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New Drug Helps Bowels Get a Move On

Morphine-blocker speeds recovery for abdominal surgery patients

WEDNESDAY, Sept. 26, 2001 (HealthDayNews) -- A drug that eases the paralyzing grip of powerful painkillers on the bowels can significantly speed recovery after major abdominal surgery, a new study says.

The experimental compound, called ADL 8-2698, hastens the passage of gas after surgery -- a welcome sign the bowels are getting back to normal -- quickens the time to the first bowel movement, and shortens hospital stays by about a day, researchers say. It also may be useful in treating bowel problems caused by long-term treatments with narcotics, particularly morphine, for other conditions, experts say.

The findings appear this week in The New England Journal of Medicine.

The bowels are notoriously sensitive to surgical procedures, easily falling into a state known as ileus -- an impaired ability to move spontaneously. "Almost any time the surgeon opens the belly and looks at the bowels, they stop moving," says Dr. Richard Steinbrook, a Harvard University anesthesiologist who calls intestinal balkiness "a major surgical issue."

Complicating the trauma of surgery, morphine and other narcotics clamp down on intestinal movement like a chemical vice, causing discomfort, nausea and vomiting that keep surgery patients in the hospital or make life generally miserable for those who take the drugs chronically.

ADL 8-2698 is an opioid antagonist that dulls the effects of drugs like morphine on the cells in the gut. However, since it doesn't cross the blood-brain barrier -- a defense system that protects the brain -- it doesn't dull their painkilling properties. "This drug is not antagonizing the analgesic effects of the morphine; the analgesic effects of morphine are central and happening in the brain," says study co-author Dr. Andrea Kurz, an anesthesiologist at Washington University in St. Louis.

The compound is made by Adolor Corp. of Exton, Pa., which helped sponsor the trial along with the National Institutes of Health and other groups.

Kurz and her colleagues compared ADL 8-2698 and a dummy pill in 78 patients; 15 were undergoing partial colon removal and 63 were having their uteruses removed.

Two hours before their operation, patients took either 1 milligram or 6 milligrams of ADL 8-2698 or a placebo and were treated for pain with conventional opioids, such as morphine.

Neither dose of the experimental drug made the pain worse after the operation. Yet the 6-milligram pill cut the average time to the first passing of gas from 70 hours to 49 hours, and the time to a first bowel movement from 111 hours to 70 hours. The drug also trimmed the time patients were ready to leave the hospital from 91 to 68 hours, a difference of 23 hours, or nearly a full day.

Kurz says the drug worked surprisingly well. "In terms of the main outcomes -- flatus [passing of gas], return of bowel function and fitness at time of discharge -- it actually performed extremely well," says Kurz.

Since the study only looked at colon surgery and hysterectomy, it's not certain ADL 8-2698 would work equally well for patients who've undergone other operations. Kurz believes it would, but notes that since gastric procedures have the double impact of irritating the intestines and bathing the gut with morphine, the drug's best results are likely to involve these patients.

Officials at Adolor could not be reached for comment about their plans for the compound.

Steinbrook, author of an editorial accompanying the journal article, says if the new drug could improve recovery times, it would be an important advance for patients and a money-saving step, as well. One study released about a decade ago found that the cost of post-surgery ileus nationwide was roughly $750 million, a price that could be reduced by about 20 percent to 25 percent if hospital stays were shortened by 24 hours or so, Steinbrook says.

What To Do: For more on gastric illnesses and conditions, visit the American College of Gastroenterology. To learn more about operations, try YourSurgery.

SOURCES: Interviews with Andrea Kurz, M.D., assistant professor of anesthesiology, Washington University, St. Louis, and Richard Steinbrook, M.D., associate professor of anesthesia, Harvard Medical School, director of clinical research, Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Boston; Sept. 27, 2001, The New England Journal of Medicine
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