BACKGROUND Opioids are thought to have equal analgesic effects when equivalent doses are used. However, sufentanil may achieve maximum effect while occupying fewer spinal opioid receptors (higher intrinsic efficacy). Therefore, sufentanil may be more effective than morphine when administered intraspinally in opioid-tolerant patients. METHODS This study evaluated 20 chronic cancer pain patients who underwent abdominal surgery for tumor resection. All patients used large doses of morphine (> 250 mg/day-1) preoperatively for 3 months or longer. Intraoperatively, patients received combined general-epidural anesthesia with 0.5% bupivacaine and 0.02% morphine at 8 ml/h-1. Postoperative continuous epidural analgesia with 0.1% bupivacaine and 0.02% morphine at 5 ml/h-1 plus intravenous patient-controlled analgesia morphine (3 mg every 6 min) was given. Epidural infusions were increased every 30 min by 1 ml/h-1 to achieve a dynamic (during coughing) visual analog pain score (VAPS) of less than 5/10. If the desired VAPS was not achieved after 6 h or the epidural morphine infusion was increased to 2 mg/h-1, 50 micrograms of sufentanil in 10 ml of normal saline was given as an epidural bolus dose. The epidural infusion then was switched to 0.0002% sufentanil (2 micrograms/ml-1) and 0.1% bupivacaine (1 mg/ml-1) at 7 ml/h-1. Further titration to maintain a dynamic VAPS of less than 5/10 occurred every 4 h. RESULTS Mean preoperative daily oral morphine use was 380 +/- 97 mg (range 290-490) for 4 +/- 1 months. Before the switch to sufentanil, patients had received a mean maximum morphine dose of 8.8 +/- 0.2 mg intraoperatively plus 9.0 +/- 1.2 mg during 4.2 +/- 0.3 h postoperatively (1.8 +/- 0.4 mg/h-1), at which point VAPS ranged between 7-10/10. All patients experienced adequate analgesia within 1 h of starting sufentanil therapy. The mean sufentanil dose during the first 4 h of treatment was 17 +/- 0.2 micrograms/h-1. At this time, VAPS ranged from 0-3/10. Satisfactory analgesia was achieved with sufentanil at a lower than a calculated equally potent dose of morphine (23 micrograms/h-1 vs. 17 micrograms/h-1, P < 0.01). Intravenous patient-controlled analgesia morphine requirements were also lower (7.8 mg/h-1 vs. 2.0 mg/h-1, P < 0.01). Length of morphine and sufentanil therapies were 5 +/- 3 h and 10 +/- 2 days, respectively. No patient experienced signs or symptoms of opioid withdrawal. CONCLUSIONS These results suggest that sufentanil can be used successfully in opioid-tolerant patients who do not experience adequate pain control in the early postoperative period despite a large dose of epidural morphine. Moreover, sufentanil should be considered an effective alternative therapy for postoperative pain control in chronic opioid users using high doses of oral opioids before surgical intervention.