Journal Article

Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic–dynamic models

M. Coppens, J. G. M. Van Limmen, T. Schnider, B. Wyler, S. Bonte, F. Dewaele, M. M. R. F. Struys and H. E. M. Vereecke

in BJA: British Journal of Anaesthesia

Published on behalf of the British Journal of Anaesthesia

Volume 104, issue 4, pages 452-458
Published in print April 2010 | ISSN: 0007-0912
Published online February 2010 | e-ISSN: 1471-6771 | DOI: https://dx.doi.org/10.1093/bja/aeq028
Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic–dynamic models

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Background

In the ideal pharmacokinetic–dynamic (PK–PD) model for calculating the predicted effect-site concentration of propofol (CePROP), for any CePROP, the corresponding hypnotic effect should be constant. We compared three PK–PD models (Marsh PK with Shüttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms.

Methods

We randomized 60 patients to Group M (Marsh's model with ke0=0.26 min−1), Group S1 or Group S2 (Schnider's model with a fixed ke0=0.456 min−1 or a ke0 adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding CePROP, as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if CePROP remains constant over time.

Results

All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant CePROP, at a more pronounced level of hypnotic drug effect than intended.

Conclusions

Targeting CePROP at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.

Keywords: drug delivery, computerized; model, pharmacodynamic; model, pharmacokinetic; pharmacology, propofol; monitoring, depth of anaesthesia

Journal Article.  3168 words.  Illustrated.

Subjects: Anaesthetics

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