Endotoxin-induced Fever Increases the Clearance of Methohexitone in Rabbits

Abstract

Abstract We have previously observed that the clearance of methohexitone, given by continuous infusion for sedation in the intensive care unit, was influenced by body temperature in patients with post-operative fever. The aim of the present study was to reproduce this finding in an animal model that can then be used to predict similar influences for other anaesthetic agents. Sixteen rabbits were infused for 2·0 h with methohexitone (8·4 ± 0·5 mg kg−1 h−1 (mean ± s.d.)) and in eight of them fever was induced with intravenous Escherichia coli endotoxin. Arterial blood samples were taken over 6 h and plasma concentrations of methohexitone were assayed by gas chromatography. The mean body temperatures of the rabbits over the periods of measurement varied between 38·5 and 41·8°C, and the total clearance of methohexitone (mean 50·7 mL min−1 kg−1) was positively correlated with temperature (r = 0·545, P = 0029). No significant correlations with temperature were found for other pharmacokinetic parameters. We conclude that these observations correspond to the findings in the clinical pharmacokinetic study, showing the validity of the animal model.