Methylnaltrexone Administered Postoperatively to Patients Following Segmental Colectomy Improves Postoperative Ileus Outcome and Hospital Discharge Eligibility without Affecting Opioid Analgesia

Background:

Postoperative ileus (POI) occurs in patients undergoing bowel resection and can lead to prolonged hospitalization. Methylnaltrexone, a quaternary derivative of naltrexone, avoids the peripheral effects of opioids while sparing their central analgesic effects. It is thought that mu‐opioid receptors in the gastrointestinal tract may play a role in the pathogenesis of POI. We hypothesized that methylnaltrexone might improve POI outcome without affecting opioid analgesia.

Methods:

In this double‐blind, randomized, placebo‐controlled study, 65 patients undergoing segmental colectomies via laparotomy were randomized to receive within 90 minutes after surgery either IV methylnaltrexone 0.3 mg/kg every 6 hours or placebo until 24 hours after GI recovery, discharge from the hospital, or for a maximum of 7 days. Time to first bowel movement and discharge eligibility (tolerating solid foods, had at least 1 bowel movement, normal temperature, and no major complications present) were important efficacy outcomes. Postoperative analgesia was provided with systemic opioid analgesics. Adverse events (AEs) were monitored during the study. A signed and dated informed consent form approved by the institutional review board (IRB) was obtained for all patients, and the IRB of each center approved the study.

Results:

The mean time to first bowel movement was accelerated by 20 hours for patients in the methylnaltrexone group compared with those receiving placebo (P = .038). Time to discharge eligibility was also significantly shorter for patients who received methylnaltrexone group than for patients who received placebo (P = .049). Analgesic requirements and pain scores of the methylnaltrexone and placebo patients were similar. AEs, including nausea, vomiting, and abdominal pain, were more frequent in the placebo group than in the methylnaltrexone group. POI, reported as an AE, occurred in 5 subjects in the placebo group (16%) and 2 subjects in the methylnaltrexone group (6%).

Conclusions:

Methylnaltrexone IV accelerates GI recovery and hospital discharge eligibility without affecting opioid analgesia following segmental colectomy. Methylnaltrexone was safe and well tolerated for the management of POI.

Author Disclosure:

J. Rathmell, Progenics Pharmaceuticals, Inc., consulting fees or other remuneration (payment); T. Gan, Progenics Pharmaceuticals, Inc., consulting fees or other remuneration (payment); E. Viscusi, Progenics Pharmaceuticals, Inc., consulting fees or other remuneration (payment); A. Fichera, Progenics Pharmaceuticals, Inc., consulting fees or other remuneration (payment); S. Bin‐derow, Progenics Pharmaceuticals, Inc., consulting fees or other remuneration (payment); N. Stambler, Progenics Pharmaceuticals, Inc., employment (full‐ or part‐time); F. Galasso, Progenics Pharmaceuticals, Inc., employment (full‐ or part‐time); D. Penenberg, Progenics Pharmaceuticals, Inc., employment (full‐ or part‐time); R. Israel, Progenics Pharmaceuticals, Inc., employment (full‐ or part‐time).