Preoperative creatine kinase blood levels and myopathological changes in malignant hyperthermia

Abstract

In malignant hyperthermia (MH) the fundamental lesion is located in skeletal muscle fibres. The underlying cause of MH is suggested to be an increase in myoplasmic calcium, which is released from the sarcoplasmic reticulum. Although MH is believed to represent myopathy, patients susceptible to MH (MHS) rarely have clinical evidence of muscle diseases [1]. Creatine kinase (CK) as muscle cell enzyme is reported to predict MH disposition when blood levels at rest are raised [2]. The purpose of this study was to determine, whether any clinical prediction could be made of abnormal pre-operative CK blood levels or whether there is a correlation between raised CK values and histological abnormalities. After institutional approval and written informed consent, 196 patients aged 3–71 years with clinical suspicion for MH were enrolled in this prospective study. The patients were first classified as MHS or MHN (MH non susceptible) by the caffeine halothane contracture test (CHCT) according to the European MH protocol [3]. Patients tested equivocal (MHE) were excluded from this study. Additionally, small muscle specimens (approximately 3×3×10 mm) were excised from each patient for histological and morphometric investigation. Preoperative levels of CK in blood were measured and compared both with the CHCT and the histological results. Data are expressed as mean ± SEM or percentages, respectively. Statistical analysis was performed using the Mann-Whitney U-test. P<0.05 was considered significant. 80 from the 196 patients in this study (40.8%) were diagnosed MHS and 116 (59.2%) MHN. In the MHS patients 26 from 80 (32.5%) had elevated CK values compared to 13 from 116 (11.2%) in the MHN group. 52 (65%) of the MHS patients showed myopathological changes (9 specific, 43 unspecific), whereas only 49 (42.2%) of the MHN patients had any myopathological abnormalities (3 specific, 46 unspecific). Preoperative CK blood levels were increased in 39 patients (19.9%) and two thirds of these were classified MHS. While 88 of all patients were female (44.9%) the distribution was a little different in the two diagnostic groups with 26 (32.5%) female MHS and 62 (53.4%) female MHN patients. It was noticed that only 7 of the 39 patients with raised CK were female (17.9%) and all of them showed myopathological abnormalities both in the MHS group (4 female) and in the MHN group (3 female). In contrast only 50% of the male patients with preoperative elevated CK values showed myopathological changes with no differences between MHS and MHN. The results demonstrate that it is not possible to distinguish MHS from MHN individuals by determining the CK blood levels at rest or using histological techniques. At present, the CHCT remains the only reliable test method for the diagnosis of MH susceptibility. There were significantly more male than female patients with elevated CK values. A further significant difference was that 100% of the females but only 50% of the male patients with elevated CK values showed myopathological abnormalities. We recommend that all patients with increased CK levels at rest should have muscle biopsy both for MH diagnostic and histological investigation.