secondary to leakage at the insertion site [ 6]. Overgranulation may also occur [ 1]. Both of these complications were present in our patient and may have been exacerbated by the fact that urine leaked around the obstructed catheter as the patient retained urine. Bladder calculi are most often associated with patients with spinal cord injury but may occur in other circumstances as well [ 7-9]. In this patient population, urinary tract infections and indwelling cathetersare associated with increased risk of bladder calculi [ 7]. Historically, there has been con ﬂicting evidence whether long term catheters themselves cause bladder calculi formation [ 9-12 ]. The mechanism for encrustation has been attributed to the formation of bio ﬁlms on catheters [ 13]. Research suggests that any increase in bladder calculi formation is indiscriminate of the type of catheter [ 1,6]. One study showed the annual risk of calculi formation may be as high as 16% in those patients who previously formed one stone. While there does not appear to be an exact consensus on the recommended frequency of catheter changes, more frequent catheter changes in patients with recurrent bladder calculi decrease the risk of encrustation [ 8,13]. While our patient did not have a spinal injury, he had several risk factors for encrustation including recurrent urinary tract infections, chronic indwelling catheter, infrequent changes and prior history of calculi formation. He had missed several appointments for reevaluation and catheter exchange. Furthermore, as some urine was able to leak around the catheter, his caretakers did not quickly recognize his retention. 4. Conclusion Occlusion of the distal catheter secondary to encrustation is a rare complication of suprapubic catheter dysfunction. Providers should have a higher index of suspicion particularly in patients with urinary catheters that have been in place for greater than a month, in patients with a history of bladder stones and in those with inconsistent follow up to care. Immediate surgical intervention is indicated for acute reten- tion with a non-functioning catheter that cannot be addressed in the ED. Conﬂict of interest The authors do not have a ﬁnancial interest or relationship to disclose regarding this research project. Financial support This is a non-funded study, with no compensation or honoraria for conducting the study. Fig. 1. A. and B shows the excised urinary catheter with a distal tip that is encased in a large bladder stone (arrow). Fig. 2. The stone had occluded the catheter preventing drainage.N. Sullivan, R. AlRemeithi and A. Pourmand American Journal of Emergency Medicine 56 (2022) 395.e5 –395.e7 395.e6Credit authorship contribution statement Natalie Sullivan: Conceptualization, Writing –original draft, Writ- ing–review & editing. Rashed Alremeithi: Writing –original draft, Writing –review & editing. Ali Pourmand: Conceptualization, Supervi- sion, Writing –original draft, Writing –review & editing.
Evaluation of surface wear in rotary and reciprocating nickel-titanium instruments after use in curved root canals	What is the age of studied population ?	"The age of the studied population is not explicitly mentioned in the context."	41,131	182,922	INTRODUCTION ................................ ................................ ................................ .................. 1 1.1. History and development of endodontic instruments ................................ .................. 2 1.1.1. Firstgeneration endodontic instruments ................................ .............................. 3 1.1.2. Secondgeneration endodontic instruments ................................ ......................... 4 1.1.3. Thirdgeneration endodontic instruments ................................ ............................ 5 1.1.4. Fourthgeneration endodontic instruments ................................ ........................... 6 1.1.5. Fifthgeneration endodontic instruments ................................ ............................. 7 1.2. Mechanical properties of the nickel titanium alloy ................................ ..................... 7 1.1.6. Martensitic transformation ................................ ................................ ................... 9 1.1.7. Superelasticity ................................ ................................ ................................ ... 10 1.1.8. Shape memory ................................ ................................ ................................ .... 10 1.1.9. Advantages of using NiTi engine driven instruments ................................ ........ 11 1.3. Thermomechanical treatment of the Ni Ti alloy ................................ ....................... 11 1.4. Rotary instrumentation systems ................................ ................................ ................. 13 1.4.1. Rotational movement ................................ ................................ .............................. 13 1.4.2. Xpendo Shaper ................................ ................................ ................................ ...... 14 1.4.3. TruNatomy ................................ ................................ ................................ .............. 15 1.5. Reciprocating instrumentation systems ................................ ................................ ............. 16 1.5.1. Reciprocating movement ................................ ................................ ........................ 16 1.5.2. Reciproc Blue ................................ ................................ ................................ .......... 17 1.5.3. WaveOne Gold ................................ ................................ ................................ ........ 18 1.6. Failure of endodontic instruments ................................ ................................ ................. 19 1.6.1. Cyclic fatigue (CF) ................................ ................................ ................................ . 19 1.6.2. Torsional fatigue (TF) ................................ ................................ ............................. 21 1.7. The surface wear of NiTi instruments ................................ ................................ ........... 23 1.7.1. Scanning electron microscopy ................................ ................................ ................ 23 1.7.2. Atomic force microscopy ................................ ................................ ........................ 25 1.7.3. Optical profilometry ................................ ................................ ................................ 28 1.7.3.1. Advantages and disadvantages of optical profilometry ................................ ....... 28 2. AIMS AND OBJECTIVES ................................ ................................ ................................ .. 30 3. MATERIALS AND METHODS ................................ ................................ ......................... 33 3.1. Sample selection ................................ ................................ ................................ ............ 34 3.2. Root canals selection ................................ ................................ ................................ ..... 34 3.3. Root canal instrumentation ................................ ................................ ............................ 37 3.4. Threedimensional optical profilometry analysis ................................ .......................... 45 3.5. Cyclic fatigue test ................................ ................................ ................................ .......... 48 3.6. Statistical analysis ................................ ................................ ................................ .......... 48 4. RESULTS ................................ ................................ ................................ ............................. 49 5. DISCUSSION ................................ ................................ ................................ ...................... 59 6. CONCLUSIONS ................................ ................................ ................................ .................. 67 7.

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