Predictive ability of propofol effect-site concentrations during fast and slow infusion rates

The performance of propofol effect-site pharmacokinetic models during target-controlled infusion (TCI) might be affected by propofol administration rate. This study compares the predictive ability of three effect-site pharmacokinetic models during fast and slow infusion rates, utilizing the cerebral state index (CSI) as a monitor of consciousness.

Sixteen healthy volunteers, 21-45 years of age, were randomly assigned to receive either a bolus dose of propofol 1.8 mg/kg at a rate of 1200 ml/h or an infusion of 12 mg/kg/h until 3-5 min after loss of consciousness (LOC). After spontaneous recovery of the CSI, the bolus was administered to patients who had first received the infusion and vice versa. The study was completed after spontaneous recovery of CSI following the second dose scheme. LOC was assessed and recorded when it occurred. Adequacies of model predictions during both administration schemes were assessed by comparing the effect-site concentrations estimated at the time of LOC during the bolus dose and during the infusion scheme.

LOC occurred 0.97 +/- 0.29 min after the bolus dose and 6.77 +/- 3.82 min after beginning the infusion scheme (P<0.05). The Ce estimated with Schnider (ke0=0.45/min), Marsh (ke0=1.21/min) and Marsh (ke0=0.26/min) at LOC were 4.40 +/- 1.45, 3.55 +/- 0.64 and 1.28 +/- 0.44 microg/ml during the bolus dose and 2.81 +/- 0.61, 2.50 +/- 0.39 and 1.72 +/- 0.41 microg/ml, during the infusion scheme (P<0.05). The CSI values observed at LOC were 70 +/- 4 during the bolus dose and 71 +/- 2 during the infusion scheme (NS).

Speed of infusion, within the ranges allowed by TCI pumps, significantly affects the accuracy of Ce predictions. The CSI monitor was shown to be a useful tool to predict LOC in both rapid and slow infusion schemes.