Past Uneventful Anesthesia Does Not Exclude Malignant Hyperthermia Susceptibility

A retrospective study of 289 patients diagnosed with malignant hyperthermia has found that approximately 20 percent had previously undergone uneventful general anesthesia with volatile anesthetics prior to developing the condition. The analysis, based on records from a large institutional database, indicates that having tolerated volatile anesthetics in past surgical procedures is insufficient evidence to rule out susceptibility to the disorder.

Malignant hyperthermia is a pharmacogenetic disorder triggered by exposure to volatile anesthetics or depolarizing muscle relaxants. While an individual patient’s anesthetic history serves as an important clue during preoperative evaluation to identify potential susceptibility, its clinical significance has remained incompletely understood, particularly within Asian populations.

To evaluate the relationship between exposure history and onset, researchers reviewed records from 621 patients registered in the database. The analysis included patients with a Clinical Grading Scale score of 35 or higher, leaving 436 patients who met the inclusion criteria. Among these individuals, 289 cases had identifiable anesthetic histories that allowed investigators to evaluate clinical characteristics, preoperative findings, family history, and the exact number of exposures to volatile anesthetics prior to the onset of malignant hyperthermia.

Across the 289 cases with identifiable histories, malignant hyperthermia developed during the initial exposure to volatile anesthetics in 232 patients, representing 80 percent of the cohort. In contrast, the condition emerged during a second exposure in 36 patients, or 12 percent, and after three or more exposures in 21 patients, or 7 percent. Across the entire sample, the mean number of exposures before onset was 1.37, with a maximum of 11 exposures documented.

Investigators divided patients who developed malignant hyperthermia into two groups based on whether onset occurred during the initial exposure or following prior uneventful exposures, performing multivariable logistic regression to compare the timing of onset. The odds of malignant hyperthermia occurring at the first exposure were higher in cases occurring in or before 1984 (odds ratio 2.75, 95% confidence interval 1.10 to 6.86, P = 0.03) and during the 1985 to 1994 period (odds ratio 2.89, 95% confidence interval 1.30 to 6.41, P = 0.01), compared with cases occurring in or after 1995. Age, sex, and the use of succinylcholine were not statistically significant factors.

The study authors concluded that although anesthetic history remains an essential component of preoperative clinical evaluation, a record of previous uneventful exposure to volatile anesthetics does not exclude malignant hyperthermia susceptibility. They noted that these findings underscore the continuous need for careful and comprehensive preoperative assessments.

Subject of Research: Exposure history to volatile anesthetics in patients with malignant hyperthermia

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

Article References: Sumii, A., Xia, G., Otsuki, S., Ikeda, T., Ishii, T., Sasai, K., Yeh, H.-M., Chen, P.-L., Ichihara, Y., Mukaida, K., Tsutsumi, Y. M., & Miyoshi, H. (2026). Exposure history to volatile anesthetics in patients with malignant hyperthermia: a retrospective analysis of 289 cases. BMC Anesthesiology. https://doi.org/10.1186/s12871-026-04390-x

Image Credits: AI Generated

DOI: 10.1186/s12871-026-04390-x

Keywords: malignant hyperthermia, volatile anesthetics, anesthesia history, pharmacogenetic disorders, preoperative assessment, Clinical Grading Scale, succinylcholine, Exposure, history, volatile, anesthetics, patients