An MH crisis played in a German TV show
Malignant Hyperthermia (MH)
Susceptibility to malignant hyperthermia susceptibility (MHS) is an autosomal dominant predisposition of clinically inconspicuous individuals to respond abnormally when exposed to volatile anesthetics, depolarizing muscle relaxants or extreme physical activity in hot environments. During exposure to triggering agents, a pathologically high increase in myoplasmic calcium concentration leads to increased muscle metabolism and heat production resulting in muscle contractures, hyperthermia associated with metabolic acidosis, hyperkalemia, and hypoxia. The metabolic alterations usually progress rapidly and without immediate treatment, up to 70% of the patients die. Early administration of dantrolene, an inhibitor of calcium release from the sarcoplasmic reticulum (SR) has successfully aborted numerous fulminant crises and has reduced the mortality rate to less than 10%.
The triggering substances elicit an event only in a fraction of anesthesias. In accordance with the varying severity of the clinical picture, non-anesthetic MH-like episodes triggered by overheating, body exertion, and infections have been described. MH-like crises have also been observed in patients with myopathies such as myotonia fluctuans, Duchenne/Becker progressive mucular dystrophy, myotonia congenita and myotonic dystrophy. It seems very likely that the molecular mechanisms underlying these MH-like events differ from those of true MH susceptibility, e.g. in the myotonic diseases as increased myotonic reactions to anesthetic agents. This different pathogenesis, of course, does not obviate the need for caution when considering general anesthesia in these disorders.
In up to 70% of MHS families, variants in the skeletal muscle isoform of the ryanodine receptor gene RYR1 have been identified. In contrast to the CCD mutations, most of the MHS variants are situated at the N-terminus of the protein.