Equivalent analgesia and side effects during epidural and pharmacokinetically tailored intravenous infusion with matching plasma alfentanil concentration

Background Recently, several clinical studies comparing intravenous and epi dural infusions of fentanyl and its derivatives suggested that epidural inf usions act primarily by systemic absorption to produce supraspinal analgesi a. To evaluate this hypothesis, the authors used pharmacokinetically tailor ed intravenous infusions to produce matching plasma alfentanil concentratio ns during epidural and intravenous administration. The analgesia and side e ffects achieved with each mode of administration were compared. Methods: Twelve volunteers participated in this placebo-controlled crossove r study. The pain model was cutaneous electric stimulation of the finger an d toe. The test battery included subjective rating of pain intensity; end-t idal carbon dioxide level; pupil size; ratings of alertness, nausea, and pr uritus; and a plasma alfentanil assay. On one test day, the participants re ceived epidural alfentanil (400 mu g bolus + a 400-mu g/h infusion for 2 h) and an intravenous saline infusion. The test battery was administered at r egular intervals. On another test day, the participants received epidural s aline and a computer-controlled intravenous infusion of alfentanil. The tes ting protocol was repeated as on the first test day. On the day the placebo was administered, the participants received epidural and intravenous salin e infusions. The order of the placebo day was randomized. Results: Plasma alfentanil concentration-time profiles were identical durin g epidural and intravenous infusions. A nearly equivalent analgesic respons e was observed with epidural and intravenous alfentanil at the upper and lo wer extremities. There were no differences in side effects for epidural and intravenous administration. Conclusions: The systemic redistribution of alfentanil accounts for most of the analgesia and effects produced by epidural infusion.