Hypersensitivity Reactions to Neuromuscular Blocking Agents

Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3 000 to 1 in 110 000 general anaesthetics. However striking variations have been reported among countries. The mechanism of sensitisation seems to implicate the presence of a substituted ammonium ion in the molecule. Due to lack of exposure prior to the reaction in a large number of reactors, it has been hypothesised that sensitisation may involve other, as yet undefined, substituted (quaternary and tertiary) ammonium ion containing compounds such as pholcodine, present in the environment of the patient. This hypothesis is still under investigation. The mechanism of non-IgE mediated hypersensitivity reactions is less well known. Identified mechanisms correspond to direct histamine release or interactions with muscarinic and nicotinic receptors. Allergic reactions cannot be clinically distinguished from non-IgE-mediated reactions. Therefore, any suspected hypersensitivity reaction must be investigated using combined pre and postoperative testing. Because of the frequent but not systematic cross-reactivity observed with muscle relaxants, every available neuromuscular blocking agent should be tested, using intradermal tests to confirm the responsibility of the suspected drug which should be definitely excluded. Cross-sensitivity investigation will also try to identify the safety of drugs that can be potentially used in future anaesthesia. The determination of basophil activation investigations using direct leukocyte histamine release test or flow cytometry would be of particular interest to investigate cross sensitisation in complement to skin tests. There is no demonstrated evidence supporting systematic pre-operative screening in the general population at this time. However, since no specific treatment has been shown to reliably prevent anaphylaxis, allergy assessment must be performed in all high-risk patients. In view of the relative complexity of allergy investigation, and of the differences between countries, an active policy to identify patients at risk and to provide any necessary support from expert advice to anaesthetists and allergologists through the constitution of allergo-anaesthesia centres in every country should be promoted.