CON: Suddenly Sugammadex: Should Sugammadex Become the New ICU Standard for Reversal

by Gozde Demiralp, MD
Assistant Professor Medical Director, Preoperative Assessment Unit (PAU), Division of Critical Care Medicine Department of Anesthesiology, College of Medicine, University of Oklahoma Health Sciences Center Oklahoma City, OK

Volume 28 | Issue 2 | Summer 2017

Sugammadex, a new steroidal muscle relaxant encapsulator, is now officially in the US and Canadian market and is quickly gaining popularity as the best reversal agent for any depth of neuromuscular blockade (NMB) that is provided by rocuronium, vecuronium or pancuroinium (with efficacy for rocuronium > vecuronium >> pancuronium). Although sugammadex seems like the ideal selective chelating agent for rapid reversal of NMB by the aforementioned agents, I would like to caution critical care anesthesiologists who might care for these patients either in the ICU or OR.

Unplanned reintubations, following general anesthesia administration, are serious adverse events that trigger emergency response systems. Not surprisingly, utilization of intraoperative neuromuscular blockade, despite reversal agents’ administration,   isa significant contributor to the reintubation rate.1-3 Depending on the timing of postoperative respiratory failure, reintubations can either take place in the post anesthesia care unit (PACU) or at various discharge locations, including the ICU. Following sugammadex administration, there is a recommended 24 hour waiting period in order to reparalyze patients with steroidal NMB drugs (rocuronium or vecuronium).4 This effect may be overcome by higher doses of steroidal NMB drugs but regardless it creates an additional consideration in the midst of an urgent situation. Ignoring the presence of sugammadex in a patient’s system could potentially diminish the success rate of reintubation. This possibility will be higher, especially if reintubation is taking place away from the operating room or PACU, since rapid response team members will not be considering the presence of sugammadex and therefore inadequate paralysis could jeopardize reintubation attempts.

Drug interactions are another area of concern when it comes to sugammadex. Drugs that can potentiate neuromuscular blockade such as magnesium and aminoglycosides can counteract the effect of sugammadex and therefore a larger dose may be required. Considering this new era of surgical home initiatives and utilization of different multimodal approaches to improve recovery, including intraoperative magnesium infusions, this issue needs to be considered more carefully. Underdosing of sugammadex may lead to increased risk of recurrence of NMB in the postoperative period.

One problem of particular concern in critically ill patients concerns the elimination of sugammadex, which relies on renal excretion. In patients with substantial renal impairment, the elimination half-life of sugammadex and rocuronium are increased by factors of 15 and 2.5, respectively.5 Likewise, clearance of sugammadex and rocuronium by dialysis is unpredictable. As a result, recommendations state that sugammadex should not be used in patients with creatinine clearance less than 30 mL/min. This makes it problematic in critically ill patients with renal dysfunction, especially those requiring renal-replacement therapy.

Although sugammadex is known to be well-tolerated, practitioners should be aware of a rare but serious side effect. Upper airway obstruction with compete adduction of vocal cords upon administering sugammadex was observed in a group of 9 patients, in 2016.6 Repetitive upper airway obstruction on each of these patients was short lived and was recorded via fiberoptic exam. Similar findings were observed in an earlier case report by Curtis et al. in 2012, when sugammadex was used in a “can’t intubate can’t ventilate” situation in which neuromuscular junction recovery was observed but ventilation was still, briefly, not observed.7 In all these instances, laryngospasm was considered to be a side effect of sugammadex. Bradycardia and severe bradycardia with cardiac arrest have been reported in post market experience with sugammadex, usually observed within minutes of administration.

Anaphylaxis is another side effect worth mentioning, with several case reports to date.8-11 The Japanese Society of Anesthesiologists recently issued a warning about sugammadex-induced anaphylactic shock, due to five episodes observed since March 2010. This might also be attributed to the fact that Japan has the largest number of sugammadex utilizations, followed by Spain.8-10 Sugammadex-induced anaphylaxis typically presents when the patient is already extubated and is being transferred to their hospital bed, the PACU, ICU, etc.11, 12 In these cases emergency re-intubation outside the operating room may be required, which brings me back to my aforementioned comment on repetitive rocuronium administration after sugammadex. Overall, while this novel medication may have several potential benefits, its use in critically ill patients should be approached with caution.

References:

  1. Ramachandran SK, Nafiu OO, Ghaferi A, et al. Independent predictors and outcomes of unanticipated early postoperative tracheal intubation after nonemergent, noncardiac surgery. Anesthesiology 2011;115:44–53.
  2. Lin HT, Ting PC, Chang WY, et al. Predictive risk index and prognosis of postoperative reintubation after planned extubation during general anesthesia: A single-center retrospective case-controlled study in Taiwan from 2005 to 2009. Acta Anaesthesiologica Taiwanica 2013l;51:3-9.
  3. Geater AF, McNeil EB, Vasinanukorn P, et al. Risk factors for reintubation in the post-anaesthetic care unit: a case–control study. Br J Anaesth 2012;109(4):636–642.
  4. Kusha N, Roshan Singh D, Parhasarathy S, et al. Sugammadex: A revolutionary drug in neuromuscular pharmacology. Anesthesia: Essays and Researches 2013;7(3): 302-306.
  5. Staals LM, Snoeck MM, Hunter JM, et al. Pharmacokinetics of rocuronium and sugammadex in patients with normal and impaired renal function. Preseted at: 13th World Congress of Anesthetists, Cape Town, South Africa, March 2-7 2008.
  6. McGuire B, Dalton AJ. Sugammadex, airway obstruction, and drifting across the ethical divide: a personal account.  Anaesthesia 2016;71(5):1365-2044.
  7. Curtis R, Lomax S, Patel B. Use of sugammadex in a ‘can't intubate, can't ventilate’ situation. Br J Anaesth 2012;108:612–4.
  8. Tsur A, Kalansky A. Hypersensitivity associated with sugammadex administration: a systematic review. Anaesthesia 2014;69(11):1251–1257.
  9. Yamada Y, Yamamoto T, Tanabe K2, Fukuoka N, Takenaka M, Iida H. A case of anaphylaxis apparently induced by sugammadex and rocuronium in successive surgeries. J Clin Anesth. Epub 2016 Mar 22.
  10. Ho G, Clarke RC, Sadleir PH, Platt PR.  The first case report of anaphylaxis caused by the inclusion complex of rocuronium and sugammadex.  AA Case Rep 2016 Nov 1;7(9):190-192.
  11. Galvao VR, Giavina-Bianchi P, Castells M. Perioperative anaphylaxis. Curr Allergy Asthma Rep 2014;14(8):452.
  12. Takazawa T, Tomita Y, Yoshida N, et al. Three suspected cases of sugammadex-induced anaphylactic shock. BMC Anesthesiol. 2014;14:92.