Effects of enzyme induction, renal and cardiac function on ketamine plasma kinetics in patients with ketamine long-term analgosedation.
Steady-state plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were determined in 4 different groups of a total of 27 patients with ketamine long-term analgosedation (1.1 - 1.3 mg/kg/h). In 9 of the patients who had normal liver and kidney function (group 1), steady-state levels after 3 days of continuous infusion were 1.2 +/- 0.3 micrograms/ml ketamine, 1.0 +/- 0.6 micrograms/ml norketamine, and 2.6 +/- 1.0 micrograms/ml dehydronorketamine. The measured ketamine levels in group 1 were in agreement with the expected value, which may be calculated from published pharmacokinetic data after bolus injection. In 8 patients with acute renal failure (group 2), a tendency to about 20% higher ketamine steady-state plasma levels compared to group 1 was observed, but this difference was not significant. However, dehydronorketamine plasma levels were significantly higher in this group. Only a minor fraction of the ketamine dose (10% and 4%) was eliminated during hemodialysis or hemofiltration treatment, respectively. Steady-state plasma levels in 5 patients with cardiogenic shock (group 3) did not differ significantly from those of group 1. In 5 patients with long-term use of barbiturates (group 4), steady-state plasma levels of ketamine were significantly lower compared to groups 1 and 3, most likely due to barbiturate-induced enzyme induction. Hyperdynamic circulatory reactions were not observed in any of the patients. Psychomimetic effects could be excluded in 16 of the patients and were unlikely in 6 patients. In 5 further patients, psychomimetic effects could not definitely be excluded due to difficulties in non-verbal communication.
Köppel
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Reanimationszentrum, Universitätsklinikum Rudolf Virchow, Freie Universität Berlin, Germany.
Arndt
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Ibe
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K
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000097:blood* / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood* / Q000494:pharmacology; D007649:Ketamine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000700:Analgesics; D006993:Hypnotics and Sedatives; D007649:Ketamine; C033419:norketamine