Correspondence  |   July 2017
Should Neuromuscular Blocking Agents Always Be Reversed?
Author Notes
  • Massachusetts General Hospital, Boston, Massachusetts (M.J.M.).
  • (Accepted for publication April 13, 2017.)
    (Accepted for publication April 13, 2017.)×
Article Information
Correspondence   |   July 2017
Should Neuromuscular Blocking Agents Always Be Reversed?
Anesthesiology 7 2017, Vol.127, 194. doi:
Anesthesiology 7 2017, Vol.127, 194. doi:
To the Editor:
We read with great interest the Bulka et al.1  article associating intraoperative neuromuscular blockade administration with postoperative pneumonia. We found the conclusion that not “reversing” neuromuscular blockade was associated with an increased risk of postoperative pneumonia to be particularly important. However, we find the title of the accompanying editorial (“To Reverse or Not to Reverse?” The Answer Is Clear!2 ) to be misleading, and the second part of the text in the editorial’s figure (“reversal of neuromuscular blocking agents should be routine”) to differ from what we would consider safe and patient-centered practice.
We believe that reversal of neuromuscular blockade should only occur when guided by neuromuscular transmission monitoring, preferably quantitative. The authors also believe this, as it is written in their editorial: “Unless there is quantitative evidence that the TOF [train-of-four] ratio at the adductor pollicis has returned to a value of more than or equal to 0.9, an appropriate dose of an anticholinesterase agent or sugammedex should be administered at the end of surgery.”2 However, we find this statement to be incongruent with their conclusion that “reversal of neuromuscular blocking agents should be routine.”
“Routine reversal” of neuromuscular blockade with neostigmine is not settled science. It has been shown to improve clinical outcomes,1,3  have little effect on clinical outcome,4,5  and even cause harm at high doses,6  all dependent upon clinical context. Neostigmine should not be used in a patient with deep neuromuscular blockade.7  Patients who have already recovered their strength (TOF greater than 0.9) may be weakened through the administration of neostigmine, as demonstrated in a healthy volunteer study.8  The only way to prevent these two dangerous situations is to monitor the patient depth of neuromuscular blockade and reverse appropriately.9 
Furthermore, we would like to clarify an additional point from the editorial regarding our prospective, observational study of 3,000 postoperative patients who were intraoperatively administered intermediate-acting neuromuscular blocking agents.10  Quantitative neuromuscular transmission monitoring within 10 min of postanesthesia care unit arrival was included in the statistical model. In our study, neostigmine usage was associated with increased diagnoses of atelectasis, and, in post hoc analysis, unwarranted neostigmine usage was independently associated with pulmonary edema and reintubation.
We offer the strong suggestion that the administration of neuromuscular blocking agents and reversal agents be guided by frequent neuromuscular transmission monitoring, preferably quantitatively. No reversal should be administered until there are at least two twitches, and no reversal should be administered if there is a TOF greater than 0.9.11 
Competing Interests
Dr. Eikermann received research funding from Merck & Co. (Kenilworth, New Jersey) and holds equity stakes in Calabash Bioscience, Inc. (College Park, Maryland). The other author declares no competing interests.
Matthew J. Meyer, M.D., Matthias Eikermann, M.D., Ph.D. Massachusetts General Hospital, Boston, Massachusetts (M.J.M.).
Bulka, CM, Terekhov, MA, Martin, BJ, Dmochowski, RR, Hayes, RM, Ehrenfeld, JM Nondepolarizing neuromuscular blocking agents, reversal, and risk of postoperative pneumonia. Anesthesiology 2016; 125:647–55 [Article] [PubMed]
Murphy, GS, Kopman, AF “To reverse or not to reverse?”: The answer is clear! Anesthesiology 2016; 125:611–4 [Article] [PubMed]
Bronsert, MR, Henderson, WG, Monk, TG, Richman, JS, Nguyen, JD, Sum-Ping, JT, Mangione, MP, Higley, B, Hammermeister, KE Intermediate-acting nondepolarizing neuromuscular blocking agents and risk of postoperative 30-day morbidity and mortality, and long-term survival. Anesth Analg 2017; 124:1476–83 [Article] [PubMed]
Meyer, MJ, Bateman, BT, Kurth, T, Eikermann, M Neostigmine reversal doesn’t improve postoperative respiratory safety. BMJ 2013; 346:f1460 [Article] [PubMed]
Thevathasan, T, Shih, S, Safavi, KC, Berger, DL, Burns, SM, Que, AM, Grabitz, SD, Glidden, RS, Zafonte, RD, Eikermann, M, Schneider, JC Dose-dependent association between intraoperative non-depolarising neuromuscular blocking agent dose and 30-day readmission following abdominal surgery. Br J Anaesth 2017; (in-press)
McLean, DJ, Diaz-Gil, D, Farhan, HN, Ladha, KS, Kurth, T, Eikermann, M Dose-dependent association between intermediate-acting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology 2015; 122:1201–13 [Article] [PubMed]
Brull, SJ, Murphy, GS Residual neuromuscular block: Lessons unlearned–Part II: methods to reduce the risk of residual weakness. Anesth Analg 2010; 111:129–40 [Article] [PubMed]
Herbstreit, F, Zigrahn, D, Ochterbeck, C, Peters, J, Eikermann, M Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure. Anesthesiology 2010; 113:1280–8 [Article] [PubMed]
Kopman, AF, Eikermann, M Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia 2009; 64(suppl 1):22–30 [Article] [PubMed]
Sasaki, N, Meyer, MJ, Malviya, SA, Stanislaus, AB, MacDonald, T, Doran, ME, Igumenshcheva, A, Hoang, AH, Eikermann, M Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes: A prospective study. Anesthesiology 2014; 121:959–68 [Article] [PubMed]
Van Pelt, M, Chitilian, HV, Eikermann, MMulti-faceted initiative designed to improve safety of neuromuscular blockade: Guide for authors: 51. Available at: Accessed August 26, 2016