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.[1] 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, [2] 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 multiorgan 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 multiorgan failure. Indications for treatment of malignant hyperthermia (MH) with dantrolene include signs of hypermetabolism, a rapid rise in carbon dioxide in the face of an increase in the minute ventilation, tachycardia, muscle and or jaw rigidity (after succinylcholine), and fever (a late sign). Not all of these indications are present in all patients. If an acute MH reaction appears likely, it is best to start giving dantrolene and other recommended treatment modalities promptly rather than wait too long and have a bad outcome. The longer the wait before initiation of therapy, the lower the likelihood of a complete recovery. If an MH reaction is suspected, referral to a MH muscle biopsy testing center is indicated. A fulminant, rapidly progressive malignant hyperthermia reaction requires early diagnosis and early rapid administration of dantrolene, discontinuance of triggering agents, and assistance from extra personnel. The surgeon should be notified immediately and should stop the procedure as soon as possible (see below). Clinical Presentation Malignant hyperthermia (MH) may occur either in the operating room (OR) or in the early postoperative period. The earliest sign is an increase in end-tidal carbon dioxide. A fulminant reaction is obvious, with very high end-tidal carbon dioxide (> 100 mm Hg), a low pH with a metabolic component, tachycardia and dysrhythmias, rigidity in some cases, rapidly increasing temperature, a mottled skin color, hyperkalemia, myoglobinuria, muscle edema, sympathetic hyperactivity with eventual metabolic exhaustion, increased cellular permeability, whole body edema, disseminated intravascular coagulopathy (DIC), and cardiac and renal failure.