Exposure history to volatile anesthetics in patients with malignant hyperthermia: a retrospective analysis of 289 cases

Abstract Background: Malignant hyperthermia (MH) is a pharmacogenetic disorder triggered by exposure to volatile anesthetics or depolarizing muscle relaxants. Although anesthetic history is an important clue for identifying MH susceptibility, its clinical significance remains incompletely understood, particularly in Asian populations. Methods: We retrospectively analyzed data from a large institutional MH database. Patients with a Clinical Grading Scale (CGS) score ≥35 were included. Clinical characteristics, anesthetic history, family history, and preoperative findings were collected. Among patients with identifiable anesthetic histories, the number of exposures to volatile anesthetics prior to MH onset was evaluated. Patients were divided into two groups based on whether MH occurred at the first exposure or after previous uneventful exposures. Among patients who developed MH, multivariable logistic regression analysis was performed to compare the timing of MH onset-specifically evaluating factors associated with MH occurring at the first exposure versus after previous uneventful exposures to volatile anesthetics. Results: Of 621 registered patients, 436 met the inclusion criteria, and 289 had identifiable anesthetic histories. MH occurred at the first exposure to volatile anesthetics in 232 patients (80%), at the second exposure in 36 patients (12%), and after three or more exposures in 21 patients (7%). The mean number of exposures before MH onset was 1.37 (maximum 11). Approximately 20% of MH patients had undergone previous uneventful anesthesia with volatile anesthetics. In the multivariable analysis comparing the timing of MH onset among patients with MH, the odds of MH occurring during the first exposure to volatile anesthetics were higher in cases occurring in or before 1984 (OR 2.75, 95% CI 1.10–6.86, P = 0.03) and in those occurring during 1985-94 (OR 2.89, 95% CI 1.30–6.41, P = 0.01), compared with cases occurring in or after 1995 (reference category). Age, sex, and succinylcholine use were not significant factors. Conclusions: Although anesthetic history is an important component of preoperative evaluation, approximately 20% of patients with MH in our cohort had experienced one or more previous uneventful exposures to volatile anesthetics before developing MH. These findings indicate that uneventful anesthesia should not be considered sufficient to exclude MH susceptibility, underscoring the need for careful and comprehensive preoperative assessment.