POPULATION PHARMACODYNAMICS AND PHARMACOKINETICS OF REMIFENTANIL AS ASUPPLEMENT TO NITROUS-OXIDE ANESTHESIA FOR ELECTIVE ABDOMINAL-SURGERY

Background: Remifentanil blood concentrations necessary for adequate i ntraoperative anesthesia have not been defined. The goal of this study was to determine the blood concentrations of remifentanil needed for anesthesia with 69% nitrous oxide during intraabdominal surgery. La ad dition, the pharmacokinetics of remifentanil and the effects of covari ates on both the pharmacodynamics and the pharmacokinetics were determ ined. Methods: Anesthesia was induced and maintained with 66% nitrous oxide in oxygen and remifentanil, Remifentanil was administered by a c omputer-controlled infusion pump that rapidly attained, and then maint ained, constant remifentanil blood concentrations. If the patient show ed signs of inadequate anesthesia (autonomic or somatic response), the target concentration was increased by 1 or 2 ng/ml. If no response oc curred during a 15-min period, the concentration was decreased by 1 or 2 ng/ml. Remifentanil pharmacodynamics and pharmacokinetics were esti mated using NONMEM. Results: The remifentanil blood concentration for which there is a 50% probability of adequate anesthesia during abdomin al surgery (C-b50) with 66% nitrous oxide was 4.1 ng/ml in men and 7.5 ng/ml in women. The C-b50 values for prostatectomy, nephrectomy, and other abdominal procedures were 3.8, 5.6, and 7.5 ng/ml, respectively. Remifentanil pharmacokinetics were best described by a two-compartmen t model with lean body mass as a significant covariate, where V-1 = 0. 129(lean body mass-50) + 3.79 1, V-2 = 6.87 1, CL1 = 0.0389(lean body mass-50) + 2.34 1/min and CL2 = 1.14 1/min, Conclusions: The C-b50 dif fered according to patient gender. However, because surgery type was n ot specified for each man or woman, this may reflect a difference in s urgical procedure.