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Ondansetron-induced muscular contractures in malignant hyperthermia-susceptible individuals

Stephan Johannsen1, Norbert Roewer, Frank Schuster

  • 1Department of Anaesthesia and Critical Care, University of Wuerzburg, Wuerzburg, Germany.

Anesthesia and Analgesia
|June 15, 2012
PubMed
Abstract

Insights

Ondansetron caused muscle contractures in vitro, particularly in malignant hyperthermia-susceptible (MHS) individuals. However, the high concentrations required suggest ondansetron is unlikely to trigger malignant hyperthermia in patients.

Area of Science:

  • Pharmacology
  • Anesthesiology
  • Muscle Physiology

Background:

  • Ondansetron, a 5-HT3 receptor antagonist, is used for nausea and vomiting.
  • A fatal case linked ondansetron to malignant hyperthermia (MH).

Purpose of the Study:

  • To investigate the in vitro effect of ondansetron on muscle specimens from MH-susceptible (MHS) and MH-nonsusceptible (MHN) individuals.

Main Methods:

  • Muscle bundles from 6 MHS and 10 MHN patients were exposed to varying ondansetron concentrations (0.1–300 μg/mL) in a tissue bath.
  • Resting tension and twitch height were continuously monitored.

Main Results:

  • Ondansetron induced increasing twitch amplitudes in both MHS and MHN muscle bundles.
  • Significant contractures developed in MHS muscle at 50 and 100 μg/mL ondansetron, but not in MHN muscle.
  • At 300 μg/mL, muscular response occurred in MHN muscle, but was significantly lower than in MHS muscle.

Conclusions:

  • Ondansetron induced in vitro contractures in skeletal muscle, with a significantly greater effect in MHS muscle.
  • The concentrations needed to induce contractures were substantially higher than therapeutic plasma levels.
  • Ondansetron is unlikely to be a trigger for malignant hyperthermia in vivo.

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