4-Chloro-m-cresol test--a possible supplementary test for diagnosis of malignant hyperthermia susceptibility

In vitro contracture test (IVCT) for diagnosis of MH in our laboratory has a sensitivity of 100% and a specificity of 93%. The results are equivocal in 10-15%, and supplementary tests may thus be required. We have tested the hypothesis that 4-chloro-m-cresol (4-cmc) may be useful for a supplementary test.

Muscle from 41 consecutive 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 mumol l-1), and the force development recorded. 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).

At all concentrations 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 MH-susceptible (MHS) patients responded to 4-cmc with increasing force at a threshold concentration of 75 mumol l-1 or less, whereas muscle from 23 MH-non-susceptible (MHN) patients had thresholds of 100 mumol l-1 or more. The accuracy of the chlorocresol test was thus 100% (95% confidence limits 90.75-100%) at a threshold of 75 mumol l-1. Amplitude of contractures at 2 mmol l-1 caffeine was not different from contractures at 75 mumol l-1 of 4-cmc in either the MHS or the MHN group (P > 0.05). In vivo concentrations of chlorocresol from clinical 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.

4-chloro-m-cresol may be a suitable aid to clarify puzzling results of standard testing of MH susceptibility.