title: Muscular body build and male sex are independently associated with malignant hyperthermia susceptibility.
abstract: OBJECTIVE
  Malignant hyperthermia susceptibility (MHS) is a disorder of the regulation of calcium in skeletal muscle. Muscular individuals have been shown to have a 13.6-fold increased risk of death during malignant hyperthermia (MH) episodes and are more likely to experience a recurrence after initial treatment. Twenty-five percent of severe MH episodes have occurred in elite athletes. This study investigated the association between MHS and muscular body build.
  
  
  METHODS
  Data were obtained from existing reports in the North American Malignant Hyperthermia Registry, including the Report of Muscle Biopsy and Contracture Testing (caffeine-halothane contracture test [CHCT]) as well as Adverse Metabolic or Muscular Reaction to Anesthesia (AMRA) reports. Malignant hyperthermia susceptible individuals were compared with MH negative individuals with regard to body build and reason for testing. Males were also compared with females. Both the CHCT and the AMRA forms were reviewed for comments.
  
  
  RESULTS
  Of the 1,292 individuals diagnosed with MHS by CHCT, males were more likely to be diagnosed with the disorder than females (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.99 to 2.7; P < 0.001). Muscular individuals were more likely to be diagnosed with MHS than non-muscular individuals (OR, 1.94; 95% CI, 1.51 to 2.49; P < 0.001). Males were more likely to be tested after having a possible MH episode (OR, 2.33; 95% CI, 1.45 to 2.1; P < 0.001). Logistic regression showed that male sex (OR, 2.28; 95% CI, 1.93 to 2.7; P < 0.001) and muscular body build (OR, 2.17; 95% CI, 1.21 to 3.9; P = 0.01) were independently predictive of MHS. The interaction between muscular body build and male sex was not significant (P = 0.13). Indications for testing, MH episode vs family history of MH, did not differ between muscular and non-muscular individuals (P = 0.44). Eight of 839 AMRAs and two reports of CHCT had comments describing athletic abilities. Ryanodine receptor type 1 (RYR1) gene mutations were found in five of these athletes.
  
  
  CONCLUSIONS
  Muscular body build and male sex are strongly associated with MHS.
authors.affiliation: Allegheny Health Network, Department of Anesthesiology, Allegheny General Hospital, 302 E North Ave, Pittsburgh, PA, 15212, USA. brian.butala@ahn.org.
authors.forename: Brian
authors.initials: B
authors.lastname: Butala
authors.affiliation: North American Malignant Hyperthermia Registry of MHAUS, UPMC Mercy Hospital, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brandom
mesh_terms: D000328:Adult; D000758:Anesthesia / Q000009:adverse effects; D056352:Athletes / Q000706:statistics & numerical data; D001823:Body Composition / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000453:epidemiology* / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000502:physiology*; D012042:Registries; D012737:Sex Factors; D055815:Young Adult