Description

Malignant hyperthermia (IM) is a pharmacogenetic disease of skeletal muscles, which is characterized by a hypermetabolic response to powerful volatile anesthetic gases such as halothane, sevoflurane, desflurane and succinylcholine, a depolarizing muscle relaxant. Seldom in humans occurs after physical stress secondary to excessive exercise or heat. In IM the incidence of reactions in IM varies between 1 / 5,000 to 1 / 50,000-100,000 anesthesia. However, the prevalence of genetic abnormalities can affect 1 every 3,000 individuals. IM affects men, some breeds of pigs, dogs, horses and probably other animals as well. The earliest specific diagnostic sign is the increase in exhaled carbon dioxide. Typical signs of MI include marked hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle stiffness and rhabdomyolysis; all these signs are linked to a hypermetabolic response. In the human species, this syndrome is inherited as an autosomal dominant trait. The pathophysiological changes of IM are due to an uncontrolled increase in myoplasmic calcium, which triggers biochemical processes linked to muscle activation. Following the depletion of ATP, the integrity of the muscular membrane, which produces hyperkalemia and rhabdomyolysis, is compromised. In many cases, the syndrome is due to a ryanodine receptor defect. Over 90 mutations have been identified in the RYR-1 gene (located on chromosome 19q13.1) and at least 25 are responsible for IM. Diagnostic tests are based on in vitro detection of muscle contraction on biopsies in response to halothane, caffeine and other substances. The identification of genetic mutations has allowed the introduction, limited so far, of genetic tests that identify the susceptibility to IM. In view of the increased sensitivity of genetic testing, molecular genetics will be of great help in identifying mutations at risk. Sodium dantrolene is a specific antagonist of pathophysiological changes in IM and should be administered at the time of anesthesia. The syndrome is probably fatal if left untreated, but thanks to the great progress in understanding the clinical symptoms and the pathophysiology of the syndrome, IM mortality dropped from 80% of thirty years ago to 5% today.

External Information

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