Pre-operative exercise and pyrexia as modifying factors in malignant hyperthermia (MH)

Neuromuscul Disord. 2022 Aug;32(8):628-634. doi: 10.1016/j.nmd.2022.06.003. Epub 2022 Jun 11.


Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anesthetics and succinylcholine. MH is caused by mutations in the skeletal muscle ryanodine receptor (RYR1) gene, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between the prevalence of risk genotypes and actual MH incidence remains unexplained. We investigated the role of pre-operative exercise and pyrexia as potential MH modifying factors. We included cases from 5 MH referral centers with 1) clinical features suggestive of MH, 2) confirmation of MH susceptibility on Contracture Testing (IVCT or CHCT) and/or RYR1 genetic testing, and a history of 3) strenuous exercise within 72 h and/or pyrexia >37.5 °C prior to the triggering anesthetic. Characteristics of MH-triggering agents, surgery and succinylcholine use were collected. We identified 41 cases with general anesthesias resulting in an MH event (GA+MH, n = 41) within 72 h of strenuous exercise and/or pyrexia. We also identified previous general anesthesias without MH events (GA-MH, n = 51) in the index cases and their MH susceptible relatives. Apart from pre-operative exercise and/or pyrexia, trauma and acute abdomen as surgery indications, emergency surgery and succinylcholine use were also more common with GA+MH events. These observations suggest a link between pre-operative exercise, pyrexia and MH.

Keywords: (Exertional) rhabdomyolysis; Malignant hyperthermia; RYR1.

MeSH terms

  • Fever* / complications
  • Humans
  • Malignant Hyperthermia* / etiology
  • Malignant Hyperthermia* / genetics
  • Malignant Hyperthermia* / physiopathology
  • Mutation
  • Preoperative Exercise* / physiology
  • Ryanodine Receptor Calcium Release Channel* / genetics
  • Succinylcholine / adverse effects


  • RYR1 protein, human
  • Ryanodine Receptor Calcium Release Channel
  • Succinylcholine