**1. Introduction**

396 Liver Transplantation – Basic Issues

Steininger, R., Roth, E., Fugger, R., Winkler, S., Langle, F., Grunberger, T., Gotzinger, P.,

Therapondos, G., Flapan, A. D., Plevris, J. N. & Hayes, P. C. (2004). Cardiac morbidity and

Tzakis, A., Todo, S. & Starzl, T. E. (1989). Orthotopic liver transplantation with preservation

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Sautner, T. & Muhlbacher, F. (1994). Transhepatic metabolism of TNF-alpha, IL-6, and endotoxin in the early hepatic reperfusion period after human liver transplantation. *Transplantation*, 58, 2, (Jul 27,1994), pp. 179-183,0041-1337 (Print)

mortality related to orthotopic liver transplantation. *Liver Transpl*, 10, 12,

of the inferior vena cava. *Ann Surg*, 210, 5, (Nov,1989), pp. 649-652,0003-4932 (Print)

(1995). Correlation between donor age and the pattern of liver graft recovery after transplantation. *Transplantation*, 60, 8, (Oct 27,1995), pp. 790-794,0041-1337 (Print)

> Malignant hyperthermia (MH) is an inherited, pharmacogenetic disorder of the skeletal muscle, characterized by dangerous hypermetabolic state after anesthesia with succinylcholine and/or volatile halogenated anesthetic agents. MH may also be triggered in susceptible individuals by severe exercise in hot conditions, infections, neuroleptic drugs and overheating in infants1-4.

> 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]-2,4 imidazolidinedione), 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.

> In 1975, Harrison15 described the efficacy of dantrolene in preventing and treating porcine halothane induced-MH. By 1979 the U.S. Food and Drug Administration (FDA) approved dantrolene for use in humans with MH16. The effectiveness of dantrolene in human MH was then confirmed in a multihospital evaluation of dantrolene used to treat anesthetic-induced episodes17. More than four decades after its discovery, dantrolene remains the primary basis for successful MH therapy18.

In the late 1980s, Caffeine Halothane Contracture Test became the gold standard diagnostic test for MH and a variety of neuromuscular disorders associated with MH susceptibility. These disorders include central core disease, Duchenne muscular dystrophy, myotonia congenita, myotonic dystrophy, nonspecific myopathies, and King-Denborough syndrome19.

During liver transplantation, some commonly employed anesthetic agents may trigger MH in susceptible patients. This occurrence, in such a complex scenario and with such delicate patients, can make anesthesia management even more challenging. Besides this, dantrolene is hepatotoxic, which can pose another injury risk to the graft20.
