Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia.
BACKGROUND
Propofol and alfentanil often are combined during induction of anesthesia. However, the interaction between these agents during induction has not been studied in detail. The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex, loss of consciousness, and hemodynamic function in 20 unpremedicated ASA physical status 1 patients aged 20-55 yr.


METHODS
Patients were randomly divided into four groups to receive a computer- controlled infusion of alfentanil with target concentrations of 0, 50, 200, or 400 ng/ml (groups A, B, C, and D, respectively). While the target concentration of alfentanil was maintained constant, patients received a computer- controlled infusion of propofol, with an initial target concentration of 0.5-1 microgram/ml, that was increased every 12 min by 0.5-1 microgram/ml. Every 3 min, the eyelash reflex and state of consciousness were tested an an arterial blood sample was taken for blood propofol and plasma alfentanil determination. The propofol-alfentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression, and for the percentage of change in systolic blood pressure and heart rate by logistic regression.


RESULTS
The patient characteristics did not differ significantly among the four groups. The patients in groups A and B continued to breathe adequately, whereas all patients in groups C and D required assisted ventilation. End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the EC(50) of propofol decreased from 2.07 to 0.83 microgram/ml for loss of eyelash reflex and from 3.62 to 1.55 microgram/ml for loss of consciousness. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the blood propofol concentrations associated with a 10% decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 microgram/ml and from 2.36 to 0.04 microgram/ml, respectively.


CONCLUSIONS
Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness. In addition, alfentanil enhances the depressant effects of propofol on systolic blood pressure and heart rate. Hemodynamic stability, therefore, does not increase in patients receiving propofol in combination with alfentanil compared to those receiving propofol as the sole agent for induction of anesthesia.
Vuyk
J
J
Department of Anaesthesiology, University Hospital Leiden, The Netherlands.
Engbers
F H
FH
Burm
A G
AG
Vletter
A A
AA
Griever
G E
GE
Olofsen
E
E
Bovill
J G
JG
D000328:Adult; D015760:Alfentanil / Q000097:blood / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000097:blood / Q000494:pharmacology*; D001767:Blinking / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000097:blood / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D015760:Alfentanil; D015742:Propofol