The Site of Action of Epidural Fentanyl in Humans: The Difference Between Infusion and Bolus Administration

Most published studies suggesting that epidural fentanyl acts predominantly at spinal sites administered the drug as a bolus injection, whereas most studies suggesting that it acts predominantly at supraspinal sites administered the drug as an infusion. In this study we tested the hypothesis that the mode of administration (bolus versus infusion) of epidural fentanyl determines its site of action. Ten healthy volunteers were enrolled in this randomized, double-blinded, cross-over study. On separate study days fentanyl was administered into the epidural space as a bolus (0.03 mg followed by 0.1 mg 210 min later) and as an infusion (0.03 mg/h followed by 0.1 mg/hr 210 min later for 200 min). Using a thermal and electrical experimental pain model, the heat (°C) and electrical current (mA) causing maximum tolerable pain were assessed repetitively over a period of 420 min. The analgesic efficacy measures were obtained at a lumbar and a cranial dermatome. Plasma fentanyl concentrations were determined throughout the study. Epidural bolus administration of fentanyl resulted in segmental analgesia (leg > head), whereas the epidural infusion of fentanyl produced nonsegmental analgesia (leg = head). There was a significant linear relationship between the analgesic effect and the plasma concentration of fentanyl for the epidural infusion but not for the epidural bolus administration of fentanyl. These findings support our hypothesis and might explain the apparent conflict in the literature regarding the site of action of epidural fentanyl.