4-CHLORO-M-CRESOL TEST - A POSSIBLE SUPPLEMENTARY TEST FOR DIAGNOSIS OF MALIGNANT HYPERTHERMIA SUSCEPTIBILITY

Background: In vitro contracture test (IVCT) for diagnosis of MH in ou r laboratory has a sensitivity of 100% and a specificity of 93%. The r esults are equivocal in 10-15%, and supplementary tests may thus be re quired. We have tested the hypothesis that 4-chloro-m-cresol (4-cmc) m ay be useful for a supplementary test. Methods: Muscle from 41 consecu tive patients from 7 families undergoing diagnostic muscle biopsy with IVCT was exposed in vitro to increasing concentrations of 4-cmc (25, 50, 75, 100, 150, and 200 mu mol l(-1)), and the force development rec orded. Diagnosis of MH susceptibility was made with Standard halothane and caffeine tests and included as results MHS (MH susceptible), MHN (MH negative), and MHE (equivoval result). Results: At all concentrati ons of 4-cmc, the increase in baseline force was significantly greater in the MHS group compared to the MHN group (P<0.05). Muscle from 15 M H-susceptible (MHS) patients responded to 4-cmc with increasing force at a threshold concentration of 75 mu mol l(-1) or less, whereas muscl e from 23 MH-non-susceptible (MHN) patients had thresholds of 100 mu m ol l(-1) or more. The accuracy of the chlorocresol test was thus 100% ;(95% confidence limits 90.75-100%) at a threshold of 75 mu mol l(-1). Amplitude of contractures at 2 mmol l(-1) caffeine not different from contractures at 75 mu mol l(-1) of 4- cmc in either the MHS or the MH N group (P>0.05). Iri viz, vivo concentrations of chlorocresol from cl inical use of insulin and somatropin are estimated to be 20 times less than the threshold concentration and thus these drugs seem safe in MH patients. Conclusion: 4-chloro-m-cresol may be a suitable aid to clar ify puzzling results of standard testing of MH susceptibility.