The pharmacodynamic interaction of propofol and alfentanil during lower abdominal surgery in women.
BACKGROUND
Propofol and alfentanil are frequently combined to provide general anesthesia. The purpose of this study was to characterize the pharmacodynamic interaction between propofol and alfentanil for several clinically relevant end points.


METHODS
Twenty-one women, aged 20-55 yr, scheduled for lower abdominal surgery, were randomly assigned in a double-blind manner to one of three groups to receive a computer-controlled infusion of propofol with target concentrations of 2, 4, or 6 micrograms/ml. In addition, all patients received computer-controlled infusion of alfentanil (initial target concentration 50 ng/ml). While the target concentration of propofol was maintained constant, the target concentration of alfentanil was varied in steps of 10-50 ng/ml according to the presence or absence of patient responses to perioperative stimuli. Arterial blood samples for alfentanil and propofol determination were taken at clinically relevant stimuli. Alfentanil-propofol interactions for laryngoscopy, intubation, skin incision, the opening of the peritoneum, and awakening were determined by logistic regression over the three groups (n = 21). The alfentanil concentrations associated with a 50% probability (EC50s) of suppression of responses to intraabdominal surgical stimuli, as determined by logistic regression in the individual patients, were related to corresponding mean blood propofol concentrations by nonlinear regression analysis.


RESULTS
With blood propofol concentrations increasing from 2 to 10 micrograms/ml, the EC50 of alfentanil decreased from 170 to 25 ng/ml for laryngoscopy, from 280 to 23 ng/ml for intubation, from 259 to 9 ng/ml for the opening of the peritoneum, and from 209 to 16 ng/ml for the intraabdominal surgical stimuli. With plasma alfentanil concentrations increasing from 10 to 150 ng/ml, the EC50 of propofol for the regaining of consciousness decreased from 3.8 to 0.8 microgram/ml.


CONCLUSIONS
We defined the pharmacodynamic interaction between propofol and alfentanil for suppression of responses to perioperative stimuli during lower abdominal surgery. We conclude that propofol reduces alfentanil requirements for all studied clinical end points. In addition, alfentanil decreases propofol concentrations at which patients regain consciousness.
Vuyk
J
J
Department of Anaesthesiology, University Hospital Leiden, The Netherlands.
Lim
T
T
Engbers
F H
FH
Burm
A G
AG
Vletter
A A
AA
Bovill
J G
JG
D000005:Abdomen / Q000601:surgery; D000328:Adult; D015760:Alfentanil / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D015742:Propofol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D015760:Alfentanil; D015742:Propofol