Impact of Closely Grouped, Iterative Exposures to Suxamethonium During ECT on the Sensitization to NMBA and the Development of Protective Antibodies

Acute per-anesthetic hypersensitivity reaction (HSA-PA) is a rapidly occurring systemic reaction following injection of a drug during anesthesia (mortality between 3 and 9%). The substances responsible for these reactions in France are Neuro-Muscular Blocking Agents (NMBA) in 60% of cases. The main mechanism mentioned is an immediate systemic hypersensitivity immune reaction (anaphylaxis). The mechanism of immunization to NMBA is not yet understood. Electroconvulsive therapy (ECT) is a long-standing therapeutic approach still widely used today, for its high efficiency, particularly in depressive syndromes resistant to antidepressants. It has an efficacy comparable (or even superior) to pharmacological treatments and improves the mortality associated with this disease. Treatment with iterative ECT sessions includes an attack phase with an average of 12 sessions over 4 weeks, with secondary spacing of sessions before switching to antidepressant treatment. These sessions are carried out in the operating room under general anesthesia, thanks to a hypnotic and a NMBA, suxamethonium, as recently recommended by the French Anesthesiology Society in 2020. ECT therefore represent an interesting model of iterative exposure of a relatively homogeneous population to a single highly sensitizing substance, which could make it possible to study the evolution of sensitization as a function of various factors, in particular cumulative exposure, for which no data is currently available.

Acute per-anesthetic hypersensitivity reaction (HSA-PA) is a rapidly occurring systemic reaction following injection of a drug during anesthesia (mortality between 3 and 9%). The substances responsible for these reactions are different types of Neuro-Muscular Blocking Agents (NMBA) in 60% of cases. The main mechanism mentioned is an immediate systemic hypersensitivity immune reaction (anaphylaxis). Anaphylactic reactions are classically described as IgE-dependent, triggered by the allergen which, by bridging specific IgE antibodies on the surface of mast cells and basophils, induces a massive release, in particular of histamine, which is responsible for the symptoms. Other immunological mechanisms, in particular by specific IgGs, have been described. The mechanism of immunization to Neuro-Muscular Blocking Agents (NMBA) is not yet understood. The quaternary ammonium group (AQ) is the common epitope of NMBA recognized by IgE. Due to the absence of previous exposure to NMBA reported in 50% of patients with HSA-PA to NMBA, other substances carrying substituted AQ ions are suspected of inducing cross-sensitization, such as household cleaners, cosmetics or drug (pholcodine). However, the sensitizing role of NMBA themselves is not established, and no study has analyzed iterative exposure to Neuro-Muscular Blocking Agents (NMBA) as a sensitizing factor. Electroconvulsive therapy (ECT) is a long-standing therapeutic approach still widely used today, for its high efficiency, particularly in depressive syndromes resistant to antidepressants. It has an efficacy comparable (or even superior) to pharmacological treatments and improves the mortality associated with this disease. Treatment with iterative ECT sessions includes an attack phase with an average of 12 sessions over 4 weeks, with secondary spacing of sessions before switching to antidepressant treatment. These sessions are carried out in the operating room under general anesthesia, thanks to a hypnotic and a NMBA, suxamethonium, as recently recommended by the French Anesthesiology Society in 2020. ECT therefore represent an interesting model of iterative exposure of a relatively homogeneous population to a single highly sensitizing substance, which could make it possible to study the evolution of sensitization as a function of various factors, in particular cumulative exposure, for which no data is currently available. A single patient group is planned in this study, consisting of patients with a medical indication for ECT for psychiatric pathologies resistant to medical treatment (depression, mania, hallucinatory episode in particular). The study will take place in two parts: a preliminary phase "phase P" in 10 patients (with previous exposure to ECT) and a "phase E" study phase in 60 patients. For phase E, only patients with first-time access to ECT or without ECT in the previous ten years will be eligible.