Malignant hyperthemia

SummaryMalignant hyperthermia (MH) was first recognised as a potentially fatal pharmacogenetic disorder nearly 50 years ago. The abnormality has been localised to skeletal muscle, specifically the mechanisms regulating myoplasmic calcium ion homeostasis. The gene principally implicated is RYR1, which encodes the skeletal muscle sarcoplasmic reticulum calcium release channel, but the genetics of MH are relatively complex, with more than 100 mutations described in RYR1 and with a significant minority of cases not involving this gene. This review describes how the pathophysiology of MH relates to the clinical features, which follow a logical pattern. Reasons for the reaction reaching an untreatable stage are proposed, emphasising the importance of early diagnosis and aggressive treatment using the latest guidelines. Early intervention in suspected cases, and the lack of specificity of any single clinical feature for MH, necessitates laboratory confirmation of the diagnosis using muscle biopsy specimens. These relatively invasive tests can also be used to screen family members of known cases, although the limited introduction of DNA testing has obviated the need for some individuals to have a muscle biopsy. Patients at risk of developing MH can receive general anaesthesia and guidelines for this are described.