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 no t been validated for postoperative use. Therefore, the authors examine d the efficacy of this technique in providing postoperative pain relie f. The study comprised both a validation of published pharmacokinetic data sets and the definition of the minimum effective analgesic concen trations after major orthopedic surgery. Methods: The bias and inaccur acy of the implemented pharmacokinetic data set were examined, in 20 p atients who had undergone major orthopedic surgery, by determination o f 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 th at would have been predicted, had these data sets been implemented. Th e minimum effective analgesic concentrations (MEAC) were determined at the following time points: at the onset of pain, at 9:00 PM on the da y of surgery, and at 9:00 AM and 9:00 PM on the first postoperative da y. Results. Measured plasma concentration-time profiles generally were parallel to the target concentration-time profiles. The MDPE and MDAP E obtained were 12% and 28%, respectively. The MEACs ranged from < 1 t o 175 ng/ml and showed substantial interindividual variability. The me dian 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). Conclusion: Computer- controlled infusion of alfentanil provides adequate postoperative anal gesia. The study demonstrated that pharmacokinetic data sets that are useful for intraoperative CCI of alfentanil are equally valid in the p ostoperative phase. Although required plasma concentrations of alfenta nil are reasonably stable in time, interindividual variations are larg e, necessitating individual titration.