Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis

Anesthesiology. 2001 Jan;94(1):95-100. doi: 10.1097/00000542-200101000-00019.


Background: Malignant hyperthermia (MH), heat stroke, and exercise-induced rhabdomyolysis (ER) were suspected to be related syndromes. However, it is not known whether individuals with history of ER have an increased incidence of susceptibility to MH. To establish an association between ER and susceptibility to MH, the authors determined the MH status in patients with a history of MH-like episodes induced by physical stress.

Methods: Twelve unrelated patients with ER, 18 patients with anesthesia-induced MH, and 28 controls were investigated with the in vitro contracture test (IVCT) according to the European MH Group protocol and the ryanodine contracture test. In addition, all patients were screened for genetic mutations, and histology was performed on muscle specimens.

Results: Ten ER patients had positive IVCT results, one patient had a negative test result, and one patient showed equivocal responses. Samples from patients with positive IVCT results showed pronounced contractures after exposition to ryanodine, as opposed to specimens from patients with negative IVCT results, which developed contractures slowly. Three ER patients had mutations at the ryanodine receptor gene. All anesthesia-induced MH patients had positive IVCT results, two of them presented the C1840T mutation. The control patients had normal contracture test results and no typical MH mutations. Histologic examination determined no specific myopathies in any patient.

Conclusions: Regarding these results, the authors recommend performing muscle biopsies for histologic examination and IVCT in patients with ER. In addition, the patient should be seen by a neurologist and screened for genetic abnormalities to shed light on the genetics of MH.

MeSH terms

  • Adolescent
  • Adult
  • Anesthetics, Inhalation / adverse effects
  • Case-Control Studies
  • Child
  • Disease Susceptibility*
  • Exercise*
  • Halothane / adverse effects
  • Humans
  • Male
  • Malignant Hyperthermia / genetics*
  • Muscle Contraction / drug effects
  • Muscle, Skeletal / pathology
  • Polymerase Chain Reaction
  • Rhabdomyolysis / etiology*
  • Ryanodine / pharmacology


  • Anesthetics, Inhalation
  • Ryanodine
  • Halothane