His previous publications about bacterial filters can be found here and here (illustrated below).

We have a longstanding shared interest with Alan in anesthesia patient safety and prevention of anesthetic drug administration errors in particular. Previous publications that we co-authored can be found here and here.

Some of our previous publications concerning infection prevention in anesthesia practice can be found here, here and here.

Alan has had a distinguished career as reflected in this brief bio—

Alan Merry is Professor Emeritus at the University of Auckland and Honorary Consultant in the Department of Cardiothoracic and Otorhinolaryngology Anaesthesia at Auckland City Hospital. His previous roles include Head of the School of Medicine and then Deputy Dean of the Faculty of Medical and Health Sciences, University of Auckland. He was Chair of the Board of the New Zealand Health Quality and Safety Commission and a foundation Board member of Lifebox, an international charity which aims to improve standards of anaesthesia and surgical care in low-income areas of the world. His books, book chapters and papers in peer-reviewed journals reflect interests in patient safety, quality improvement in healthcare, global health and simulation. He is an Officer of the New Zealand Order of Merit and a Fellow of the Royal Society of New Zealand.

noun

1. An infallible means of attack or defense.

2. A simple remedy for a difficult or intractable problem.

3. A bullet made of silver, usually with reference to the folkloric belief that such bullets are the only weapons which can kill a werewolf.

I am joined in this post by Dr. Michael Todd. Dr. Todd is a neuroanesthesiologist and Vice Chair for Research at the University of Minnesota Department of Anesthesiology. Dr. Todd is a former Chair of the Department of Anesthesiology at the University of Iowa and is a former Editor-in-Chief of Anesthesiology. Dr. Todd is a coauthor of the 2023 American Societyof Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade.

Mike and I recorded a discussion about sugammadex which you can view above. In addition, you can read the text posted below, which includes hotlinks to references that we mention in the video.

My group published an article in Anesthesiology in 2023 in which we determined the dose-response for sugammadex using 50 mg increments of sugammadex. It turned out that most patients required less than either the 2 or 4mg/kg dose (depending upon the twitch response at the time of reversal), but some of the patients required more than the recommended dose of sugammadex. We also found that 2 of the 97 patients had RECURRENT (not residual) neuromuscular block—they achieved a train-of-four ratio of >0.9 but then slid back to <0.9 and required additional sugammadex. Mike Todd and Aaron Kopman wrote an editorial accompanying the article entitled “Sugammadex is Not a Silver Bullet”.

“Resistance” to Sugammadex

Indeed, we sometimes see two different kinds of failures of reversal with sugammadex. The first kind of failure we could call “resistance” to sugammadex. In this case, we give more, sometimes much more, than the recommended dose of sugammadex, but can’t get to a train-of-four ratio of at least 0.9 in a reasonable time. This phenomenon is not well documented and we don’t know how often it happens. But we know for sure that it happens. In a notable case report by Ortiz-Gomez et al, 9.7 mg/kg of sugammadex failed to produce reversal as judged by both acceleromyography and clinical signs of weakness. We too have seen some patients who we could not reverse with sugammadex; an example is shown in Figure 1. To the best of our knowledge there are no systematic studies of “resistance” to sugammadex that would tell us how often this happens.

Figure 1. Sugammadex 200 mg is administered when the post tetanic count is approximately 7. Another 200 mg is administered when the train-of-four ratio is approximately 0.75 (75%). Another 200 mg is administered when the train-of-four ratio is approximately 0.8. The recommended dose was 4 mg/kg or 320 mg, approximately half the dose that was actually used.

Another example is shown in Figure 2.

Figure 2. Reversal was started in the face of 1 twitch at 17:59. Incremental doses of sugammadex - reaching a total of 800mg (9mg/kg) were given over 30min before achieving full reversal. Note the exceptionally slow response to each dose of sugammadex. By contrast, the usual (and recommended) 4mg/kg dose of sugammadex would be "expected" to produce full reversal within a few minutes. The unmonitored administration of that recommended dose would have resulted in a substantial degree of residual paralysis.

We should note that this phenomenon is known to the manufacturer of sugammadex. For example, in the package insert is the statement: "Risk of Prolonged Neuromuscular Blockade: In clinical trials, a small number of patients experienced a delayed or minimal response to the administration of BRIDION."

Recurrent Neuromuscular Block Following Reversal with Sugammadex

Another kind of sugammadex failure is recurrent neuromuscular block. In this case, the train-of-four ratio is at least 0.9 following sugammadex administration, but afterwards, at a time that can vary considerably, the train-of-four ratio declines and is less than 0.9. Although the incidence of this problem is unknown, recurrent neuromuscular blockade has been noted in a large number of studies. We have briefly reviewed the results of some of these studies in the supplement to an article. Of note, vecuronium is not as tightly bound to sugammadex as rocuronium, and reversal of vecuronium with sugammadex may be more vulnerable to recurrent neuromuscular block.

What is the mechanism?

We don’t know the mechanism of resistance to sugammadex or recurrent neuromuscular block. Some have theorized that recurrent neuromuscular block is due to redistribution of neuromuscular blocking drug from peripheral pharmacokinetic compartments into the central compartment at a time when there is inadequate unbound sugammadex to encapsulate the neuromuscular blocking drug. Although plausible, to the best of our knowledge there is no actual evidence for this idea.

What should we do?

What should we do about these failures of sugammadex? The incidence of these events is uncertain but occur frequently enough for us to be concerned. First, it is imperative to monitor reversal with quantitative twitch monitoring. The approach of simply giving a big dose of sugammadex and hoping for the best is not a good way to go. Second, we believe it is wise to use rocuronium and other neuromuscular blocking drugs in as small a dose as possible, consistent with achieving whatever the desired effect is in a given situation. We should not assume that sugammadex is a silver bullet that can always reverse any dose of a neuromuscular blocking drug.