A-76
2002
Comparison of the In-Vitro Effects of Dibucaine on Skeletal Muscle Specimens from Malignant Hyperthermia Susceptible and Normal Patients
Mark U. Gerbershagen, M.D.; Frank Wappler, M.D., Ph.D.; Marko Fiege, M.D.; Ralf Weisshorn, M.D.; Jochen Schulte am Esch, M.D., Ph.D.
Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Introduction: Malignant hyperthermia is caused by a pathological regulation of the Ca2+ homeostasis as a result of an altered ryanodine receptor of the skeletal muscle cell (1). The local anesthetic dubucaine enhances the rate of Ca2+-induced Ca2+-release from the skeletal muscle sarcoplasmic reticulum (2). Thus, the question was raised, whether an in-vitro contracture test (IVCT) with dibucaine is able to distinguish between MH susceptible (MHS) and MH normal. The IVCT with dibucaine revealed marked contractures in MHS but only small contractures in MHN porcine skeletal muscle specimens (3). The present study, therefore, examines the in-vitro effects of dibucaine in human muscle preparations.

Methods: After institutional approval and informed consent 20 patients undergoing IVCT according to the European MH Group (4) for MH diagnostics were included in this study. In muscle preparations surplus to standard diagnostic requirements dibucaine was administered in concentrations of 0.2 respectively 0.3 mmol/l. The effects on contracture development and muscle twitch were observed for 60 min. Data are presented as medians and ranges. Statistical significance (p<0.05) was analysed using the Wilcoxon test.

Results: Eight patients were diagnosed as MHS and twelve patients as MHN by the standard IVCT. Neither dibucaine concentration induced contractures in MHS as well as in MHN preparations. The twitch response, however, lowered significantly after dibucaine in both diagnostic groups (see Table 1).Conclusion: In contrast to known MH trigger agents bolus administration of 0.2 and 0.3 mmol/l dibucaine did not induce contractures in human MHS muscle specimens. Dibucaine produced a negative inotropic effect in all skeletal muscle preparations, which could be a result of the sodium channel blocking capacity. Further studies should examine whether differing concentrations of dibucaine enable in-vitro differentiation between human MHS and MHN specimens.

Literatur:

1. Physiol Rev 1996; 76:537-588

2. Biomedical Res 1980; 1: 269-272

3. Anästhesiol Intensivmed 1999; 40: 392

4. Acta Anaesthesiol Scand 1997; 41: 955-966

Anesthesiology 2002; 96: A76
Table 1: Muscle twitch amplitude in mN before (=0 min) and 10 min after adiministration of 0.2 resp. 0.3 mmol/l dibucaine
Dibucaine0 min - 0.2 mmol/l10 min - 0.2 mmol/l0 min - 0.3 mmol/l10 min - 0.3 mmol/l
MHS (n=8) med/min/max39.7/15.5/75.0*10.9/5.1/38.3*22.6/10.3/71.2*5.1/0.0/44.2*
MHN (n=12) med/min/max40.4/14.9/92.722.7/7.3/52.149.2/10.0/101.717.5/1.6/45.6

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