title: In-vitro contracture testing for susceptibility to malignant hyperthermia: can halothane be replaced?
abstract: BACKGROUND
  Malignant hyperthermia is a potentially lethal inherited hypermetabolic syndrome that develops in susceptible individuals following administration of depolarising neuromuscular relaxants or volatile anaesthetics. Genetic analysis can only confirm a diagnosis of malignant hyperthermia in about 70%, and in the remainder an in-vitro contracture test, with halothane and caffeine, on muscle obtained from open muscle biopsy is required to establish the diagnosis. As the licence for clinical use of halothane expired in 2005, its continuing availability is in doubt. More modern volatile anaesthetics such as enflurane, isoflurane, desflurane and sevoflurane are less potent triggers of malignant hyperthermia in humans and pigs. The aim of this study was to investigate whether these agents can be considered possible substitutes for halothane in a modified in-vitro contracture test.
  
  
  METHODS
  With institutional review board approval and prior written consent, muscle bundles of 30 patients with a personal or family history of malignant hyperthermia were investigated. Of these, 13 were diagnosed malignant hyperthermia susceptible and 17 nonsusceptible. Surplus muscle was tested with increasing concentrations of enflurane, isoflurane, desflurane and sevoflurane.
  
  
  RESULTS
  There were no differences in weight, length or predrug tension of the muscle bundles. At increasing concentration, all volatile anaesthetics except sevoflurane induced significantly greater contractures in malignant hyperthermia susceptible compared to malignant hyperthermia nonsusceptible muscle. In malignant hyperthermia susceptible muscle bundles, halothane led to significantly higher contractures compared to the other investigated substances.
  
  
  CONCLUSIONS
  Halothane was the strongest discriminator for malignant hyperthermia in the in-vitro contracture tests. It remains the ideal substance for diagnostic testing and cannot simply be replaced by other agents in this test.
authors.affiliation: Department of Anaesthesiology, University Würzburg, Würzburg, Germany. tom.metterlein@gmx.net
authors.forename: Thomas
authors.initials: T
authors.lastname: Metterlein
authors.forename: Frank
authors.initials: F
authors.lastname: Schuster
authors.forename: Peter
authors.initials: P
authors.lastname: Kranke
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Martin
authors.initials: M
authors.lastname: Anetseder
mesh_terms: D018685:Anesthetics, Inhalation; D001706:Biopsy; D016022:Case-Control Studies; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004737:Enflurane; D006221:Halothane; D006801:Humans; D007530:Isoflurane / Q000031:analogs & derivatives; D008305:Malignant Hyperthermia / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D008738:Methyl Ethers; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D011237:Predictive Value of Tests; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D004737:Enflurane; D000077335:Desflurane; D007530:Isoflurane; D006221:Halothane