Testing for Malignant Hyperthermia
Rosenberg H, Antognini J, Muldoon S. Anesthesiology 2002; 96:232-37.
Malignant hyperthermia syndrome is uniquely the domain of anesthesiologists. This channelopathy may remain clinically silent until the susceptible individual is exposed to certain anesthetic agents. Although exercise-induced rhabdomyolysis may be a sign of susceptibility, the diagnosis of MHS is most often considered during the development of a classic hypermetabolic episode following exposure to succinylcholine and/or potent inhalational agents. For this reason, the pursuit of accurate susceptibility testing is, arguably, the responsibility of all anesthesiologists.
In "Testing for Malignant Hyperthermia," the authors reviewed the status of current evaluations for this disorder. Clearly, the halothane-caffeine contracture test (HCCT) remains the standard diagnostic test.
In the North American testing protocol, 3% halothane or 0.5, 1, or 2mM caffeine is added to the solutions bathing viable (fresh) muscle strips attached to force transducers. Positive contractures are described as 0.7g to 3% halothane or 0.3g to caffeine. The European testing protocol results in more positives (or equivocal tests) than the North American. Furthermore, inter-center testing within Europe resulted in one study in a 12% discordance (that is, a positive in one center tests negative in another).
Other avenues for testing are discussed. Prominently featured is molecular genetic testing, which became promising with the discovery of the ryanodine receptor gene (RYR-1) mutation in MH-susceptible pigs. Complicating the application of genetic testing to humans, however, is the genetic heterogeneity of human MH. The presence of multiple mutations associated with MH makes DNA analysis unsuitable at present as a definitive diagnostic tool. (One exception may be the testing of first degree family members for a specific mutation previously identified in a known MH- positive patient.)
Creatine kinase often is chronically elevated in MH, but this is a non-specific finding. Nuclear magnetic resonance spectroscopy similarly may show abnormalities in MH-susceptible muscle, as well as in patients with other myopathies. Some work on RYR-1 receptors on human B cells, as well as MH-cultured muscle cells, may show increased intracellular calcium in in vitro testing.
Clearly at present, the HCCT remains the standard for MH testing. There are only twelve test centers in North America. It is expensive, in terms of travel, medical costs, and work time missed. The same biopsy may provide specimens with variable responsiveness. Ten to fifteen percent of patients tested have"intermediate" values. Procedural risks exist. Studies may be equivocal in patients with myopathies.
Why bother referring patients who have a suspicious episode (or their families) to an MH testing center? Why not simply use a "non-triggering" anesthetic for such patients? As suggested by the authors, the dilemma results from a critical need for scientific clarification of this syndrome. Until more refined testing is available, correlation between less invasive and/or more specific tests must be continuously re-evaluated. While the MH-susceptible pig model has advanced our understanding of this anesthesia-induced disorder, it is not identical to its human counterpart. Additionally, a negative HCCT test is considered fairly reliable, and may have implications for large numbers of family members. Furthermore, a positive test result might prompt a formal protocol for disseminating information among family members, wearing a medical identification tag, and providing responsible patient education.
Reviewed by: Julianne Bacsik, MD
Children's Hospital
Boston, MA
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