Comparison of European and North American Malignant Hyperthermia diagnostic protocol outcomes for use in genetic studies

Abstract

Background: Halothane and caffeine diagnostic protocols and an experimental ryanodine test from the North American Malignant Hyperthermia (MH) Group (NAMHG) and the European MH Group (EMHG) have not been compared in the same persons until now. Methods: The outcomes of the NAMHG and EMHG halothane and caffeine contracture tests were compared in 84 persons referred for diagnostic testing. In addition, the authors assessed the experimental ryanodine protocol in 50 of these persons. Results: Although the NAMHG and EMHG halothane protocols are slightly different methodologically, each yielded outcomes in close (84-100%) agreement with diagnoses made by the other protocol. Excluding 23 persons judged to be equivocal (marginally positive responders) by the EMHG protocol resulted in fewer persons classified as normal and MH susceptible (42 and 19, respectively) than those classified by the NAMHG protocol (48 and 34, respectively). For the 61 persons not excluded as equivocal, the diagnoses were identical by both protocols, with the exception of one person who was diagnosed as MIt susceptible by the NAMHG protocol and as 'normal' by the EMHG protocol. The NAMHG protocol produced only two equivocal diagnoses. Therefore, a normal or MH diagnosis by the NAMHG protocol was frequently associated with an equivocal diagnosis by the EMHG protocol. The time to 0.2-g contracture after the addition of 1 μM ryanodine completely separated populations, which was in agreement with the EMHG protocol and, except for one person, with the NAMHG protocol. Conclusions: Overall, the NAMHG and EMHG protocols and the experimental ryanodine test yielded similar diagnoses. The EMHG protocol reduced the number of marginal responders in the final analysis, which may make the remaining diagnoses slightly more accurate for use in genetic studies.