- Email: [email protected]
Hidden universality of residual neuromuscular block
Correspondence
2.
3.
4.
5.
6.
7.
8.
Declaration of interest None declared. 9.
References 1. Brueckmann B, Sasaki N, Grobara P, et al. Effects of sugammadex on incidence of postoperative residual neuromuscular
blockade: a randomized, controlled study. Br J Anaesth 2015; 115: 743–51 Fortier LP, McKeen D, Turner K, et al. The RECITE Study: a Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade. Anesth Analg 2015; 121: 366–72 Murphy GS, Szokol JW, Avram MJ, et al. Intraoperative acceleromyography monitoring reduces symptoms of muscle weakness and improves quality of recovery in the early postoperative period. Anesthesiology 2011; 115: 946–54 Todd MM, Hindman BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department: follow-up observations. Anesth Analg 2015; 121: 836–8 Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department. Anesth Analg 2014; 119: 323–31 Kotake Y, Ochiai R, Suzuki T, et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg 2013; 117: 345–51 Sasaki N, Meyer MJ, Malviya SA, et al. Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes. A prospective study. Anesthesiology 2014; 121: 959–68 Rahe-Meyer N, Fennema H, Schulman S, et al. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients. Anesthesiology 2014; 121: 969–77 Tassonyi E, Pongrácz A, Nemes R, Asztalos L, Lengyel S, Fülesdi B. Reversal of pipecuronium-induced moderate neuromuscular block with sugammadex in the presence of a sevoflurane anesthetic: A randomized trial. Anesth Analg 2015; 121: 373–80 doi:10.1093/bja/aew006
Hidden universality of residual neuromuscular block M. Eikermann* Boston, MA, USA *E-mail: [email protected]
Editor—The American virologist Dr J. R. Paul1 introduced the term ‘the hidden universality of infection’ to describe that clinically apparent infections typically are far outnumbered by those patients in whom the meaningful infection produces no sign or symptom of disease. In his letter to the Editor, Michael M. Todd, an American anaesthetist of Iowa University with an interest in clinical implementation science, emphasizes the hidden universality of residual neuromuscular block, posing the question as to whether or not its high occurrence is still an acceptable normal practice. This response to Dr Todd’s letter provides additional information and reflection on the hidden universality of residual neuromuscular block, also in light of our own work recently published in the BJA and Anesthesiology, and referenced to by Dr Todd.2 3 The hidden universality of residual neuromuscular block was initially brought to the attention of anaesthetists in 1979 by
Jorgen Viby-Mogensen and colleagues,4 who reported on a 42% incidence of unidentified residual neuromuscular block in the recovery room. More than 35 yr later, studies published in reputable journals2 3 5 6 tell us that the incidence of residual block did not change, despite the availability of new drugs and new protocols that should help us to prevent the ‘epidemic disease’. Of note, the incidence of residual neuromuscular paralysis depends on the type of surgery; residual paralysis is consistently high after major abdominal surgery when repetitive doses of neuromuscular blocking agent are given,2 and occurs less frequently (in ∼20% of postoperative patients) in mixed surgical cohorts.3 Another predictor of residual paralysis is age, as been recently reported by Glenn Murphy and colleagues.6 We know that residual neuromuscular block is a relevant problem because it leads to an important increase in respiratory morbidity and health-care utilization.5 7 8 Fortunately,
Downloaded from http://bja.oxfordjournals.org/ at Flinders University of South Australia on February 14, 2016
based criteria for antagonism with sugammadex, but not with neostigmine. The authors also note that providers were given specific instructions in the use of sugammadex, but no comparable protocol was in place for the use of neostigmine (and it should be noted that there was much more variability in neostigmine dosing as compared with sugammadex). This lack of blinding, from the start of the procedure, combined with a more controlled protocol in only one of the two groups (the sugammadex group), is a potential source of bias. There have been previous double-blinded trials with sugammadex.8 9 At the very least, delaying the moment of randomization until immediately before antagonism (instead of before the start of the procedure) would have been preferable. Although data are unclear, our experience suggests that achieving a 0% incidence of residual paralysis with neostigmine (even with quantitative monitoring) is probably not possible, at least not without extremely prolonged waiting periods or better monitoring. At the present time, only sugammadex offers this possibility, and then, ideally, when monitoring is used. However, I suspect that the incidence of residual paralysis with neostigmine would be much lower than reported if the investigators had used different rocuronium and neostigmine dosing practices, had used (and attended to) quantitative block monitoring, made some effort to blind the providers, and established equivalent management protocols in both groups.
| 435
436
| Correspondence
for the use of neuromuscular blocking agents and persistently to implement best practices into clinical medicine.13
Declaration of interest M.E. has received research funding from MERCK and holds equity shares at Calabash Biotechnology Inc.
References 1. Paul JR. A History of Poliomyelitis. New Haven: Yale University Press 2. Brueckmann B, Sasaki N, Grobara P, et al. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study. Br J Anaesth 2015; 115: 743–51 3. Sasaki N, Meyer MJ, Malviya SA, et al. Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes: a prospective study. Anesthesiology 2014; 121: 959–68 4. Viby-Mogensen J, Jørgensen BC, Ørding H. Residual curarization in the recovery room. Anesthesiology 1979; 50: 539–41 5. Martinez-Ubieto J, Ortega-Lucea S, Pascual-Bellosta A, et al. Prospective study of residual neuromuscular block and postoperative respiratory complications in patients reverted with neostigmine versus sugammadex. Minerva Anestesiol Advance Access published on October 16, 2015 6. Murphy GS, Szokol JW, Avram MJ, et al. Residual neuromuscular block in the elderly: incidence and clinical implications. Anesthesiology 2015; 123: 1322–36 7. McLean DJ, Diaz-Gil D, Farhan HN, Ladha KS, Kurth T, Eikermann M, et al. Dose-dependent association between intermediate-acting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology 2015; 122: 1201–13 8. Staehr-Rye AK, Grabitz SD, Thevathasan T, et al. Effects of residual paralysis on postoperative pulmonary function and hospital length of stay. ASA Abstract 2015; A3038 9. Murphy GS, Szokol JW, Marymont JH, et al. Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit. Anesthesiology 2008; 109: 389–98 10. Videira RL, Vieira JE. What rules of thumb do clinicians use to decide whether to antagonize nondepolarizing neuromuscular blocking drugs? Anesth Analg 2011; 113: 1192–6 11. Kotake Y, Ochiai R, Suzuki T, et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg 2013; 117: 345–51 12. Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department. Anesth Analg 2014; 119: 323–31 13. Brull SJ, Prielipp RC. Reversal of neuromuscular blockade: “identification friend or foe”. Anesthesiology 2015; 122: 1183–5 doi:10.1093/bja/aew007
Downloaded from http://bja.oxfordjournals.org/ at Flinders University of South Australia on February 14, 2016
similar to well-known infectious diseases, there are promising strategies available to eradicate residual block by prevention: judicious use of neuromuscular blocking agent, quantitative neuromuscular monitoring, and titration of antagonistic agents to effect.9 How then do we best explain that anaesthetists around the world are unable to eliminate the hidden universality of residual neuromuscular block? Anaesthetists often apply an interesting framework of rules of thumb that is not always informed by best practices. Our heuristics10 for adequate recovery are typically based on assessment of breathing pattern (measured, for instance, by visual assessment of volume oscillations of the reservoir bag); those are erroneously interpreted as sufficient signs of neuromuscular recovery, instead of requesting documentation of objective indicators of recovery of upper airway muscles [trainof-four (TOF) ratio=0.9]. In our clinic (in accordance with the observation of others), even the availability of quantitative neuromuscular transmission monitors did not translate to proper use of the equipment. Many colleagues use our sophisticated quantitative TOF-Watch SX monitors merely as simple peripheral nerve stimulators to document the TOF count, probably in an attempt to save time and money. The available transducers are not cheap, need to be calibrated before injection of a neuromuscular blocking agent, and are short lived. The absence of consistent use of objective monitoring of neuromuscular transmission and cognitive errors related to the effectiveness of neostigmine may explain the observed persistence in the hidden universality of residual neuromuscular block.2 3 5 6 What can anaesthetists learn from infectious disease doctors? Successful treatment of disease requires close clinical and epidemiological observations, and we are about to take this step successfully now by designing proper effectiveness trials. A missing piece we addressed recently with our assessor-blinded clinical effectiveness study2 was to evaluate how a new treatment (antagonism by encapsulation) when properly implemented can decrease the occurrence of residual paralysis observed under standard-of-care conditions in a busy operating room. For that reason, in our study,2 use of TOF monitoring was not mandatory during surgery, and the mode of objective monitoring (qualitative or quantitative) was also left to the discretion of the anaesthetist. As outlined in the Discussion in our published manuscript,2 we do not conclude that absence of residual neuromuscular block in our present study observed with the new treatment reflects significance of absence; residual neuromuscular block occurred in ∼5% of patients after sugammadex administration without TOF monitoring.11 Overall, we applaud Dr Todd for developing an interest to support the goal of eliminating residual neuromuscular block.12 Infectious disease doctors reached out to other colleagues to eliminate epidemic diseases. Important next steps for us to take on our way to eradicate postoperative residual paralysis should include synergistic, interdisciplinary efforts of stakeholders in perioperative medicine to develop specific guidelines
2.
3.
4.
5.
6.
7.
8.
Declaration of interest None declared. 9.
References 1. Brueckmann B, Sasaki N, Grobara P, et al. Effects of sugammadex on incidence of postoperative residual neuromuscular
blockade: a randomized, controlled study. Br J Anaesth 2015; 115: 743–51 Fortier LP, McKeen D, Turner K, et al. The RECITE Study: a Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade. Anesth Analg 2015; 121: 366–72 Murphy GS, Szokol JW, Avram MJ, et al. Intraoperative acceleromyography monitoring reduces symptoms of muscle weakness and improves quality of recovery in the early postoperative period. Anesthesiology 2011; 115: 946–54 Todd MM, Hindman BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department: follow-up observations. Anesth Analg 2015; 121: 836–8 Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department. Anesth Analg 2014; 119: 323–31 Kotake Y, Ochiai R, Suzuki T, et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg 2013; 117: 345–51 Sasaki N, Meyer MJ, Malviya SA, et al. Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes. A prospective study. Anesthesiology 2014; 121: 959–68 Rahe-Meyer N, Fennema H, Schulman S, et al. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients. Anesthesiology 2014; 121: 969–77 Tassonyi E, Pongrácz A, Nemes R, Asztalos L, Lengyel S, Fülesdi B. Reversal of pipecuronium-induced moderate neuromuscular block with sugammadex in the presence of a sevoflurane anesthetic: A randomized trial. Anesth Analg 2015; 121: 373–80 doi:10.1093/bja/aew006
Hidden universality of residual neuromuscular block M. Eikermann* Boston, MA, USA *E-mail: [email protected]
Editor—The American virologist Dr J. R. Paul1 introduced the term ‘the hidden universality of infection’ to describe that clinically apparent infections typically are far outnumbered by those patients in whom the meaningful infection produces no sign or symptom of disease. In his letter to the Editor, Michael M. Todd, an American anaesthetist of Iowa University with an interest in clinical implementation science, emphasizes the hidden universality of residual neuromuscular block, posing the question as to whether or not its high occurrence is still an acceptable normal practice. This response to Dr Todd’s letter provides additional information and reflection on the hidden universality of residual neuromuscular block, also in light of our own work recently published in the BJA and Anesthesiology, and referenced to by Dr Todd.2 3 The hidden universality of residual neuromuscular block was initially brought to the attention of anaesthetists in 1979 by
Jorgen Viby-Mogensen and colleagues,4 who reported on a 42% incidence of unidentified residual neuromuscular block in the recovery room. More than 35 yr later, studies published in reputable journals2 3 5 6 tell us that the incidence of residual block did not change, despite the availability of new drugs and new protocols that should help us to prevent the ‘epidemic disease’. Of note, the incidence of residual neuromuscular paralysis depends on the type of surgery; residual paralysis is consistently high after major abdominal surgery when repetitive doses of neuromuscular blocking agent are given,2 and occurs less frequently (in ∼20% of postoperative patients) in mixed surgical cohorts.3 Another predictor of residual paralysis is age, as been recently reported by Glenn Murphy and colleagues.6 We know that residual neuromuscular block is a relevant problem because it leads to an important increase in respiratory morbidity and health-care utilization.5 7 8 Fortunately,
Downloaded from http://bja.oxfordjournals.org/ at Flinders University of South Australia on February 14, 2016
based criteria for antagonism with sugammadex, but not with neostigmine. The authors also note that providers were given specific instructions in the use of sugammadex, but no comparable protocol was in place for the use of neostigmine (and it should be noted that there was much more variability in neostigmine dosing as compared with sugammadex). This lack of blinding, from the start of the procedure, combined with a more controlled protocol in only one of the two groups (the sugammadex group), is a potential source of bias. There have been previous double-blinded trials with sugammadex.8 9 At the very least, delaying the moment of randomization until immediately before antagonism (instead of before the start of the procedure) would have been preferable. Although data are unclear, our experience suggests that achieving a 0% incidence of residual paralysis with neostigmine (even with quantitative monitoring) is probably not possible, at least not without extremely prolonged waiting periods or better monitoring. At the present time, only sugammadex offers this possibility, and then, ideally, when monitoring is used. However, I suspect that the incidence of residual paralysis with neostigmine would be much lower than reported if the investigators had used different rocuronium and neostigmine dosing practices, had used (and attended to) quantitative block monitoring, made some effort to blind the providers, and established equivalent management protocols in both groups.
| 435
436
| Correspondence
for the use of neuromuscular blocking agents and persistently to implement best practices into clinical medicine.13
Declaration of interest M.E. has received research funding from MERCK and holds equity shares at Calabash Biotechnology Inc.
References 1. Paul JR. A History of Poliomyelitis. New Haven: Yale University Press 2. Brueckmann B, Sasaki N, Grobara P, et al. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study. Br J Anaesth 2015; 115: 743–51 3. Sasaki N, Meyer MJ, Malviya SA, et al. Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes: a prospective study. Anesthesiology 2014; 121: 959–68 4. Viby-Mogensen J, Jørgensen BC, Ørding H. Residual curarization in the recovery room. Anesthesiology 1979; 50: 539–41 5. Martinez-Ubieto J, Ortega-Lucea S, Pascual-Bellosta A, et al. Prospective study of residual neuromuscular block and postoperative respiratory complications in patients reverted with neostigmine versus sugammadex. Minerva Anestesiol Advance Access published on October 16, 2015 6. Murphy GS, Szokol JW, Avram MJ, et al. Residual neuromuscular block in the elderly: incidence and clinical implications. Anesthesiology 2015; 123: 1322–36 7. McLean DJ, Diaz-Gil D, Farhan HN, Ladha KS, Kurth T, Eikermann M, et al. Dose-dependent association between intermediate-acting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology 2015; 122: 1201–13 8. Staehr-Rye AK, Grabitz SD, Thevathasan T, et al. Effects of residual paralysis on postoperative pulmonary function and hospital length of stay. ASA Abstract 2015; A3038 9. Murphy GS, Szokol JW, Marymont JH, et al. Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit. Anesthesiology 2008; 109: 389–98 10. Videira RL, Vieira JE. What rules of thumb do clinicians use to decide whether to antagonize nondepolarizing neuromuscular blocking drugs? Anesth Analg 2011; 113: 1192–6 11. Kotake Y, Ochiai R, Suzuki T, et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg 2013; 117: 345–51 12. Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department. Anesth Analg 2014; 119: 323–31 13. Brull SJ, Prielipp RC. Reversal of neuromuscular blockade: “identification friend or foe”. Anesthesiology 2015; 122: 1183–5 doi:10.1093/bja/aew007
Downloaded from http://bja.oxfordjournals.org/ at Flinders University of South Australia on February 14, 2016
similar to well-known infectious diseases, there are promising strategies available to eradicate residual block by prevention: judicious use of neuromuscular blocking agent, quantitative neuromuscular monitoring, and titration of antagonistic agents to effect.9 How then do we best explain that anaesthetists around the world are unable to eliminate the hidden universality of residual neuromuscular block? Anaesthetists often apply an interesting framework of rules of thumb that is not always informed by best practices. Our heuristics10 for adequate recovery are typically based on assessment of breathing pattern (measured, for instance, by visual assessment of volume oscillations of the reservoir bag); those are erroneously interpreted as sufficient signs of neuromuscular recovery, instead of requesting documentation of objective indicators of recovery of upper airway muscles [trainof-four (TOF) ratio=0.9]. In our clinic (in accordance with the observation of others), even the availability of quantitative neuromuscular transmission monitors did not translate to proper use of the equipment. Many colleagues use our sophisticated quantitative TOF-Watch SX monitors merely as simple peripheral nerve stimulators to document the TOF count, probably in an attempt to save time and money. The available transducers are not cheap, need to be calibrated before injection of a neuromuscular blocking agent, and are short lived. The absence of consistent use of objective monitoring of neuromuscular transmission and cognitive errors related to the effectiveness of neostigmine may explain the observed persistence in the hidden universality of residual neuromuscular block.2 3 5 6 What can anaesthetists learn from infectious disease doctors? Successful treatment of disease requires close clinical and epidemiological observations, and we are about to take this step successfully now by designing proper effectiveness trials. A missing piece we addressed recently with our assessor-blinded clinical effectiveness study2 was to evaluate how a new treatment (antagonism by encapsulation) when properly implemented can decrease the occurrence of residual paralysis observed under standard-of-care conditions in a busy operating room. For that reason, in our study,2 use of TOF monitoring was not mandatory during surgery, and the mode of objective monitoring (qualitative or quantitative) was also left to the discretion of the anaesthetist. As outlined in the Discussion in our published manuscript,2 we do not conclude that absence of residual neuromuscular block in our present study observed with the new treatment reflects significance of absence; residual neuromuscular block occurred in ∼5% of patients after sugammadex administration without TOF monitoring.11 Overall, we applaud Dr Todd for developing an interest to support the goal of eliminating residual neuromuscular block.12 Infectious disease doctors reached out to other colleagues to eliminate epidemic diseases. Important next steps for us to take on our way to eradicate postoperative residual paralysis should include synergistic, interdisciplinary efforts of stakeholders in perioperative medicine to develop specific guidelines