MALIGNANT HYPERTHERMIA SUSCEPTIBILITY REVEALED BY THE INVITRO CONTRACTURE TEST

  • 1 December 1987
    • journal article
    • research article
    • Vol. 36  (12) , 685-691
Abstract
Though a malignant hyperthermia (MH) crisis is still a critical event during general anesthesia, recent developments in prophylaxis and treatment should help in avoiding fatal episodes. The best means to avoid MH episodes would be early recognition of MH susceptibility. Today the only reliable test to identify MH susceptibility is the in vitro contracture test. Thus, to diagnose MH susceptibility we performed this test on muscle biopsies from 26 individuals who: (1) had an event during general anesthesia that may have been indicative of MH (4 patients); (2) had a family member with a medical history of MH (20 patients); or (3) had unexplained elevated CK levels (1 patient). The criteria according to which patients were submitted to the testing are shown in detail in Table 1. We used the standardized version of the contracture test that has been proposed by the European Malignant Hyperpyrexia Group. Muscle biopsies (20-30 mm long, 8 mm diameter) were dissected into 8-10 small bundles (2-3 mm diameter) and tested within 3 h post-biopsy in four independent tissue baths with various concentrations of caffeine or halothane. According to the concentration of caffeine or halothane necessary to elicit contractures exceeding a predefined force threshold (20 mN), it was possible to classify the patients as MHS (MH-susceptible), MHE (equivocal), or MHN (negative). In addition to the in vitro test, clinical, laboratory, and neurophysiological data were collected from these patients and correlated with the individual test results (Table 2). Thirteen patients were classified as MHS, five were MHE, and seven patients MHN (Fig. 3). Only persons classified as MHN are considered to be not susceptible to MH; these are the only individuals who should receive standard general anesthesia, which may also employ "triggering agents" without precautions. The remaining individuals should be regarded as MH-susceptible in forthcoming surgical procedures and receive appropriate prophylaxis, monitoring and safe anesthesia. Of the MHS patients, 54% also had abnormal findings on clinical examination and/or elevated CK levels. The other MHS individuals (46%) were classified solely based on the results of the contracture test. We feel that the five patients classified as MHE in our study should be more correctly classified as MHS. This assumption is based on two observations: (1) all five patients had a contracture response in 2% halothane or less and we never observed a halothane contracture in normal controls, even at concentrations up to 4%; and (2) family members of the patients who had a contracture test were clearly classified as MHN or MHS, supporting the assumption that MHE is not a distinct genetic entity. In the future, better control of testing conditions, collecting of more data with the standardized in vitro test, and a definition of contracture threshold relative to the maximum force generated by 32 mM caffeine in a single preparation may lead to a reduction in the size of the MHE group.

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