Spinal Mechanisms Contribute to Analgesia Produced by Epidural Sufentanil Combined with Bupivacaine for Postoperative Analgesia Jean L. Joris, MD, PhD*, Eric A. Jacob, MD*, Daniel I. Sessler, MD†, Jean-Franc ¸ois J. Deleuse, MD*, Abdourahamane Kaba, MD*, and Maurice L. Lamy, MD* *Department of Anesthesia and Intensive Care Medicine and †the Outcomes Research ® Institute and Department of Anesthesiology, University of Louisville, Louisville, Kentucky When used alone, lipid-soluble epidural opioids are thought to produce analgesia supraspinally via systemic absorption. However, spinal opioids and local anesthetics have been shown to act synergistically at the spinal level in animal studies. We, therefore, tested the hypothesis that sufentanil requirements will be less when given epi- durally than IV in patients simultaneously given epidural bupivacaine after major abdominal surgery. Forty pa- tients were anesthetized with isoflurane and epidural bu- pivacaine for major abdominal surgery. After surgery, each was given a continuous epidural infusion of bupiva- caine at a rate of 5 mg/h and sufentanil patient-controlled analgesia (PCA). In a randomized, double-blinded fash- ion, the sufentanil was given either epidurally or IV. PCA settings were the same in each group. For 60 hrs after sur- gery, the following variables were measured: pain scores at rest, during mobilization, and during coughing; exten- sion of sensory block; side effects; and sufentanil con- sumption. Pain scores, extension of sensory block, and the incidence of side effects did not differ between the two groups. Consumption of sufentanil in the epidural group was half that of the IV group (48 h after surgery: 107  57 g versus 207  100 g for the epidural and IV groups, respectively; P  0.05). We conclude that spinal mecha- nisms contribute to the analgesia produced by epidural sufentanil in combination with a local anesthetic. (Anesth Analg 2003;97:1446 –51) S ufentanil, a lipophilic opioid, is often given epi- durally for postoperative (1,2) and labor (3) an- algesia. Lipophilic opioids such as fentanyl and sufentanil are used instead of hydrophilics such as morphine because it is thought that their lipophilicity allows them to act segmentally on opioid receptors in the dorsal horn of the spinal cord, thus minimizing supraspinal side effects. However, whether epidurally administered sufentanil acts spinally or supraspinally via systemic absorption remains controversial. For ex- ample, epidural boluses of sufentanil exceeding 10 g produce analgesia via a spinal mechanism (4 – 6). In contrast, analgesia from a continuous infusion of small-dose sufentanil appears to result primarily from systemic absorption of the opioid with subsequent recirculation to supraspinal centers (7–9). In one study, even more epidural than IV sufentanil was required to provide comparable postoperative pain relief, apparently because the drug was sequestered in fat tissue surrounding the epidural space (10). Epidural opioids are often combined with small doses of local anesthetic because these combinations might improve postoperative outcome (11) and pro- vide better analgesia during mobilization than opioid alone (12). Furthermore, the addition of opioid to local anesthetic allows a reduction in the dose of each; consequently, the risk of side effects from either drug is reduced (13). Animal studies suggest that small doses of a local anesthetic and an opioid such as morphine (14,15) or sufentanil (16) interact synergistically at the spinal level when both are given spinally or epidurally. These data suggest that, when combined with local anesthesia, epidural sufentanil administration will be more effective than IV administration—although sufentanil is otherwise of roughly comparable efficacy Supported in part by National Institutes of Health Grant GM 58273 (Bethesda, MD) and the Commonwealth of Kentucky Re- search Challenge Trust Fund (Louisville, KY). None of the authors has any personal financial interest related to this research. Presented in part at the annual meeting of the European Society of Anaesthesiologists, Barcelona, Spain, April 25–28, 1998. Accepted for publication June 3, 2003. Address correspondence to Jean L. Joris, MD, PhD, Department of Anesthesia and Intensive Care Medicine, CHU de Lie `ge, Domaine du Sart-Tilman, B-4000 Lie `ge, Belgium. Address e-mail to Jean. Joris@chu.ulg.ac.be. Reprints will not be available from the author. DOI: 10.1213/01.ANE.0000082251.85534.84 ©2003 by the International Anesthesia Research Society 1446 Anesth Analg 2003;97:1446–51 0003-2999/03