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An Opioid Antagonist Improves Postoperative Ileus

After abdominal surgery, opioid receptors in the gastrointestinal (GI) tract are activated -- both by release of endogenous opioids from surgical stress and by opioid drugs given for pain. Because stimulation of these receptors contributes to postoperative ileus, researchers at Washington University in St. Louis examined the effect of receptor inhibition by an orally administered investigational opioid antagonist (ADL 8-2698). This drug is absorbed poorly from the GI tract and does not readily cross the blood-brain barrier. The manufacturer of ADL 8-2698 partially funded this study.

Fifteen patients undergoing partial colectomy and 63 undergoing total abdominal hysterectomy were randomized to ADL 8-2698 (either 1 mg or 6 mg given orally just before surgery and then twice daily until the first bowel movement or hospital discharge) or placebo; all patients received general anesthesia. Compared with placebo recipients, those receiving 6 mg of ADL 8-2698 had significantly shorter median times to passage of flatus (70 vs. 49 hours), first bowel movement (111 vs. 70 hours), and hospital discharge (100 vs. 71 hours). Patients in the 6-mg group also experienced significantly less nausea and vomiting than did placebo recipients. The 1-mg dose was similar to placebo for all endpoints. Postoperative pain and cumulative dose of opioids given for pain relief were similar in the 3 groups.

Comment: Because this investigational opioid antagonist is absorbed poorly from the gastrointestinal tract, it successfully mitigated postoperative ileus without blocking the analgesic effect of opioids such as morphine. An editorialist notes that numerous opioid agonists and antagonists with selective properties currently are being developed.

— AS Brett

Published in Journal Watch General Medicine October 2, 2001

Citation(s):

Taguchi A et al. Selective postoperative inhibition of gastrointestinal opioid receptors. N Engl J Med 2001 Sep 27 345 935-940.

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• Medline abstract (Free)

Steinbrook RA. An opioid antagonist for postoperative ileus. N Engl J Med 2001 Sep 27 345 988-989.

• Original article (Subscription may be required)
• Medline abstract (Free)