PHARMACOKINETIC MODEL SELECTION FOR TARGET CONTROLLED INFUSIONS OF PROPOFOL - ASSESSMENT OF 3 PARAMETER SETS

Background: Computer-assisted target controlled infusions (TCI) result In prediction errors that are influenced by pharmacokinetic variabili ty among and within patients. It Is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly Influences dru g concentrations and clinical acceptability. Methods: Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations wer e measured and prediction errors calculated from pooled and intrasubje ct data. Results: Arterial propofol concentrations in the Dyck group r evealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (m ean:47%) than the Marsh (29%) and Tackley (24%) groups. There was litt le tendency for measured concentrations to vary from targeted values o ver time (divergence). Variability about an observed mean in individua l patients (wobble) was low. Venous propofol concentrations were initi ally much less than arterial concentrations, but this difference decre ased over time. Conclusions: Although It may be preferable to administ er propofol TCI by using a locally derived parameter set, It Is accept able to use a model from elsewhere. The Marsh and Tackley models produ ced equally good performance and are appropriate for propofol TCI with in the range of 3-6 mu g/ml. The Dyck model was less accurate at maint aining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indic ators of performance, demonstrated differences among the parameter set s. Clinically, TCI worked well, and by clinical criteria, the choice o f pharmacokinetic model did not appear to make a difference.