Effect-compartment equilibrium rate constant (k_eo) for propofol during induction of anesthesia with a target-controlled infusion device

Abstract

The effect-compartment concentration (C_e) of a drug at a specific pharmacodynamic endpoint should be independent of the rate of drug injection. We used this assumption to derive an effect-compartment equilibrium rate constant (k_eo) for propofol during induction of anesthesia, using a target controlled infusion device (Diprifusor). Eighteen unpremedicated patients were induced with a target blood propofol concentration of 5 μg · ml⁻¹ (group 1), while another 18 were induced with a target concentration of 6 μg · ml⁻¹ (group 2). The time at loss of the eyelash reflex was recorded. Computer simulation was used to derive the rate constant (k_eo) that resulted in the mean C_e at loss of the eyelash reflex in group 1 being equal to that in group 2. Using this population technique, we found the k_eo to be 0.57 min⁻¹. The mean (SD) effect compartment concentration at loss of the eyelash reflex was 2.39 (0.70) μg · ml⁻¹. This means that to achieve a desired C_e within 3 min of induction, the initial target blood concentration should be set at 1.67 times that of the desired C_e for 1 min, after which it should revert to the desired concentration.