Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors
Akiko Taguchi, M.D., Neeru Sharma, M.D., Rao M. Saleem, M.D., Daniel I. Sessler, M.D., Randall L. Carpenter, M.D., Mahmoud Seyedsadr, Ph.D., and Andrea Kurz, M.D.
Background Postoperative recovery of gastrointestinal functionand resumption of oral intake are critical determinants of thelength of hospital stay. Although opioids are effective treatmentsfor postoperative pain, they contribute to the delayed recoveryof gastrointestinal function.
Methods We studied the effects of ADL 8-2698, an investigationalopioid antagonist with limited oral absorption that does notreadily cross the blood–brain barrier, on postoperativegastrointestinal function and the length of hospitalization.We randomly assigned 79 patients — including 1 whose surgerywas canceled — to receive one capsule containing 1 mgor 6 mg of ADL 8-2698 or an identical-appearing placebo capsuletwo hours before major abdominal surgery and then twice dailyuntil the first bowel movement or until discharge from the hospital.Data were analyzed for 26 patients in each of the three groups;all received opioids for postoperative pain relief. Observerswho were unaware of the group assignments evaluated the outcomes.
Results Fifteen patients underwent partial colectomy and 63underwent total abdominal hysterectomy. Patients given 6 mgof ADL 8-2698 had significantly faster recovery of gastrointestinalfunction than those given placebo. The median time to the firstpassage of flatus decreased from 70 to 49 hours (P=0.03), themedian time to the first bowel movement decreased from 111 to70 hours (P=0.01), and the median time until patients were readyfor discharge decreased from 91 to 68 hours (P=0.03). Effectsin the group that received 1 mg of ADL 8-2698 were less pronounced.
Conclusions Selective inhibition of gastrointestinal opioidreceptors by an antagonist with limited oral absorption thatdoes not readily cross the blood–brain barrier speedsrecovery of bowel function and shortens the duration of hospitalization.
Source Information
From the Department of Anesthesiology, Washington University, St. Louis (A.T., N.S., R.M.S., A.K.); the Outcomes Research Institute and the Department of Anesthesiology, University of Louisville, Louisville, Ky. (D.I.S.); the Department of Anesthesia and General Intensive Care, University of Vienna, Vienna, Austria (D.I.S., A.K.); and Adolor, Exton, Pa. (R.L.C., M.S.).
Address reprint requests to Dr. Kurz at the Department of Anesthesiology, Washington University, 660 S. Euclid Ave., St. Louis, MO 63110, or at kurza{at}msnotes.wustl.edu.
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