MALIGNANT HYPERTHERMIA IN CRITICALLY ILL PATIENTS

Abstract

Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain agents, either conventional such as depolarizing muscle relaxant (specifically, succinylcholine) or even volatile anesthetics (e.g. isoflurane), and also can be triggered by certain newly discovered drugs including (serotonergic drugs, phosphodiesterase type III inhibitors, statins, ondansteron, methylene blue, tetracaine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. MH may occur in the early postoperative period and can recur in the intensive care unit in following 24 to 48 hours. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high. Malignant hyperthermia in critically patients Summar y - 26 - A clinical grading scale helps determine if a malignant hyperthermia (MH) episode has occurred. Contracture testing, the standard diagnostic test for MH since the mid-1970s, relies on the in vitro measurement of contracture response of biopsied muscle to graded concentrations of caffeine, halothane, and other calcium-releasing agents. To date, two genes predisposing to MHS have been identified; four additional loci have been mapped, but the genes have not been identified. MHS1 is associated with mutations in RYR1, encoding ryanodine receptor type 1; MHS5 is associated with mutations inCACNA1S, encoding a skeletal muscle calcium channel. Up to 70% of MHS is caused by mutations in RYR1 and about 1% results from mutations in CACNA1S. Early diagnosis of MHS is essential for better prognosis and lower mortality and morbidity. Successful treatment of an acute episode of MH includes discontinuation of the triggering agents (e.g. succinylcholine); administration of dantrolene sodium intravenously; surface and intravenous and body cavity cooling with cold solutions for hyperthermic individuals; and treatment of metabolic abnormalities. Affected individuals who display extreme hyperthermia are at risk for disseminated intravascular coagulation; therefore, a coagulation profile should be obtained on all individuals experiencing fulminant MH. Prevention of primary manifestations: Avoidance of triggering agents (e.g. succinylcholine, volatile anesthetics as isoflurane)). Concerning to the other drugs recently discovered to be implicated as triggers of MH including (serotonergic drugs, phosphodiesterase type III inhibitors, Malignant hyperthermia in critically patients Summar y - 26 - statins, ondansteron, methylene blue, tetracaine), There is no convincing evidence to support the restriction of these drugs in MH-susceptible patients. Malignant hyperthermia susceptibility (MHS) is inherited in an autosomal dominant manner. Most individuals diagnosed with MHS have a parent with MHS; however, the parent may not have experienced an episode of MH. The proportion of individuals with MHS caused by de novo mutations is unknown. Each child of an individual with MHS has a 50% chance of inheriting the disease-causing mutation.