The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model*

Abstract

SummaryThe availability of sugammadex as a selective encapsulating agent for rocuronium has led to speculation that it may be useful in mitigating rocuronium-induced anaphylaxis. Off-label use of sugammadex for this indication has already been documented in case reports although there are theoretical objections to the likelihood of an allergen-binding agent's being able to attenuate the immunological cascade of anaphylaxis. Using a cutaneous model of anaphylaxis in rocuronium-sensitised patients, we were unable to demonstrate that sugammadex was effective in attenuating the type-1 hypersensitivity reaction after it has been triggered by rocuronium, but we were able to demonstrate that these patients are anergic to sugammadex-bound rocuronium. These findings demonstrate that a cyclodextrin can bind an allergen and exclude it from interacting with the immune system, and may potentially lead to novel applications in other allergic diseases. However, there is no evidence that sugammadex should be used for the treatment of rocuronium-induced anaphylaxis, and clinical management should follow established protocols. Accepted: 23 October 2011In many countries neuromuscular blocking drugs are the most common agents responsible for anaphylaxis during general anaesthesia, with rocuronium being one of the most frequently implicated [1,2]. One of the basic principles in the management of anaphylaxis is the removal of the triggering agent [3]. However, although there is evidence that the removal of an allergen from its corresponding cell-bound-specific antibody will attenuate the process of mediator release from the mast cell in vitro [4], there is no evidence that it will alter the clinical course of anaphylaxis in vivo.Sugammadex is a modified c-cyclodextrin with a hydrophobic cavity designed to encapsulate rocuronium and other steroid-based neuromuscular blocking drugs [5]. Intermolecular (van der Waals) forces result in a water-soluble complex with a high association rate. When used for the reversal of rocuronium-induced neuromuscular blockade, sugammadex is very effective [6]. Sugammadex is rapidly distributed to the effect compartment [7], its affinity for rocuronium is greater than that of the nicotinic acetylcholine receptor [8], and the influence of rocuronium at the nicotinic acetylcholine receptor is both reversible and relatively insensitive [9]. Consequently, sugammadex has been shown to reverse profound rocuronium-induced neuromuscular blockade within minutes [6].

A reply

“…Our findings gave us no alternative but to conclude that 'sugammadex is unlikely to modify significantly the clinical course of an established allergic reaction', as they do not support a role for sugammadex in the modification of an established allergic response [1]. Baldo cites several case reports that suggest a role for sugammadex in modifying an allergic response, but none of these prove a role, because anaphylaxis varies in its severity and is self-terminating in most cases, and there are plausible alternative explanations in each case [1].…”

“…We read with great interest the metaanalysis of Yin and Ho regarding the use of plethysmographic variability index (PVI) to predict fluid responsiveness [1]. The authors concluded that PVI had a reasonable ability to predict preload responsiveness in peri-operative patients.…”

Effect of sugammadex and neostigmine on tracheal muscle: In vitro study

“…Their and our similar results support that sugammadex gives similar muscle responses in trachea and bronchus. In addition, laryngospasm ,bronchospasm and anaphylaxis related sugammadex were reported in a few clinical data [16][17][18][19][20][21][22][23][24][25][26][27]. Absence of tracheal tissue response in our study suggests that these clinical conditions related with other mechanisms except the tracheal tissue response.…”

Sugammadex, rocuronium and mast cell numbers in the rat liver

“…We were interested to read about the effects of rocuronium and sugammadex on rat livers by Tomak et al [1], but are concerned that they misrepresented the findings of the study by Clarke et al [2] who used an in-vivo human model of IgEmediated anaphylaxis that demonstrated that patients were anergic to sugammadex-bound rocuronium. However, there was no attenuation in the wheal-and-flare response when sugammadex was administered after the reaction had commenced.…”