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, H. E. M. Vereecke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce(PROP)), for any Ce(PROP), the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shuttler 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.

We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) 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 Ce(PROP), 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 Ce(PROP) remains constant over time.

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 Ce(PROP), at a more pronounced level of hypnotic drug effect than intended.

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

Original languageEnglish
Pages (from-to)452-458
Number of pages7
JournalBritish Journal of Anaesthesia
Volume104
Issue number4
DOIs
Publication statusPublished - Apr-2010

Keywords

  • drug delivery
  • computerized
  • model
  • pharmacodynamic
  • model
  • pharmacokinetic
  • pharmacology
  • propofol
  • monitoring
  • depth of anaesthesia
  • PHARMACODYNAMICS
  • VOLUNTEERS
  • ANESTHESIA
  • INFUSION

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