Vuyk J. Lim T. Engbers FH. Burm AG. Vletter AA. Bovill JG.
Institution
Department of Anaesthesiology, University Hospital Leiden, The
Netherlands.
Title
The pharmacodynamic interaction of propofol and alfentanil during lower
abdominal surgery in women.
Source
Anesthesiology. 83(1):8-22, 1995 Jul.
Abstract
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. DISCUSSION: 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.