Sugammadex: NOT your silver bullet! Why monitoring still matters

2024 marks a pivotal year in the history of neuromuscular block (NMB) management. Several significant developments stand out.  First, there is now a global evidence-based consensus for monitoring practice, with guidance from numerous anaesthesia organizations including the UK’s Association of Anaesthetists (1) and culminating in publication of the recent ASA and ESAIC guidelines (2),(3).  Second, the patent expiry for sugammadex in Europe will result in reduced prices and will increase availability and use.

Sugammadex offers a significant advantage over neostigmine due to its ability to speedily reverse NMB regardless of depth.  By contrast neostigmine has a ceiling effect and requires high levels of spontaneous recovery before reliable antagonism. (2)(3)

 It also carries risks of serious albeit rare events such as anaphylaxis and cardiovascular events (4), as well as hormonal capture including implications for women and contraceptive use.   

The true incidence of anaphylaxis with sugammadex is not entirely clear but has been listed as 1:2500 in a single centre retrospective study (5). A recent study by Takazawa revealed an incidence of 1:5000 (6).

Despite its advantages, sugammadex is not a “silver bullet” for reversing NMB. Residual paralysis can still occur in up to 10% of patients when relying solely on sugammadex reversal without quantitative neuromuscular monitoring. (7)(8)

Bowdle neatly demonstrated the variability of response with sugammadex, and the wide range of dose requirement and response (9).  While 87% of cardiac surgical patients needed less than the manufacturer-recommended dose of sugammadex to achieve Train-of-Four ratio (TOFr) > 0.9, 13% required more. This underscores the need to accurately determine the correct reversal dose (based on block level prior to reversal) and measure the response using quantitative TOF monitoring, to guarantee muscle function recovery. 

Reports of residual paralysis or “re-curarization” despite reversal with sugammadex underscore the importance of monitoring, especially in high-risk patients such as the very young, the elderly, those receiving additional drugs like magnesium and aminoglycoside antibiotics and when large doses of rocuronium are given. (10) 

The assumption that monitoring is unnecessary if sugammadex is used, is flawed.  Effective monitoring eliminates guesswork, ensuring precision in drug delivery, patient outcome and safety. The UK’s National Audit Project (NAP5) highlights that accidental awareness under anaesthesia primarily occurs when NMB drugs are used and advocates judicious use of NMB drugs, only when needed and in the smallest doses and using quantitative NMB monitoring to ensure TOFr > 0.9 before awakening and extubation (11). 

Failure to monitor NMB leaves anaesthetists guessing whether patients have adequate recovery of muscle function or not. Such guesswork is surely unacceptable as would be guessing blood pressure reading before and after giving a vasopressor. It befits clinicians to target drug delivery with precision and based on individualised patient requirements, rather than as a one size fits all. 

In so doing, the eye-opening benefit to clinicians allows for enhanced patient safety by facilitating NMB practice and the elimination of residual paralysis.
 

In conclusion, sugammadex can undoubtedly enhance overall NMB management, but it should be used as part of a comprehensive strategy underpinned by quantitative neuromuscular monitoring. (12)

This should include preoperative planning, consideration of patient risk factors, surgical requirements, patient positioning for monitor access and effective quantitative monitoring.  Such an approach will ensure optimal patient outcomes.  In doing so, the goal of elimination of residual paralysis is achievable.

1. Klein AA, Meek T, Allcock E, et al. Recommendations for standards of monitoring during anaesthesia and recovery 2021: guideline from the Association of Anaesthetists. Anaesthesia 2021; 76: 1212–23
2. Thilen SR, Weigel WA, Todd MM, et al. 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: a report by the American Society of Anesthesiologists Task Force on Neuromuscular Blockade. Anesthesiology 2023; 138: 13–41. 
3. Fuchs-Buder T, Romero CS, Lewald H, et al. Peri-operative management of neuromuscular blockade: a guideline from the European Society of Anaesthesiology and Intensive Care. European Journal of Anaesthesiology 2023; 40: 82–94. 
4. Savic L, Savic S, Hopkins PM. Anaphylaxis to sugammadex: should we be concerned by the Japanese experience? British Journal of Anaesthesia 2020; 124: 370–2. 
5. Miyazaki Y, Sunaga H, Kida K, Hobo S.  Incidence of anaphylaxis associated with Sugammadex.  Anesth Analg 2018; 126: 1505-8
6. Takazawa T, Horiuchi T, Nagumo K et al.  The Japanese epidemiologic study for perioperative anaphylaxis, a prospective nationwide study:  allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.  British Journal of Anaesthesia 2023; 131: 159-69  
7. Kotake Y, Ochiai R, Suzuki T and colleagues.  Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg 2013; 117: 345-51.
8. Togioka BM, Yanez D, Aziz MF, Higgins JR, Tekkali P, Treggiari MM. Randomised controlled trial of sugammadex or neostigmine for reversal of neuromuscular block on the incidence of pulmonary complications in older adults undergoing prolonged surgery. Br J Anaesth 2020; 124: 553-61.
9. Bowdle TA, Haththotuwegama KJ, Jelacic S, Nguyen ST, Togashi K, Michaelsen KE. A dose-finding study of sugammadex for reversal of rocuronium in cardiac surgery patients and postoperative monitoring for recurrent paralysis. Anesthesiology 2023; 139: 6–15.
10. Hunter JM, Blobner M.  Under dosing and overdosing of neuromuscular blocking drugs and reversal agents: beware of the risks.  British Journal of Anaesthesia 2024; 132: 461-5
11. Pandit JJ, Andrade J, Bogod DG and colleagues; Royal College of Anaesthetists; Association of Anaesthetists of Great Britain and Ireland. 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors. Br J Anaesth 2014; 113: 549-59.
12. Rodney G, Raju PKBC, Brull SJ.  Residual neuromuscular block: time to consign it to history.  Anaesthesia 2024; 79: 344-8