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

Abstract

Background. In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce PROP), 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 k e0=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. © The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.