Malignant hyperthermia of anesthesia

Malignant hyperthermia (MH), also known as malignant hyperthermia of anesthesia or malignant hyperpyrexia, is a potentially life-threatening pharmacogenetic disorder of skeletal muscle. It is triggered by exposure to certain volatile anesthetic agents (such as halothane, sevoflurane, desflurane, and isoflurane) and/or the depolarizing muscle relaxant succinylcholine. The condition results from uncontrolled calcium release from the sarcoplasmic reticulum in skeletal muscle cells, leading to sustained muscle contraction, a hypermetabolic state, and rapidly rising body temperature. The hallmark clinical features of a malignant hyperthermia crisis include a rapid and unexplained rise in end-tidal carbon dioxide (hypercapnia), skeletal muscle rigidity (particularly masseter muscle rigidity or generalized rigidity), tachycardia, metabolic acidosis, rhabdomyolysis, hyperkalemia, and a dramatic increase in core body temperature that can exceed 40°C (104°F). If untreated, MH can progress to disseminated intravascular coagulation, multi-organ failure, and death. The condition primarily affects the skeletal muscle system but secondarily impacts the cardiovascular, renal, and central nervous systems due to the systemic metabolic crisis. Most cases of MH susceptibility are caused by pathogenic variants in the RYR1 gene, which encodes the ryanodine receptor type 1, the primary calcium release channel in skeletal muscle. Less commonly, variants in the CACNA1S gene (encoding the alpha-1S subunit of the dihydropyridine receptor) are implicated. Individuals who carry these variants are typically asymptomatic between episodes and may have no prior history of adverse anesthetic reactions. Diagnosis of susceptibility can be confirmed through the caffeine-halothane contracture test (CHCT) performed on a muscle biopsy specimen, or increasingly through genetic testing. The specific and effective treatment for an acute MH crisis is the intravenous administration of dantrolene sodium, which acts by inhibiting calcium release from the sarcoplasmic reticulum. Supportive measures include active cooling, correction of metabolic acidosis and hyperkalemia, and monitoring for complications. Prevention in known susceptible individuals involves the use of non-triggering anesthetic agents and avoidance of succinylcholine.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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