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Malignant hyperthermia

M Denborough1

  • 1Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra ACT. M.Denborough@anu.edu.au

Lancet (London, England)
|November 3, 1998
PubMed
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Malignant hyperthermia (MH) is a dangerous inherited muscle disorder. Research shows increased muscle calcium ions cause MH, leading to better diagnosis and a dantrolene treatment that has drastically reduced mortality.

Area of Science:

  • Muscle physiology
  • Anesthesiology
  • Human genetics

Background:

  • Malignant hyperthermia (MH) is a severe hypermetabolic complication associated with anesthesia and other triggers.
  • A specific inherited muscle membrane disorder predisposes individuals to MH.
  • Inbred pigs serve as a valuable animal model for studying MH.

Observation:

  • The primary biochemical abnormality in MH is elevated calcium ion concentration within muscle cells.
  • MH susceptibility can be triggered by specific anesthetic agents, severe exercise, infections, and certain drugs.
  • Overheating in infants can also precipitate MH episodes.

Findings:

  • Understanding the role of calcium ions has led to diagnostic muscle tests for MH susceptibility.
  • Dantrolene has been identified as a specific and effective treatment for MH.

Related Experiment Videos

  • Genetic studies in pigs identified a mutation in the ryanodine receptor (RYR) as the cause of MH susceptibility.
  • Human genetics of MH are complex, with RYR mutations identified in only 20% of susceptible families.

    • Implications:

    • The development of diagnostic tests and dantrolene treatment has significantly reduced MH case-fatality rates from 70% to 5%.
    • Further research into the complex human genetics of MH is needed to identify all causative factors.
    • This research improves understanding and management of inherited muscle disorders and anesthetic complications.