Malignant hyperthermia is a life-threatening elevation in body temperature usually resulting from a hypermetabolic response to concurrent use of a depolarizing muscle relaxant and a potent, volatile inhalational general anesthetic. Manifestations can include muscle rigidity, hyperthermia, tachycardia, tachypnea, rhabdomyolysis, and respiratory and metabolic acidosis. Diagnosis is clinical; patients at risk can be tested for their susceptibility. The highest priority treatments are rapid cooling and aggressive supportive measures.

The muscle relaxant involved is usually succinylcholineSome Trade Names
ANECTINE
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; the inhalational anesthetic is most often halothane, but other anesthetics (eg, isoflurane, sevoflurane, desflurane) may also be involved. This drug combination causes a similar reaction in some patients with muscular dystrophy and myotonia.

Pathophysiology

Malignant hyperthermia affects about 1/20,000 people. Susceptibility is inherited, with autosomal dominant inheritance and variable penetrance. Most often, the causative mutation affects the ryanodine receptor of skeletal muscle; however, > 22 other causative mutations have been identified.

The mechanism may involve anesthetic-induced potentiation of Ca exit from the sarcoplasmic reticulum of skeletal muscle in susceptible patients. As a result, Ca-induced biochemical reactions are accelerated, causing severe muscle contractions and elevation of the metabolic rate.

Complications: Hyperkalemia, respiratory and metabolic acidosis, hypocalcemia, and rhabdomyolysis with CK elevation and myoglobinemia may occur, as may coagulation abnormalities (particularly disseminated intravascular coagulation [DIC]). In older patients and patients with comorbidities, DIC may increase the risk of death.

Symptoms and Signs

Malignant hyperthermia may develop during anesthesia or the early postoperative period. Clinical presentation varies, depending on the drugs used and the patient's susceptibility. Muscular rigidity, especially in the jaw, is often the first sign, followed by tachycardia, other arrhythmias, tachypnea, acidosis, shock, and hyperthermia. Temperature is usually ≥ 40° C and may be extremely high (ie, > 43° C). Urine may appear brown or bloody if rhabdomyolysis and myoglobinuria have occurred.

Diagnosis

• Clinical evaluation
• Testing for complications
• Susceptibility testing for people at risk

The diagnosis is suspected by the appearance of typical symptoms and signs within 10 min to, occasionally, several hours after inhalational anesthesia is begun. Early diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea, tachycardia, and increased end-tidal CO₂.

There are no immediately confirmatory tests, but patients should have testing for complications, including ECG, blood tests (CBC with platelets, electrolytes, BUN, creatinine, CK, Ca, PT, PTT, fibrinogen, d-dimer), and urine testing for myoglobinuria.

Other diagnoses must be excluded. Perioperative sepsis may cause hyperthermia but rarely as soon after induction. Inadequate anesthesia can cause increased muscle tone and tachycardia but not elevated temperature. Thyroid storm and pheochromocytoma rarely manifest immediately after anesthetic induction.

Susceptibility testing: Testing for susceptibility to malignant hyperthermia is recommended for people at risk based on a family history of the disorder or a personal history of a severe or incompletely characterized previous adverse reaction to general anesthesia. The caffeine halothane contracture test (CHCT) is the most accurate. It measures the response of a muscle tissue sample to caffeine and halothane. This test can be done only at certain referral centers and requires excision of about 2 g of muscle tissue. Genetic testing has limited sensitivity (about 30%) but is quite specific; patients in whom a mutation is identified do not require the CHCT.

Treatment

• Rapid cooling and supportive measures
• DantroleneSome Trade Names
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It is critical to cool patients as quickly and effectively as possible (see Heat Illness: Treatment) to prevent damage to the CNS and also to give patients supportive treatment to correct metabolic abnormalities. Outcome is best when treatment begins before muscular rigidity becomes generalized and before development of rhabdomyolysis, severe hyperthermia, and DIC. DantroleneSome Trade Names
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(2.5 mg/kg IV q 5 min as needed, up to a total dose of 10 mg/kg) should be given in addition to the usual physical cooling measures. In some patients, tracheal intubation, paralysis, and induced coma are required to control symptoms and provide support. Benzodiazepines given IV, often in high doses, can be used to control agitation. Malignant hyperthermia has a high mortality and may not respond to even early and aggressive therapy.

Prevention

Local or regional anesthesia is preferred to general anesthesia when possible. Potent inhalational anesthetics and depolarizing muscular relaxants should be avoided in patients who are susceptible. Nondepolarizing muscular blockers are the preferred preanesthetic drugs. Preferred anesthetics include barbiturates (eg, thiopentalSome Trade Names
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), etomidateSome Trade Names
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, and propofolSome Trade Names
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. DantroleneSome Trade Names
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should be available at the bedside.

Last full review/revision February 2010 by James P. Knochel, MD

Content last modified February 2012