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Monitoring and Pharmacologic Reversal of a Nondepolarizing Neuromuscular Blockade Should Be Routine

Miller, Ronald D., MD; Ward, Theresa A., BSN, RN

doi: 10.1213/ANE.0b013e3181e13522
Editorials: Editorials

From the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California.

Disclosure: The authors report no conflicts of interest.

Address correspondence and reprint requests to Ronald D. Miller, MD, Department of Anesthesia and Perioperative Care, University of California San Francisco, 521 Parnassus Ave., Box 0648, San Francisco, CA 94143. Address e-mail to

Accepted March 30, 2010

As evidenced by the presence of 2 review articles,1,2 1 survey,3 and 5 editorials in this issue, including this one,47Anesthesia & Analgesia has placed prime emphasis on the importance of residual neuromuscular blockade (NMB) following anesthesia and surgery. Why is this topic now generating so much attention when it has been known for decades? Quoting S.C. Cullen's comment made over 50 years ago,8 “It has been assumed that if a patient is capable of raising his head, moving an extremity or squeezing one's hand forcibly or is able to take a deep breath, there is no significant residual of a relaxant. Such is not the case … Muscle relaxants enjoy a remarkable reputation as a safe and useful preparation. They will continue in this capacity only if intelligently applied in their proper relationship to the anesthetic state by those who are alert to the early signs of deleterious effects associated with excessive and protracted relaxation.” These opinions reflected the state of knowledge in the late 1950s by S.C. Cullen, the then Chair of Anesthesia of the University of California, San Francisco.8 During that time, Churchill-Davidson and Christie9 “devised a method employing electrical stimuli” to monitor NMB. Despite Cullen's cautionary comments about a lingering NMB,8 he never mentions residual NMB in the Postoperative Care section of his book. In those days, they had long-acting and unpredictable neuromuscular blocking drugs (NMBDs) [i.e., d-tubocurarine and gallamine], in addition to succinylcholine and an acetylcholinesterase inhibitor, neostigmine. These drugs and others provided the basic principles for managing an NMB during anesthesia care in the future.

What are our conclusions 50 years later? The evidence is clear that residual NMB following the end of anesthesia currently and frequently occurs. This problem persists despite having NMBDs that are shorter-acting and more predictable regarding their duration of NMB than d-tubocurarine or gallamine. Although residual NMB probably existed following anesthesia 50 years ago, it was not widely viewed as a common problem. Perhaps the dependence on NMB for the anesthetic state was less and doses of NMBDs smaller. In fact, Cullen8 states: “It is good policy to adhere to the practice of using the muscle relaxant only to provide additional muscular relaxation needed after optimal concentrations of the anesthetic agent (or agents) used have been established.” Did this philosophy result in smaller doses of NMBDs being used in the past? If so, could smaller does of NMBDs account for no obvious residual NMB being present? We now have excellent neuromuscular monitoring capabilities and better NMBDs and yet residual NMB following anesthesia is surprisingly still a significant clinical problem.1,2 What are the reasons for this persistent problem? Despite persistent pleas from “experts” in clinical neuromuscular pharmacology the past 40 years and this issue of Anesthesia & Analgesia,17 neuromuscular monitoring is not widely used by anesthesiologists from both North America and Europe.3 Furthermore, neuromuscular monitoring is not considered as required standard monitoring in the United States. Clearly, the persistence of residual NMB after anesthesia suggests that monitoring should be routine. Before accepting this recommendation, we must ask whether the use of monitoring actually decreases the incidence of residual NMB. Furthermore, many patients apparently recover from a residual NMB without adverse effects. In fact, many anesthesiologists state that they have never seen a residual NMB.3 Even if those clinicians are correct with their observations, residual NMB is a well-documented adverse effect. When such an important adverse effect is possible, all safeguards should be used to ensure that this problem does not occur. We propose that routine neuromuscular monitoring and pharmacologic antagonism of NMB are 2 such “safeguards.” There seems to be no justified excuse to not routinely use neuromuscular monitors. Furthermore, neuromuscular monitors now display a numerical value for the response to peripheral nerve stimulation, which makes them even more useful to the clinician.4

Frustratingly, the common nonuse of neuromuscular monitoring must mean that our message has not been seriously considered by many anesthesiologists and/or is not effective. Clearly, the ineffectiveness of our message indicates that a revision is needed. Perhaps we the “experts” have used the wrong strategy. First, we need to acknowledge the limitations of neuromuscular monitoring. As indicated previously, Cullen8 knew that a normal head-lift for 5 seconds did not assure the absence of residual NMB. Yet the survey published in this issue of Anesthesia & Analgesia3 found that more than half of the respondents thought head-lift was a reliable indicator of recovery from NMB. In a way, Cullen8 and the respondents3 are both correct. If patients cannot lift their heads for 5 seconds, all would agree that they have residual NMB. On the other hand, if they can lift their heads for 5 seconds, it does not guarantee that the NMB has completely dissipated. This type of conclusion actually applies to all neuromuscular monitoring. If a residual NMB is detected by the monitor, the implications are clear. If a residual NMB is not evident, a neuromuscular block may still exist. Does that mean that such a monitor should not be used? The answer is that a monitor should be used. The overall conclusion is that there is no “magic bullet” and a combination of strategies needs to be utilized. Could routine monitoring of NMB and routine reversal of NMB with neostigmine or sugammadex eliminate residual NMB following anesthesia?

That a normal response to peripheral nerve stimulation does not guarantee absence of residual NMB was emphasized in the 1990s. For example, various muscle groups were still weak (e.g., pharyngeal muscles) even with a train-of-four (TOF) of >0.7, which led Eriksson et al.10 to recommend a new standard of >0.9 as an indicator of return of normal neuromuscular transmission. Conceptually, the issue is, how many receptors need to be free of NMBDs to ensure postanesthetic safety? That nicotinic receptors could be occupied with NMBDs and still have a normal response to peripheral nerve stimulation has been known for many years. Despite these limitations, routine neuromuscular monitoring should be used both intraoperatively and in the immediate postoperative period. Intraoperative monitoring has the potential to avoid unnecessarily large doses of NMBDs being given and facilitate the use of smaller total amounts of NMBDs. Reversal of NMB is more likely to be successful when antagonizing an NMB from smaller doses of NMBDs. Also, neuromuscular monitoring can provide strong, but not complete evidence that NMB has been adequately reversed.

Despite the recommendation to routinely use neuromuscular monitoring, the problem of residual NMB will not be completely solved. This conclusion has been predictable for a long time. In 1971, Waud and Waud11 provided conceptual information using a receptor occlusion technique. They found that even with a sustained response to tetanic stimuli of 50 Hz, >50%–70% of the receptors can still be occupied with NMBDs. The implication is that with some receptors still occupied with NMBDs, some muscle weakness could persist despite a neuromuscular monitor showing a normal (i.e., no residual paralysis) response. In addition to normal pharmacokinetic elimination of NMBD, routine reversal of NMB with neostigmine adds an additional margin of safety (i.e., additional receptors unoccupied with or free of NMBDs). Should reversal of NMB be routine? Would the combination of monitoring and pharmacologic reversal markedly decrease the incidence of residual NMB?

By using neuromuscular monitoring, persistence of NMB after surgery and anesthesia has been known for many years.12 However, the clinical importance of residual NMB became more evident in the last few years.1,2 Why is this so evident now? The relatively recent availability of large databases of patient outcomes exposed previously unrecognized complications, morbidity, and mortality in the postoperative period, which have been summarized in this issue of Anesthesia & Analgesia.1,2 Although these databases found adverse patient outcomes to be multifactorial, residual NMB and reversal (or lack of) issues were frequently a component of these clinical problems. In our opinion, these databases and our own review of many cases of adverse outcomes has led to the conclusion that reversal of NMB with neostigmine should be routine. Conversely, there should be written documentation as to why neostigmine was unnecessary. Administration of neostigmine will facilitate displacement of NMBDs from the nicotinic receptors. In the immediate postoperative period, logic seems to dictate that “when in doubt, we should have as many receptors as possible free of NMBDs.” It seems clear that when more receptors are free of NMBDs, the more likely that normal neuromuscular function will exist. Yet neostigmine is not free of problems. Neostigmine is well known to be complex, and atropine or glycopyrrolate is needed to counteract some of its muscarinic effects. Although some adverse effects can occur,13,14 reversal with neostigmine clearly facilitates recovery from a nondepolarizing NMB.15 Furthermore, using neuromuscular monitoring to “titrate” the amount of neostigmine to be given also seems questionable. At the risk of being repetitive, a TOF ratio >0.9 can still have 50% of the receptors occupied. To us, it seems that a “little” more neostigmine than that required to produce a TOF ratio of >0.9 should be given.

In conclusion, evidence and logic dictate that strong consideration be given to routine monitoring of NMB and pharmacologic antagonism (i.e., reversal) of a nondepolarizing NMB. This combination offers the anesthesiologist the best opportunity to attenuate the occurrence, but probably not eliminate residual NMB in the immediate postoperative period. The 3 excellent conclusions in the Viby-Mogensen and Claudius editorial6 include routine monitoring. We would add a fourth recommendation—routine administration of neostigmine or sugammadex (if available). We are envious of our colleagues in Europe where sugammadex is approved for clinical use. Although sugammadex is not approved for clinical use in the United States, it was our belief that appropriate doses of sugammadex might eliminate residual NMB as a clinical problem. Time will tell.

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