A new option for the treatment of anaphylaxis linked to steroidal neuromuscular blockers: How much value should we grant to case reports?

Abstract

Neuromuscular blockers (NMBs) are commonly used in anesthesia to facilitate tracheal intubation and optimize surgical conditions. However, these compounds share a common side effect -the risk of an allergic reaction. Anaphylactic shock is a rare (approximately one case in 10,000-20,000 procedures) but life-threatening complication of anesthesia. 1 In France, various epidemiological studies over the last three decades have shown that the most common causal agents of anaphylaxis are NMBs. 2 In the event of anaphylactic shock, epinephrine is the first-line therapy. The dose is usually titrated -except in case of cardiac arrest -depending on the clinical presentation and based on heart rate and blood pressure, to avoid the occurrence of arrhythmia with large doses of epinephrine. 3 This symptomatic treatment, coupled with crystalloid fluid resuscitation, allows to counteract hemodynamic (decreased blood pressure and cardiac output) and respiratory (bronchoconstriction) effects of the numerous mediators that are released during the course of an anaphylactic reaction. Despite these measures, the outcome remains potentially lethal in approximately 10% of cases. 4 However, there is no specific therapy of NMBassociated anaphylaxis. Proposed therapies could involve a substance able to rapidly inhibit the anaphylactic reaction by masking or binding the causal allergen. A specific therapy for the anaphylactic reaction to dextran, used in some countries as a fluid therapy, was attempted during the 1980s with the arrival on the market of a dextran-inhibitor hapten. 5 This hapten was purported to reduce the allergystimulating effects of dextrans through specific inhibition. The effectiveness of this preventive strategy proved unreliable, notwithstanding the other adverse effects of dextrans, renal in particular. 6 Thus, there remains no specific strategy at this time regarding the prevention or treatment of allergic reactions to NMBs. Could this situation change with the recent availability of sugammadex? Sugammadex is a gammacyclodextrine that was modified by the addition of side chains that specifically encapsulate the steroidal core of the NMB, mainly through interactions between the negative charges of the cyclodextrine molecule and the positive charges of the quaternary ammonium ions. 7 Their binding at the centre of the cyclodextrine molecule, more specifically the sterol moiety, is strong and prolonged, implying the presence of various high-energy chemical bonds. Binding is rapid, and steroidal NMBs show a high affinity for sugammadex, especially rocuronium and to a lesser degree vecuronium. 8 Beyond the rapid reversal of NMBs allowed by sugammadex, 7 neutralizing the NMB molecules by masking the causal allergen (i.e., the quaternary ammonium ion) should also be considered when an NMB-related allergic event is suspected. This hypothesis was reported for the first time through a case report. 9 The authors of that report described a serious anaphylactic reaction that occurred immediately after an induction sequence that i...

A Short Update on Sugammadex with a Special Focus on Economic Assessment of its Use in North America

“…Via its peculiar action, sugammadex has been suggested as a novel treatment therapy to inhibit mast cells and basophils activation triggering anaphylaxis. This hypothesis was confirmed by evidence from several case reports describing hemodynamic and respiratory restoration few minutes after sugammadex administration [62]. However, a recent case report described the inefficacy of low doses of sugammadex to reverse rocuronium-induced anaphylaxis [65].…”

“…Its incidence in anesthesia is estimated to range from 1 in 10000 to 1 in 20000 cases [62]. In anesthesia, the drugs inducing more frequently an anaphylactic reaction are the NMBA with the following incidence: succinylcholine (61%), atracurium (19.5%), cisatracurium (6%), vecuronium (4.5%), rocuronium (4%), pancuronium (3%), and mivacurium (2%) [63].…”

Sugammadex: An Update

“…After 19 minutes of ineffective traditional management, 500 mg sugammadex was administered with immediate haemodynamic improvement. The mechanism of this beneficial effect is unknown, however, in view of its own potential for causing anaphylaxis, a risk benefit ratio should be considered before treating rocuronium-induced anaphylaxis with sugammadex [12].…”

Publishing in science: a collaborative process

“…3 Mon espoir est que cet éditorial apportera quelques conseils préliminaires aux auteurs potentiels ainsi qu'aux investigateurs planifiant un travail qu'ils espèrent voir publier. De même, les réviseurs peuvent l'utiliser pour identifier quels éléments prendre en compte pour leurs propres lectures.…”

“…3 My hope is that this editorial will provide some preliminary guidance to prospective authors and also to investigators planning work that they hope will eventually be published. Reviewers, as well, can refer to this article when considering elements to take into account in their own reading.…”