Malignant Hyperthermia

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 calcium (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, resulting in respiratory and metabolic acidosis. In response to the acidosis, patients breathing spontaneously develop tachypnea that only partially compensates.

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. Hypercapnia (detected by increased end-tidal carbon dioxide [CO2]) may be an early sign. 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.

• 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 minutes to, occasionally, several hours after inhalational anesthesia is begun (1). Early diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea, tachycardia, and increased end-tidal CO2.

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

• Rapid cooling and supportive measures

It is critical to cool patients with malignant hyperthermia as quickly and effectively as possible (see Heatstroke: Treatment) to prevent damage to the central nervous system 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 disseminated intravascular coagulationAirway Establishment and Control/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.