Population pharmacodynamics and pharmacokinetics of remifentanil as a supplement to nitrous oxide anesthesia for elective abdominal surgery.
BACKGROUND
Remifentanil blood concentrations necessary for adequate intraoperative anesthesia have not been defined. The goal of this study was to determine the blood concentrations of remifentanil needed for anesthesia with 66% nitrous oxide during intraabdominal surgery. In addition, the pharmacokinetics of remifentanil and the effects of covariates on both the pharmacodynamics and the pharmacokinetics were determined.


METHODS
Anesthesia was induced and maintained with 66% nitrous oxide in oxygen and remifentanil. Remifentanil was administered by a computer-controlled infusion pump that rapidly attained, and then maintained, constant remifentanil blood concentrations. If the patient showed signs of inadequate anesthesia (autonomic or somatic response), the target concentration was increased by 1 or 2 ng/ml. If no response occurred during a 15-min period, the concentration was decreased by 1 or 2 ng/ml. Remifentanil pharmacodynamics and pharmacokinetics were estimated using NONMEM.


RESULTS
The remifentanil blood concentration for which there is a 50% probability of adequate anesthesia during abdominal surgery (Cb50) with 66% nitrous oxide was 4.1 ng/ml in men and 7.5 ng/ml in women. The Cb50 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-compartment model with lean body mass as a significant covariate, where V1 = 0.129(lean body mass-50) + 3.79 l, V2 = 6.87 l, CL1 = 0.0389(lean body mass-50) + 2.34 l/min and CL2 = 1.14 l/min.


CONCLUSIONS
The Cb50 differed according to patient gender. However, because surgery type was not specified for each man or woman, this may reflect a difference in surgical procedure.
Drover
D R
DR
Department of Anesthesia, Stanford University School of Medicine, California, USA. ddrover@leland.stanford.edu
Lemmens
H J
HJ
D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004360:Drug Therapy, Computer-Assisted; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D009609:Nitrous Oxide; D010880:Piperidines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077208:Remifentanil
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D010880:Piperidines; D009609:Nitrous Oxide; D000077208:Remifentanil