A preventable disaster
In 1960, the medical journal The Lancet published a sobering report of a 21-year-old student whose broken leg required surgical repair but who was less concerned about his leg than the risk of general anesthesia. He told his doctor that, since 1922, 10 of his relatives had died as a direct result of inhaled anesthesia. The young man ended up having surgery on his leg and surviving an episode of what would later be called “malignant hyperthermia” (MH), a reaction to certain anesthetics that leads to uncontrolled muscle contractions, accelerated metabolism, high fever, and all too often, if not treated, death.
The 1960 report markedly increased awareness of the phenomenon, which, even as late at 1976, still carried an estimated mortality rate of 28 percent.
The disastrous phenomenon appears to be caused by uncontrolled leakage of calcium from inside muscle fibers. It’s particularly common among people with central core disease, although it also occurs in people who don’t have CCD.
According to the Malignant Hyperthermia Association of the United States, the inhalation anesthetics that can trigger MH include sevoflurane, desflurane, isoflurane, halothane, enflurane and methoxyflurane. In addition, the muscle relaxant known as succinylcholine (brand name Anectine), a “depolarizing” relaxant often used with anesthesia, can also trigger the response.
MHAUS lists as safe for people with MH susceptibility (MHS) all local anesthetics, as well as the anesthetics and pain relievers nitrous oxide, barbiturates, narcotics, propofol, benzodiazepines, ketamine and etomidate. It lists the “nondepolarizing” muscle relaxants pancuronium, cisatracurium, atracurium, mivacurium, vecuronium and rocuronium as safe for use in people with MHS.
Surgery can be safely performed on people with MHS, but it’s important that the surgical team avoid the triggering agents and use the safe agents.
If an MH episode should occur, it must be identified and treated early in its course with intravenous dantrolene (Dantrium) and immediate supportive care in the operating room. Dantrolene, available in the United States since 1979, can stop an MH episode by interfering with muscle contraction, probably by blocking the release of calcium from inside the muscle fiber.
MHAUS doesn’t, however, recommend preventive treatment with dantrolene, and cautions that the drug can make muscle weakness worse in people with muscle disease.
Everyone with CCD is potentially susceptible to MH and should take appropriate precautions with surgery. Family members who seem unaffected by CCD could be MH-susceptible and should assume they are until proven otherwise by a muscle biopsy or genetic test.
MHAUS considers a caffeine/halothane contracture test (CHCT), performed on a muscle biopsy sample, to be the “gold standard” to diagnose MHS. False negatives (a determination that the person is not susceptible to MH when he really is) are rare, although false positives (a determination that someone is susceptible to MH when he really isn’t) are frequent, occurring about 20 percent of the time. MHAUS provides a list of centers capable of performing CHCTs.
The primary, but not the only, genetic cause of MHS is any of a number of mutations in the RYR1 gene, some of which also cause CCD. To be on the safe side, it’s wise to assume that any CCD-causing RYR1 mutation is a potential MHS mutation.
Importantly, MH reactions don’t always occur with the first exposure to inhaled anesthesia, so one event-free surgery is no proof that one does not have MH susceptibility.