Precision and bias of target controlled propofol infusion for sedation

Background. The purpose of this study is to test precision andsystematic bias of a target controlled infusion (TCI) of propofolin human volunteers at two sedative concentrations. Methods. We studied the ‘Diprifusor’ model (MarshPharmacokinetics and a Graseby® 3400 infusion pump) in 18human volunteers at two sedative target plasma concentrations(0.5 and 1.0 µg ml^–1). Twenty minutes after infusionstart or change and 20 min after discontinuation of the infusionplasma propofol concentrations were measured using liquid chromatography–massspectroscopy (LC-MS). Plasma propofol concentrations were comparedwith concentrations predicted by the TCI system. Agreement ofthose two measures (precision and bias) was determined usingregression analysis. Results. We found little systematic bias but poor precision.When setting the TCI system to deliver a plasma concentrationof 1.0 µg ml^–1 one can predict the actual plasmaconcentration with 95% confidence only within a range of 0.44–1.38µg ml^–1. Conclusions. This finding helps to explain differences in responsesto propofol sedation; pharmacokinetic variability appears tobe an important factor.