Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, high fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible are generally otherwise normal when not exposed.
The cause of MH is the use of certain volatile anesthetic agents or succinylcholine in those who are susceptible. Susceptibility can occur due to at least six genetic mutations, with the most common one being of the RYR1 gene. These genetic variations are often inherited from a person's parents in an autosomal dominant manner. The condition may also occur as a new mutation or be associated with a number of inherited muscle diseases, such as central core disease.
In susceptible individuals, the medications induce the release of stored calcium ions within muscle cells. The resulting increase in calcium concentrations within the cells cause the muscle fibers to contract. This generates excessive heat and results in metabolic acidosis. Diagnosis is based on symptoms in the appropriate situation. Family members may be tested to see if they are susceptible by muscle biopsy or genetic testing.
Treatment is with dantrolene and rapid cooling along with other supportive measures. The avoidance of potential triggers is recommended in susceptible people. The condition affects one in 5,000 to 50,000 cases where people are given anesthetic gases. Males are more often affected than females. The risk of death with proper treatment is about 5% while without it is around 75%. While cases that appear similar to MH have been documented since the early 20th century, the condition was only formally recognized in 1960.
Malignant hyperthermia is inherited as a dominant gene in pigs and in humans. It is characterized by a rapidly increasing body temperature up to 118oF with a metabolic rate over 10x normal, an intense peripheral vasoconstriction with blood pressures over 400 mmHg and a fatal outcome in most cases. The MH syndrome is triggered by exercise, hauling to market, breeding activity, hot weather and other stress factors. In humans, the cases are triggered by depolarizing muscle relaxants, halothane anesthesia and other halogenated anesthesia compounds. Non-depolarizing muscle relaxants such as pancuronium and vecuronium are safer to use. Organon 9426 (rocuronium) is safe to use and provides carry over protection against the development of MH. The widespread use of sevoflurane in humans has reduced the incidence of MH to 1:550,000. Only two cases of MH have been reported in the USA during the past 30 years. The MH susceptible pig is an outstanding animal model for research purposes and has enabled the development of new muscle relaxants and anesthesia agents that are safer for human use. The sodium channels in MH susceptible animals are leaky and allow the influx of sodium into muscle cells which must be pumped out by sodium-potassium ATPase, thereby using ATP and generating heat.
Microbiology: Current Research