Malignant Hyperthermia

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In a susceptible person, exposure to a triggering anaesthetic causes excessive calcium release from the sarcoplasmic reticulum through the type 1 ryanodine receptor, RyR1. This is like a calcium gate that becomes stuck open: muscle fibres remain contracted, ATP is rapidly consumed, and aerobic and anaerobic metabolism accelerate. The resulting acidosis, carbon dioxide production, heat generation, hyperkalaemia, and rhabdomyolysis form a hypermetabolic crisis—not a primary fever. Susceptibility is inherited in an autosomal dominant pattern with incomplete penetrance. Pathogenic variants in RYR1 account for approximately 60–70% of identified cases; CACNA1S accounts for about 1%, and STAC3 for less than 1%. Up to 40% of susceptible people have no causative variant identified by current testing. A person with an MH-susceptibility variant has a 50% chance of passing that variant to each child, but inheritance of the variant does not predict that every exposure will produce a clinically obvious crisis. Previous uneventful anaesthesia therefore does not rule out susceptibility. The triggers are all potent halogenated volatile inhalational anaesthetics—halothane, enflurane, isoflurane, sevoflurane, desflurane, and...