Computer-controlled infusion of alfentanil for postoperative analgesia. A pharmacokinetic and pharmacodynamic evaluation.
BACKGROUND
Although computer-controlled infusion (CCI) of alfentanil has been shown to be effective intraoperatively, this technique has not been validated for postoperative use. Therefore, the authors examined the efficacy of this technique in providing postoperative pain relief. The study comprised both a validation of published pharmacokinetic data sets and the definition of the minimum effective analgesic concentrations after major orthopedic surgery.


METHODS
The bias and inaccuracy of the implemented pharmacokinetic data set were examined, in 20 patients who had undergone major orthopedic surgery, by determination of the median performance error (MDPE) and median absolute performance error (MDAPE). The performance of two other published pharmacokinetic data sets was also examined by simulating the plasma concentrations that would have been predicted, had these data sets been implemented. The minimum effective analgesic concentrations (MEAC) were determined at the following time points: at the onset of pain, at 9:00 PM on the day of surgery, and at 9:00 AM and 9:00 PM on the first postoperative day.


RESULTS
Measured plasma concentration-time profiles generally were parallel to the target concentration-time profiles. The MDPE and MDAPE obtained were 12% and 28%, respectively. The MEACs ranged from < 1 to 175 ng/ml and showed substantial interindividual variability. The median MEACs at the four study times were 59, 52, 65, and 43 ng/ml. The MEAC at 9:00 PM on the first postoperative day was significantly lower than those at the other study times (P < 0.05).


CONCLUSIONS
Computer-controlled infusion of alfentanil provides adequate postoperative analgesia. The study demonstrated that pharmacokinetic data sets that are useful for intraoperative CCI of alfentanil are equally valid in the postoperative phase. Although required plasma concentrations of alfentanil are reasonably stable in time, interindividual variations are large, necessitating individual titration.
van den Nieuwenhuyzen
M C
MC
Department of Anaesthesiology, University Hospital Leiden, The Netherlands.
Engbers
F H
FH
Burm
A G
AG
Lemmens
H J
HJ
Vletter
A A
AA
van Kleef
J W
JW
Bovill
J G
JG
D000328:Adult; D000368:Aged; D015760:Alfentanil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004360:Drug Therapy, Computer-Assisted; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000517:prevention & control*
D015760:Alfentanil