title: Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus.
abstract: OBJECTIVE
  This phase 2 study evaluated the safety and activity of intravenous methylnaltrexone on the duration of postoperative ileus in patients undergoing segmental colectomy.
  
  
  METHODS
  Adults (aged 18 years or older) with American Society of Anesthesiologists physical status of I, II, or III who underwent segmental colectomy, including partial colectomy, sigmoidectomy, cecectomy, or anterior proctosigmoidectomy, via laparotomy with general anesthesia, received intravenous methylnaltrexone 0.30 mg/kg or placebo every 6 h beginning within 90 min after end of surgery. Treatment continued until 24 h after the patient tolerated solid foods, was discharged, or for 7 d maximum. Efficacy endpoints included measures of gastrointestinal recovery and time to discharge eligibility.
  
  
  RESULTS
  A total of 65 patients (methylnaltrexone, n = 33; placebo, n = 32) were randomized. Mean time to first bowel movement was accelerated by 20 h (p = 0.038) and time to discharge eligibility was accelerated by 33 h (p = 0.049) with methylnaltrexone vs placebo. Opioid use was similar between groups until postoperative day 4, then fluctuated in the placebo group. Methylnaltrexone was generally well tolerated.
  
  
  CONCLUSIONS
  In this study, intravenous methylnaltrexone significantly decreased time to postoperative bowel recovery and eligibility for hospital discharge by ∼1 d, with an adverse event profile similar to placebo. These were two of several exploratory endpoints; not all efficacy endpoints showed a significant difference between methylnaltrexone and placebo. The efficacy results in this trial were not seen in two subsequent large-scale studies.
authors.affiliation: Thomas Jefferson University, Philadelphia, PAUSA.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Viscusi
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MAUSA.
authors.forename: James P
authors.initials: JP
authors.lastname: Rathmell
authors.affiliation: University of Chicago, Chicago, ILUSA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fichera
authors.affiliation: Atlanta Colon and Rectal Surgery, Atlanta, GAUSA.
authors.forename: Sander R
authors.initials: SR
authors.lastname: Binderow
authors.affiliation: Progenics Pharmaceuticals, Inc., Tarrytown, NYUSA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Israel
authors.affiliation: Progenics Pharmaceuticals, Inc., Tarrytown, NYUSA.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Galasso
authors.affiliation: Progenics Pharmaceuticals, Inc., Tarrytown, NYUSA.
authors.forename: Darryl
authors.initials: D
authors.lastname: Penenberg
authors.affiliation: Duke University Medical Center, Durham, NCUSA.
authors.forename: Tong J
authors.initials: TJ
authors.lastname: Gan
keywords: Methylnaltrexone; Mu-opioid receptor antagonist; Opioids; Postoperative ileus