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Malignant Hyperthermia

Background

Malignant hyperthermia (MH) is a life-threatening clinical syndrome of hypermetabolism involving the skeletal muscle. It is triggered in susceptible individuals primarily by the volatile inhalational anesthetic agents and the muscle relaxant succinylcholine, though other drugs have also been implicated as potential triggers.
MH is not an allergy but an inherited disorder that is found both in humans and in swine.

In persons susceptible to MH, the ryanodine receptor in skeletal muscle is abnormal,
and this abnormality interferes with regulation of calcium in the muscle. An abnormal ryanodine receptor that controls calcium release causes a buildup of calcium in skeletal muscle, resulting in a massive metabolic reaction.

This hypermetabolism causes increased carbon dioxide production, metabolic and respiratory acidosis, accelerated oxygen consumption, heat production, activation of the sympathetic nervous system, hyperkalemia, disseminated intravascular coagulation (DIC), and multiple organ dysfunction and failure. Early clinical signs of MH include an increase in end-tidal carbon dioxide (even with increasing minute ventilation), tachycardia, muscle rigidity, tachypnea, and hyperkalemia. Later signs include fever, myoglobinuria, and multiple organ failure.

Anesthetics are inconsistent in triggering MH. A susceptible individual may undergo anesthesia with MH-triggering agents on multiple occasions without incident but may still react to such agents on a subsequent occasion. A history of uneventful anesthesia with MH-triggering agents does not rule out susceptibility to MH. In fact, there are reports of MH episodes occurring even with the use of supposedly safe agents.

More than 30 mutations account for human MH.
Genetic testing is available to establish a diagnosis, but the caffeine halothane contracture test (CHCT) remains the criterion standard. Dantrolene, the antidote, decreases the loss of calcium from the sarcoplasmic reticulum in the skeletal muscle and restores normal metabolism.
Early detection and treatment improve the outcome.

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