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 Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more and myoglobinuria have occurred.

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 Key Points 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,... read more ). 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 electrocardiogram, blood tests (complete blood count with platelets, electrolytes, blood urea nitrogen, creatinine, creatine kinase, calcium, prothrombin time, partial thromboplastin time, fibrinogen, D-dimer), and urine testing for myoglobinuria.

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.

It is critical to cool patients with malignant hyperthermia as quickly and effectively as possible (see Heatstroke: Treatment Treatment Heatstroke is hyperthermia accompanied by a systemic inflammatory response causing multiple organ dysfunction that may result in death. Symptoms include temperature > 40° C and altered mental... read more ) 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 Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more , severe hyperthermia, and disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more . Dantrolene 2.5 mg/kg IV every 5 minutes as needed, up to a total dose of 10 mg/kg should be given in addition to the usual physical cooling measures. The dose of dantrolene is titrated based on heart rate and end-tidal CO2. In some patients, tracheal intubation (see Airway Establishment and Control/Tracheal Intubation Tracheal Intubation Most patients requiring an artificial airway can be managed with tracheal intubation, which can be Orotracheal (tube inserted through the mouth) Nasotracheal (tube inserted through the nose)... read more ) 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.

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 and those with a strong family history. Dantrolene should be available at the bedside.