Non-IgE-dependent hypersensitivity to rocuronium reversed by sugammadex:

A report of three cases and hypothesis on the underlying mechanism.

David Spoerl; Stéphanie D’Incau; Pascale Roux-Lombard; Thomas Harr; Christoph Czarnetzki

Int. Archives of Allergy and Immunology. 2016; 169:256–262. DOI: 10.1159/000446182

Published online: May 31, 2016

Abstract

​We present 3 cases of pseudoallergic (anaphylactoid) reactions to perioperatively administered rocuronium, which rapidly resolved after sugammadex injection. Allergological workup showed no evidence for immediate-type hypersensitivity to the drugs used for anesthesia, including rocuronium.

However, rocuronium induced an irritative reaction in skin tests in all 3 patients and in 3 healthy individuals. This reaction was specifically suppressed by adding sugammadex at a 1: 1 molecular proportion to rocuronium before the skin tests.

This observation suggests that the patients suffered from a pseudoallergic reaction, and indicates that sugammadex might act via the inhibition of non-IgE mediated MRGPRX2 (Mas-related G-protein-coupled receptor member X2)- triggered mast cell degranulation induced by rocuronium.

Established facts

• Rocuronium has been shown to activate the MRGPRX2 receptor on mast cells, inducing a non- IgEmediated histamine release, which explains its potential for causing pseudoallergic reactions.

• Sugammadex has been designed to encapsulate rocuronium and specifically antagonize its pharmaceutical effects.

• There are several case reports describing the reversal of rocuronium-induced anaphylaxis by the injection of sugammadex; however, the exact pathophysiological mechanism is still unknown.

Novel insights

• Sugammadex was successfully used in 3 patients to rapidly reverse ongoing pseudoallergic reactions.

• Sugammadex abolished the rocuronium-induced irritative skin test reaction in the 3 patients and in 3 healthy individuals, suggesting that this effect might be mediated by the inhibition of rocuroniuminduced MRGPRX2 activation.