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

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 microg x ml(-1) (group 1), while another 18 were induced with a target concentration of 6 microg x 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) microg x 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.