Target-controlled infusion of alfentanil for postoperative analgesia: contribution of plasma protein binding to intra-patient and inter-patient variability

We have examined the influence of plasma protein binding on inter-individua l and intraindividual variability in the effective postoperative analgesic concentration (EAC) of alfentanil and on the performance of the target-cont rolled infusion system used. Ten patients received standardized anaesthesia and target-controlled alfentanil for postoperative analgesia. Analgesia wa s assessed using a visual analogue scale (VAS). Plasma protein binding of a lfentanil was assessed at four different times (on arrival in the recovery room, at 21:00 on the day of surgery and at 09:00 and 21:00 on the first po stoperative day). Bias and inaccuracy were examined on the day of surgery a nd on the first postoperative day. Unbound fractions of alfentanil varied f rom 5 to 15% and varied in time. in general, the unbound fractions on the d ay of surgery were higher than those on the first postoperative day. Thirty -nine percent of inter-individual variability in the EAC of alfentanil (ran ge 33-140 ng m(-1)) at the onset of therapy could be explained by protein b inding. At the other observation times, correlations between unbound fracti on and EAC were only moderate. Bias on the day of surgery was -19% and 12% on the first postoperative day (ns). inaccuracy was 23% and 18%, respective ly (ns). We conclude that inter-individual variations in plasma protein bin ding can explain a significant portion of inter-individual variability in t he EAC of alfentanil in the early postoperative phase.