Malignant hyperthermia

MH is an autosomal dominant genetic condition characterized by hypermetabolic disorder of skeletal muscle triggered by inhalational anaesthetic agents (except for nitrous oxide) or succinylcholine.

A genetic mutation in the RYR1 ryanodine receptor, which regulates calcium release from the sarcoplasmic reticulum in skeletal muscle cells, causes uncontrolled calcium release into the sarcoplasm, resulting in a hypermetabolic state with increased oxygen consumption, anaerobic metabolism, and muscle activation, leading to cellular ATP depletion, muscle membrane integrity compromise, rhabdomyolysis, and hyperkalemia.

The incidence of MH reactions is estimated at 1 in 10,000-250,000 anesthetic procedures. The prevalence of MH in the US is estimated to range between 1.23-1.91 per 100,000 hospital discharge.

Risk factors for MH include a personal or family history of the condition and the presence of certain genetic mutations. Other factors such as preoperative exercise and pyrexia can also increase the risk of a MH event.

Clinically, MH presents as a hypermetabolic crisis characterized by hyperthermia, muscle rigidity, tachycardia, tachypnea, and evidence of rhabdomyolysis. It may also manifest as an unexplained elevation of ETCO2 and acidosis. Early signs can include inappropriately elevated CO2 production (icnreased ETCO2 on capnography, tachypnea if breathing spontaneously), increased oxygen consumption, mixed metabolic and respiratory acidosis, profuse sweating and mottling of skin, inappropriate increase in HR, cardiac arrhythmias (especially ectopic ventricular beats and ventricular bigeminy), unstable arterial pressure, masseter spasm (if succinylcholine has been used), and generalized muscle rigidity. Later signs can include hyperkalemia, rapid increase in core body temperature, highly elevated blood CK and myoglobin levels, dark urine due to myoglobinuria, severe cardiac arrhythmias and cardiac arrest, and DIC.

The prognosis of MH has significantly improved with early recognition and immediate treatment. The mortality has decreased to < 5% with prompt intervention.