Methylnaltrexone May Improve Postoperative Ileus After Segmental Colectomy

May 25, 2007 — Methylnaltrexone given postoperatively after segmental colectomy improved postoperative ileus and other outcomes, according to a presentation today at the Hospital Medicine 2007: Society for Hospital Medicine annual meeting in Dallas, Texas.

"Methylnaltrexone following segmental colectomy appears to accelerate gastrointestinal recovery and hospital discharge without affecting opioid analgesia," presenter and lead author James P. Rathmell, MD, director of the Massachusetts General Hospital Pain Center and an associate professor of anaesthesia at Harvard Medical School in Boston, Massachusetts, told Medscape. "Methylnaltrexone was safe and well tolerated."

Postoperative ileus following bowel resection can prolong hospitalization, most likely via a mechanism of action involving µ-opioid receptors in the gastrointestinal tract. Methylnaltrexone, a quaternary derivative of naltrexone, can avoid the peripheral effects of opioids while sparing the central analgesia effects.

"This was a well-conducted study by a very reputable group," Neil Hyman, MD, chief of general surgery and a professor of surgery at the University of Vermont College of Medicine, told Medscape. Dr. Hyman was not involved in this study but was asked to provide independent commentary. "The key is that the improvement in time to first bowel movement was 20 hours."

In this double-blind, randomized, placebo-controlled study, 65 patients undergoing laparotomy for segmental colectomy were randomized to receive (within 90 minutes after surgery) either intravenous methylnaltrexone, 0.3 mg/kg every 6 hours, or placebo, until 24 hours after gastrointestinal recovery, discharge from the hospital, or for a maximum of 7 days. Systemic opioid analgesics were used for postoperative analgesia.

Efficacy endpoints were time to first bowel movement and discharge eligibility, defined as tolerating solid foods, having had at least 1 bowel movement, normal temperature, and no major complications. Adverse events were monitored during the study, and all patients gave informed consent.

Compared with patients receiving placebo, those in the methylnaltrexone group had a shorter mean time to first bowel movement by 20 hours (P = .038) and a shorter time to discharge eligibility (P = .049).

"Ileus is a very complicated phenomenon that has many aspects," Dr. Hyman says. "The opiate-related aspect that methylnaltrexone can reverse is just part of it, so therefore one would only predict some improvement in the duration of ileus. Clearly methylnaltrexone is not a magic bullet, nor would we expect it to be, but there is a clinically meaningful improvement in duration of ileus."

Both groups had similar analgesic requirements and pain scores. Adverse events, including nausea, vomiting, and abdominal pain, were more frequent in the placebo group than in the methylnaltrexone group. Hypotension occurred in 3 patients in the placebo group and 6 patients in the methylnaltrexone group, but this difference was not statistically significant.

"Methylnaltrexone may have wide applications in reducing the frequency, severity, and duration of postoperative ileus by producing selective peripheral antagonism of opioid-related side-effects on the bowel," Dr. Rathmell says. "This may translate into faster recovery with less nausea and vomiting and earlier ability to resume a normal diet after surgery."

However, Dr. Rathmell notes that this was a limited study showing that the drug is safe and seems to reduce the duration of ileus. Larger studies are needed to prove this effect and to establish the best dosing regimen for the drug. Because this study was limited to patients undergoing colectomy, methylnaltrexone must be tested in other types of surgery.

"Compared with placebo, there were no statistically significant increases in adverse events in the methylnaltrexone group, but there were twice as many incidents of hypotension," Dr. Hyman notes. "The potential for unpredicted cardiovascular events with methylnaltrexone is something that would bear watching."

Dr. Rathmell and several other authors have disclosed various financial relationships with Progenics Pharmaceuticals, Inc., which also funded this study and employs 4 other authors. Dr. Hyman has disclosed no financial relationships.

Hospital Medicine 2007: Abstract 51. Presented May 25, 2007.

Source: http://www.medscape.com/viewarticle/557266?src=mp