An update on the malignant hyperthermia syndrome.
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In humans, MH is inherited in an autosomal dominant fashion; in swine, the principal model for MH, it is in a recessive fashion. Those with MH susceptibility usually are asymptomatic except in the presence of certain "triggering" anaesthetic agents such as isoflurane, enflurane and the muscle relaxant succinylcholine. Upon such exposure hypermetabolism, increased CO2 production, acidosis, muscle rigidity, rhabdomyolysis and hyperthermia occur. Untreated, death may result in 70% of patients. With prompt diagnosis and treatment with dantrolene sodium, the mortality is less than 10%. The overall incidence of MH is low (perhaps 1:50,000 anaesthetics), but it is more common in children. Children also display a paradoxical increase in jaw muscle tone to succinylcholine which often presages MH, but confusing clinically, may also be a normal response to succinylcholine. The pathophysiology of MH centres around a defect in calcium flux in skeletal muscle. A specific base pair change in the gene that codes for the ryanodine receptor calcium channel in muscle has been demonstrated in susceptible swine, but occurs rarely in humans. It is hoped that the understanding of the molecular genetics of MH will lead to a simpler diagnostic test than is currently available, and enhance our understanding of MH and its relation to other myopathies.
Rosenberg
H
H
Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192, USA.
Fletcher
J E
JE
D000777:Anesthetics / Q000009:adverse effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics; D002648:Child; D003620:Dantrolene / Q000627:therapeutic use; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D008305:Malignant Hyperthermia / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D013390:Succinylcholine / Q000009:adverse effects; D013552:Swine
D000777:Anesthetics; D015220:Calcium Channels; D003620:Dantrolene; D013390:Succinylcholine; D002118:Calcium