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Abstract - 72 - SUM MAR Y Since its recognition (Denborough and Lovell, 1960), malignant hyperthermia (Mil) has aroused great interest among anaesthetists. It can occur in genetically predisposed human patients on administration of inhalational general anaesthetics; either alone or in combination with muscle relaxants~ The report in 1966 by Hall et al. of MH indued by halothane and succinylcholine in a stress-susceptible strain of swine, provided an animal model of the human disease . The incidence of MH ia one in 15,000 anesthetic children and one in 50,000 anesthetic adults (Hritt, 1972). Males and females are af~ected equally in children but there is a preponderance of males in adulthood (Gritt et al., 1977; Ellis and Halsall, 1980). Susceptibility to MH appears to be inherited in an autosoma~. dominant fashion, with .incomplete penetrance and variable expressivity (Britt et al.,1969). Occasionally, these patients will have mild subclinical weakness, mild creatine phosphokinase (CPK) elevation, - 73- and nonspecific changes on muscle biopsy (lsaace and Larlow, 1970; Harriman et al., 1973). In general,Mti has not been associated with well-defined neuromuscular disorders (Engel, 1977). However, Watters et al • (1977) reported three children with Duchenne musclar dystrophy in whom muscle breakdown waa enhanced by general anesthesia with halothane and succinylcholine. There have also been a number of reports of t1H assoc ia ted wit h my otonia dys trophi ca myotonia congenita and central core disease (Kaufman, 1960; Saidman et al. 1)64; Cody, 1968; Ravin et al. 1975; Engel, 1977, Mitchell et al. 1978). The syndrome of MH developing during anathesia is marked by tachycardia, arrhythmia, tachypnea, unstable blood pressure, cyanosis, skin mottling and rigidity (Gronert, 1980). Elevated temperature, a result of the underlying biochemical deragnement, occurs as the syndrome evolves (Britt, 1979a). The temperature may soar, rising at a rate of 1 degree every five minutes, to as high as 43°C. There is hypercarbia, acidemia, hyperkalemia and massive elevation of CPK. Early hy~ercalcemia may be followed by late hypocalcemia (Britt, 1979a). Myoglobinuria and resulting renal failure are serious - 74 - complications of Mli. The mortality rate is 64 percent (urIt t and Kalow, 1970a). The disorder can be triggered by any potent volatile agent, ketamine and depolarizing relaxants. Uee of succinylcholine is often associated with an abrupt onset of MH (i3ritt, 1979a; Gronert, 1980 ). Excessively elevated myoplamsic calcium can centration causes the acute catabolic liH crisis (Btitt, 1979a). Heat-generating mechanisms initiated by hypercalcemia include breakdown of glycogen, uncoupling of oxidative phosphorylation , and accelerated hydrolysis of ATP by myosin ATPase (Britt, 1979a). High myoplamic calcium also produces muscle contracture. The defect that underlies the abnormal regulation of intracellular calcium is not known. A fragile sercolemmal membrane, allowing calcium influx, defective mitochondria, or sarcoplasmic reticulum that is unable to pump calcium may all be involved (Engel, 1977; Britt, 1979a; Gronert, 1980 ) As soon as the diagnosis is suspected, all anesthesia should be discontinued.Patients with the fulil -til own ”syndromerequire prompt treatmentwith hyperventillationwith 100 percent oxygen, biocarbonate, cooling, and known specific therapeutic diuretics. Dantrolene is the only agent. lt should be given as soon 8~ -75 - the diognosis is made.The recommended dose is 1 to 2 mg per Kilogram 1VJ which may be repeated every 5 to 10 minutes, to a total dose of 10 mg per kilogram. The drug should be continued orall¥ for 24 hours following control .Vigilance over the patient’s clinical state and laboratory values is required for several days after the attack , as later renal and hematologic complications may occur (critt and Kalow, 1970a; Faust et aI, 1979~ Gronert, 1980 and Waterman, 1981). • Screening of relatives of affected patients for susceptibility to MH is important. Seventy percent of the cases at risk have increased serum CPK activities (Britt et al. 1976). Without this finding, in vitro testing of muscle strips for an abnormal contracture response to halothane, caffeine or a combination of both agents can be done (~alow et al. ,1977; Ellis et al., 1978c; ~rding ) E 11is et a!’ (1978b) have indicated that et a L, , 1984 • the fluoride-resistant gene for plasma cholinesterase has an increased frequency in relatives of patients who had experienced MH. The findings of Willner et al.(1980) that the phosphorylase ratio in muscle from susceptible patients was elevated held promise of such a test , in part because needle biopsy could supply the specimen. - 76 - A relatively non-invasive screening technique using venous blood analyzed by high performance liquid chromatography (1IPLC) was developed to assess the effects of halothane on platelet nucleotide metabolism. The platelet- halothane bioassay (PHS) is highly reproducible and specific for detecting MH with a significant degree of expression at the time of the venipuncture (Solomons and Masson, 1984) Pretreatment with Dantrolene p.o.the day before surgery (4 to 7mq per kg., individed doses), avoidaDce of premedication with phenothiazines or atropine, use of safe anesthetic agents such as nitrous oXide, thiopental and opiates, and csreful perioperative monitoring will prevent the MH syndrome (Gronert, 1980). |