Pharmacology of epidural fentanyl, alfentanil, and sufentanil in volunteers

Abstract

Background: Despite a large number of clinical investigations in postoperative patients, the pharmacology of epidural fentanyl, alfentanil, and sufentanil has not been well characterized in a human laboratory setting. In this double-blind, placebo-controlled crossover study, we evaluated analgesia and side effects produced by epidural fentanyl (30 and 100 micrograms), alfentanil (300 and 1,000 micrograms), and sufentanil (3 and 10 micrograms) in volunteers.

Methods: Each of 12 volunteers participated in four separate study sessions. The pain model was cutaneous electrical stimulation of intensity sufficient to produce a pain report of 5 on a 0-5 scale, delivered alternately to the finger and tow. Ventilatory drive, pupil size, and subjective ratings of alertness, nausea, and pruritus were measured using visual analog scales. On each study day, after baseline measurements, an epidural catheter was placed at the L2-L3 or L3-L4 interspace. Subjects received the small dose of study drug, and the tests were repeated at 2, 55, and 95 min after drug administration. Subjects then received the large dose of the same study drug, and the series of tests was repeated at 2, 55, and 95 min later. Plasma opioid concentrations were measured using gas chromatography-mass spectrometry.

Results: Dose-dependent analgesia was found for all study opioids. For both doses of all opioids, toe analgesia was significantly greater than finger analgesia. Epidural fentanyl and alfentanil provided greater analgesia than sufentanil at the doses investigated. Sedation, increased end-tidal carbon dioxide, and pupillary constriction occurred only after the large epidural doses of all opioids. Overall, the incidence of subjective side effects was low, but four subjects experienced pruritus after 100 micrograms fentanyl, and four were nauseated after 1,000 micrograms alfentanil. Plasma opioid concentrations were near minimum effective analgesic plasma concentrations only after larger epidural doses.

Conclusions: Lumbar epidural fentanyl, alfentanil, and sufentanil produce selective lower-extremity analgesia. Low plasma opioid concentrations measured after small epidural opioid doses suggest a spinal mechanism for analgesia. Larger doses of epidural opioids result in systemic absorption and are likely to produce supraspinal analgesia and other side effects.