mivacurium and Anaphylaxis

Anaphylactic reactions to anaesthetic and associated agents used during the perioperative period have been reported with increasing frequency in most developed countries. Any drug administered in the perioperative period can potentially produce life-threatening immune-mediated anaphylaxis. Most published reports on the incidence of anaphylaxis come from France, Australia, the UK and New Zealand. These reflect an active policy of systematic clinical and/or laboratory investigation of suspected immune-mediated reactions. The estimated incidence of anaphylaxis ranges from 1:10,000 to 1:20,000. Muscle relaxants (69.1%) and latex (12.1%) were the most frequently involved drugs according to the most recent French epidemiological survey. Clinical symptoms do not afford an easy distinction between immune-mediated anaphylactic reactions and anaphylactoid reactions resulting from direct non-specific histamine release. Moreover, when restricted to a single clinical symptom, anaphylaxis can easily be misdiagnosed. Pre- and postoperative investigation must be performed to confirm the nature of the reaction, the responsibility of the suspected drugs and to provide precise recommendations for future anaesthetic procedures. These include plasma histamine, tryptase and specific IgE concentration determination at the time of the reaction and at skin tests 6 weeks later. In addition, since no specific treatment has been shown reliably to prevent the occurrence of anaphylaxis, allergy assessment must be performed in all high-risk patients. Treatment of anaphylaxis is aimed at interrupting contact with the responsible antigen, inhibiting mediator production and release, and modulating the effects of released mediators. It must be initiated as quickly as possible and relies on widely accepted principles. Finally, the need for proper epidemiological studies and the relative complexity of allergy investigation should be underscored. They represent an incentive for further development of allergo-anaesthesiology clinical networks to provide expert advice for anaesthetists and allergologists.

Topics: Anaphylaxis; Anesthetics; Epinephrine; Histamine Release; Humans; Hypnotics and Sedatives; Immunoglobulin E; Isoquinolines; Latex Hypersensitivity; Mivacurium; Neuromuscular Nondepolarizing Agents; Preoperative Care; Risk Factors; Skin Tests

Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children.. MAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro.. Mivacurium caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in Kit. Mivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.

Topics: Anaphylaxis; Animals; Calcium; Cell Degranulation; Cell Line; Cytokines; Drug-Related Side Effects and Adverse Reactions; HEK293 Cells; Histamine; Humans; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Mivacurium; Receptors, G-Protein-Coupled

Topics: Anaphylaxis; Child; Chymases; Humans; Inflammation Mediators; Isoquinolines; Male; Mivacurium; Neuromuscular Nondepolarizing Agents; Serine Endopeptidases; Tryptases

Topics: Adult; Anaphylaxis; Atracurium; Drug Hypersensitivity; Female; Humans; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Skin Tests