Mitigation of rocuronium-induced anaphylaxis by sugammadex: the great unknown

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Intra-operative anaphylaxis has been estimated to occur in between 1 in 3500 and 1 in 13 000 cases [1]. Neuromuscular blocking drugs account for 55–69% of cases of peri-operative anaphylaxis, and the most commonly-implicated drugs are suxamethonium and rocuronium [2, 3]. Rocuronium-induced anaphylaxis is probably more common in certain countries, such as France and Norway, than it is in North America [1, 4].

The treatment of anaphylaxis is familiar to all anaesthetists [1]. Anaphylaxis is not an all-or-nothing phenomenon, and the continued anaphylactic response may rely, to an extent, upon the continued presence in the body of the culprit antigen [5]. Consequently, a standard treatment involves the prompt elimination of ongoing patient exposure to the offending antigen [1, 5]. In the case of most intravenous drugs, it is impossible to eliminate exposure to the drug that is already in the patient’s blood, and the remaining drug may continue to sustain the anaphylactic response until its elimination by the body.

In the case of rocuronium-induced anaphylaxis, there may exist a novel treatment strategy that aims to prevent propagation of the anaphylactic response by rocuronium molecules already in the patient’s blood. By administering sugammadex (a novel selective binding agent that avidly encapsulates rocuronium [6]), it may be effectively possible to ‘remove’ free rocuronium molecules from the circulation, and hence slow down or halt the immunologic process. Of course, this speculation relies upon the assumption that sugammadex-bound rocuronium will no longer initiate cross-linking of cell-bound IgE, which may be true given that sugammadex almost completely encapsulates the rocuronium molecule [6]. This encapsulation may disrupt the structural orientation of rocuronium that is necessary to cause IgE cross-linkage, and hence, disrupt propagation of anaphylaxis.

Several aspects of this potential treatment need to be considered. First, the antigenic portion of the rocuronium molecule containing the ammonium group actually protrudes from the sugammadex molecule [6]. This may mean that the portion of the rocuronium molecule responsible for IgE cross-linkage (and thus anaphylaxis) may still be able to contact (and cross-link) IgE. Second, since sugammadex binds aminosteroid molecules, there is a theoretical potential for sugammadex to bind other steroid molecules (such as the corticosteroids universally used to treat anaphylactic reactions), which would be undesirable. However, sugammadex has exhibited an affinity for other steroid compounds (such as aldosterone, cortisone, or hydrocortisone) that is at least 120 times lower than its affinity for rocuronium [7]. The clinical importance of this potential interaction is unknown.

Although a case of treatment of rocuronium-induced anaphylaxis by sugammadex has not been described, there may be sufficient pharmacologic and pathophysiologic rationale to consider administration of sugammadex to a patient with anaphylaxis if traditional treatment is failing and there is a high index of suspicion of rocuronium being the causative agent. Since the goal of administering sugammadex in this context would be to bind all molecules of rocuronium as quickly as possible, the dose of sugammadex required may well be high (up to 16 mg.kg−1 [8], depending on the dose of rocuronium given). It is important to stress that administering sugammadex in this circumstance would be an off-label, unapproved indication, and that the first priority of treatment of any suspected anaphylactic reaction should be the implementation of well-established therapies [1] with consideration of other options, only if these therapies do not prove effective.

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