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Malignant hyperthermia (MH) is a rare and potentially life-threatening disorder of skeletal muscle metabolism that is typically triggered by halogenated volatile anesthetics and depolarizing muscle relaxants in susceptible patients. In rare cases, MH is triggered by strenuous factors, such as extreme heat or other exercise. Since MH can occur rapidly and with fatal consequences, it is essential that all staff—particularly anesthesiologists—in facilities that administer MH-triggering anesthesia is sufficiently trained to treat susceptible patients.

Clinical studies have found halothane to be the most potent MH trigger, though the onset can be exacerbated by the addition of succinylcholine. In MH-susceptible patients, the trigger agents accelerate the metabolic state, impeding the body’s ability to regulate body temperature and blood oxygen levels. The characteristic symptoms of MH are hypercapnia, acidosis, muscle rigidity, cardiac arrhythmia, and fever. Most MH events occur shortly after general anesthesia is administered, but the one-hour period following surgery is also considered a critical time. Thus, MH-susceptible patients should be monitored carefully in both the operating room and the postanesthesia care unit (PACU).

This inherited disorder is autosomal dominant, and while prevalence is estimated to be at 1:3000, from 2000 to 2005, the number of cases in the United States has risen from 372 to 521 per year. The potentially fatal outcome of MH, its quick progression, rising numbers of cases, and difficulty in its diagnosis highlight the importance of identifying at-risk patients and taking sufficient precautions before administering general anesthesia.


MH is triggered by the hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum. Traditional research indicates that MH is caused by a defect in calcium release by the ryanodine receptor 1 (RYR-1) in the sarcoplasmic reticulum, which is a crucial step in muscle contraction. When the susceptible patient is exposed to trigger agents, excessive calcium is released by the RYR, causing sustained skeletal muscle contraction and ultimately, rigidity. However, recent findings show an RYR mutation is not necessary for MH to occur. Other mechanisms by which excess amounts of calcium enters the cell through nonspecific cation channels can cause an MH attack.

Halothane has been identified as triggering a statistically significant faster onset of MH than other agents, followed by isoflurane, according to the time interval between anesthesia administration and development of clinical symptoms. The median onset time of MH due to halothane is 20 minutes compared to that of isoflurane (30 minutes). However, since halothane is no longer used in western countries, it is essential to be aware of all of MH’s triggering agents.

The Malignant Hyperthermia Association of the United States (MHAUS) has identified the following as unsafe for use on susceptible patients: inhaled general anesthetics (desflurane, enflurane, ether, halothane, isoflurane, methoxyflurane, sevoflurane) and succinylcholine.

The effect of succinylcholine, which is used to cause a rapidly onset but short-lived paralysis, on triggering MH is controversial. ...

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