Malignant Hyperthermia in Liver Transplantation

MH produces rapid increase in body temperature (by as much as 1oC in five minutes) and extreme acidosis. These are a result of acute loss of control of intracellular calcium levels and compensatory uncontrolled increases in skeletal muscle metabolism, which may progress to severe rhabdomyolysis. Critical worldwide attention to MH began in 1960 with the reports of Denborough and Lovell. They described MH in a young man who had a history of several deaths of relatives during anesthesia. He developed tachycardia, hot and sweaty skin, peripheral mottling and cyanosis during general anesthesia using halothane. After prompt symptomatic treatment, the episode was aborted5-6. The term malignant hyperthermia was first quoted by Wilson and colleagues in 19677. In this same year, Dantrolene Sodium, a hydantoin derivative (1-[5-(4-nitrophenyl)-2-furanyl]methylene]imino]-2,4imidazolidinedione), was first used because of its possible muscle-relaxing properties8. Shortly thereafter, dantrolene was shown to alleviate muscle spasticity effectively in animals9 and humans10. Later, it was shown that dantrolene uncoupled the excitationcontraction process during skeletal muscle stimulation11. A few years later, an association between MH and porcine stress syndrome was proposed, providing an animal model for MH12-13. Because malignant hyperthermia was thought to result from continuous muscle contraction, perhaps through an abnormality in the excitation-contraction coupling mechanism, the compound was tested as a treatment for this condition14.