Malignant hyperthermia (MH) is a clinical syndrome characterized by uncontrolled skeletal muscle metabolism. First defined in 1960 by Denborough and Lovell, it is classically “triggered” by volatile anesthetics and the depolarizing muscle relaxant succinylcholine in genetically susceptible individuals. MH is caused by uncontrolled calcium release in skeletal muscle cells as a result of abnormal function of the ryanodine receptor (RYR1). Diagnosis can be made clinically, by caffeine-halothane contracture testing of a muscle biopsy specimen, or by genetic testing. The caffeine-halothane test is very sensitive. However, it is invasive and expensive (about $800). Genetic testing for one of several known mutations of the RYR-1 genes is done via a simple blood test. Although it is not very sensitive, it is very specific and much less costly (about $200).

The overall incidence of MH-susceptible patients in the general population is hard to estimate, because it is a “cluster” disease. However, in 2005, there were 12 confirmed cases and an additional 10 probable cases in the United States, according to an official at the Malignant Hyperthermia Association of the United States (MHAUS).

MH can occur at any time during anesthesia or in the immediate postoperative period. It is the standard of care to ask every patient exposed to a triggering agent if he or she has a family history suspicious for MH (“Has a family member ever had a dangerous or unusual reaction to anesthesia? etc.”). Although it is a rare disease, it is an important one in terms of anesthetic practice—anesthesiologists are expected from a medical/legal standpoint to be able to recognize and treat MH even if they are seeing it for the first time.

The most consistent indicator of potential MH is a large increase in end-tidal carbon dioxide. End tidal CO₂ can double or triple in minutes (although it may increase over hours). Masseter rigidity is another early sign, and tachycardia, arrhythmias, unstable or rising blood pressure, cyanosis and mottling, myoglobinuria, and tachypnea follow. Whole-body rigidity is a specific sign of MH and is seen in the limbs, abdomen, and chest if muscle relaxants have not been used. Respiratory and metabolic acidosis indicate fulminant MH and are typically followed by temperature elevation, a late sign. The temperature rise can be rapid and may exceed 43°C. Rhabdomyolysis
and disseminated intravascular coagulation (DIC) may also occur. Death is usually from cardiac arrest secondary to acidosis or hyperkalemia. In the dantrolene era, mortality from MH is less than 10%.