Titration of the Microconstant of Effect-site for the Target-controlled Infusion of Propofol

Abstract

The effect-site concentration of anesthetic drug is calculated by the formula using the effect-site's microconstant (Ke0) during the target-controlled infusion which controls the syringe pump under the pharmacokinetic three-compartment model with the effect-site compartment, and the Ke0 also determines the dosage of bolus and infusion rate during the effect-site targeting. The Ke0 of propofol, intravenous sedatives, is reported from various researches with electroencephalogram and auditory evoked potential, but it is impossible to apply the value of Ke0 to different pharmacokinetic models or infusion patterns. So we titrated the Ke0 of propofol for the pharmacokinetic models which is incorporated in the commercially available target-controlled infusion system. ASA physical status Ⅰ, unpremedicated, 21-40 yr, 69 female patients scheduled for minor gynecologic surgery under general anesthesia were randomly assigned into the three different groups. Group Cp54, Cp61 and Cp86 were administrated the target plasma concentration of 5.4 ㎍/㎖, 6.1 ㎍/㎖ and 6.8 ㎍/㎖ of propofol for the induction of anesthesia. The time to loss of responsiveness (LOR) was measured by a blind investigator. We recalulated the effect-site concentration of propofol for LOR by a computer-simulation with increasing Ke0. And we evaluated the Ke0 for the minimal difference of effect-site concentration between group with the quadratic polynominal regression. The Ke0 of propofol for the same pharmacodynamic effect between group was 0.77 min-1 and the newly calculated effect-site concentrations of propofol for LOR were not significantly different between groups. The adequate Ke0 for the specific pharmacokinetic model will predict the accurate effect-site concentration and will be used for the parameter of effect-site targeting.