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March 9, 2018

Perioperative Anaphylaxis

Question

Can Sugammadex be used to manage an allergic reaction suspected to arise from administration of Rocuronium?

Answer

By WAO Ask the Expert website editors

Neuromuscular blocking agents (NMBA) may account for 50-70% of perioperative anaphylaxis, being the most common cause in numerous French studies, while being second to antibiotics in the US and other European countries (1, 2). The anaphylaxis can be either immunologic or nonimmunologic. While succinylcholine, a nonsteroidal NMBA, was the most common NMBA to cause anaphylaxis 10 years ago, more recent studies indicate that Rocuronium, a steroidal NBMA, is equal to succinylcholine as NMBAs causing anaphylaxis, about 1: 2000 to 1: 2500 exposures (3). This is largely due to a shift in the use of steroidal NMBAs, such as which can be easily and quickly reversed with agents such as Sugammadex, a synthetic γ-dextrin derivative that selectively binds to the steroidal NMBA, thereby reversing its neuromuscular blocking effects. Sugammadex has been available internationally for several years but was only FDA approved for use in the US in December 2015.

While effective at reversing the pharmacological effects of Rocuronium, it is unknown how beneficial Sugammadex is at treating NMBA-induced anaphylaxis. Theoretically, the rocurinium-sugammadex complex hides the ammonium group epitope of rocuronium which induces the allergic reaction (4). However, once the allergic cascade is started, it is unknown how effective this epitope encapsulation will be at preventing progression of the allergic reaction (5). A molecular model suggested that hypersensitivity binding could still occur (6). One animal model suggested improvement with the administration of Sugammadex (7) while a cutaneous model did not (8). In at least five female case reports of Rocuronium-induced anaphylaxis treated with Sugammedex, a benefit was described, but the effects of other treatments administered concurrently for the treatment of anaphylaxis may have been the main contributor to the noted improvement (5). It has been postulated that Sugammedex could add benefit during anaphylaxis treatment by relaxing of the neuromuscular blockade of the NMBA with a subsequent positive effect on cardiac preload and afterload (5). When used, a high dose of Sugammedex (16 mg/kg) has been recommended, reassuringly, and no reports of worsening of anaphylaxis have been described.  A retrospective analysis of 13 case reports concluded that Sugammedex does not modify the course of an anaphylactic reaction and the authors warned against adding this drug to the anaphylaxis treatment algorithm (9). However, the use of Sugammedex should not replace first line treatment of any anaphylactic reaction, regardless of the cause: epinephrine, IV fluids, oxygen, and general supportive care. However, ironically, Sugammadex, itself, in the absence of an NMBA allergic reaction, has been reported to induce anaphylaxis at the rate of 29/million exposures (3).

References

1. Laxenaire MC. [Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996)]. Ann Fr Anesth Reanim. 1999;18(7):796-809

2. Mertes PM, Alla F, Trechot P, Auroy Y, Jougla E, Groupe d'Etudes des Reactions Anaphylactoides P. Anaphylaxis during anesthesia in France: an 8-year national survey. J Allergy Clin Immunol. 2011;128(2):366-73

3. Takazawa T, Mitsuhata H, Mertes PM. Sugammadex and rocuronium-induced anaphylaxis. J Anesth. 2016;30(2):290-7

4. Jones PM, Turkstra TP. Mitigation of rocuronium-induced anaphylaxis by sugammadex: the great unknown. Anaesthesia. 2010;65(1):89-90; author reply

5. Schaller SJ, Fink H. Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid. 2013;8:57-67

6. Baldo BA, McDonnell NJ, Pham NH. The cyclodextrin sugammadex and anaphylaxis to rocuronium: is rocuronium still potentially allergenic in the inclusion complex form? Mini Rev Med Chem. 2012;12(8):701-12

7. Tomak Y, Yilmaz A, Bostan H, Tumkaya L, Altuner D, Kalkan Y, et al. Effects of sugammadex and rocuronium mast cell number and degranulation in rat liver. Anaesthesia. 2012;67(10):1101-4

8. Clarke RC, Sadleir PH, Platt PR. The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model. Anaesthesia. 2012;67(3):266-73

9. Platt PR, Clarke RC, Johnson GH, Sadleir PH. Efficacy of sugammadex in rocuronium-induced or antibiotic-induced anaphylaxis. A case-control study. Anaesthesia. 2015;70(11):1264-7


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