title: Sevoflurane is less sensitive than halothane for in vitro detection of malignant hyperthermia susceptibility.
abstract: BACKGROUND
  Sevoflurane is a known triggering agent of malignant hyperthermia (MH). The present study analyzed different effects of sevoflurane on skeletal muscle of MH susceptible and nonsusceptible individuals in vitro and compared the results to the standardized test protocol with halothane and caffeine. A potential influence of a present ryanodine receptor type 1 (RyR1) mutation was investigated.
  
  
  METHODS
  Muscle bundles of 24 MH-susceptible patients with or without an RyR1 mutation, 35 MH-nonsusceptible and 10 MH-equivocal patients were exposed either to sevoflurane 8 vol% bolus or increasing doses of 2, 4, 6, and 8 vol%. In MH-positive patients, a screening for mutations in the RyR1 gene was performed.
  
  
  RESULTS
  The in vitro parameters initial length, weight, predrug resting tension, and predrug twitch height did not differ between the groups. Sevoflurane caused significant contractures in MH-susceptible but not in MH-nonsusceptible muscle after increasing doses [1.4 (0.3-6.0) vs. 0 (0-0) mN] and after bolus application [6.9 (2.4-21.4) vs. 0 (0-0) mN]. However, only 50% of the susceptible patients developed contractures ≥ 2 mN after increasing concentrations while 83% did so after rapid bolus administration. Presence of an RyR1 mutation was detected in 36% of the examined MH-positive patients but had no influence on developing contractures.
  
  
  CONCLUSIONS
  Sevoflurane-induced contractures do not reliably detect MH susceptibility on an individual level. Therefore, sevoflurane is no suitable alternative for diagnostic use. Mutation-specific effects regarding contracture sizes after incubation with sevoflurane, halothane, or caffeine were not found.
authors: Department of Anaesthesia and Critical Care, University of Wuerzburg, Wuerzburg, Germany.
authors: S
authors: S
authors: Johannsen
authors: W
authors: W
authors: Klingler
authors: D
authors: D
authors: Schneiderbanger
authors: S
authors: S
authors: Heiderich
authors: N
authors: N
authors: Roewer
authors: F
authors: F
authors: Schuster
mesh_terms: D018685:Anesthetics, Inhalation; D001706:Biopsy; D004198:Disease Susceptibility / Q000175:diagnosis*; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006221:Halothane; D006801:Humans; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000175:diagnosis* / Q000235:genetics; D008738:Methyl Ethers; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D011237:Predictive Value of Tests; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D019837:Ryanodine Receptor Calcium Release Channel; D000077149:Sevoflurane; D006221:Halothane