title: Gastrointestinal tract recovery in patients undergoing bowel resection: results of a randomized trial of alvimopan and placebo with a standardized accelerated postoperative care pathway.
abstract: OBJECTIVE
  To investigate the efficacy and safety of alvimopan, 12 mg, administered orally 30 to 90 minutes preoperatively and twice daily postoperatively in conjunction with a standardized accelerated postoperative care pathway for managing postoperative ileus after bowel resection.
  
  
  METHODS
  This multicenter, randomized, placebo-controlled, double-blind, phase 3 trial enrolled adult patients undergoing partial bowel resection with primary anastomosis by laparotomy and scheduled to receive intravenous, opioid-based, patient-controlled analgesia. A standardized accelerated postoperative care pathway including early ambulation, oral feeding, and postoperative nasogastric tube removal was used to facilitate gastrointestinal (GI) tract recovery in all of the patients.
  
  
  METHODS
  The primary end point was time to GI-2 recovery (toleration of solid food and first bowel movement). Secondary end points included time to GI-3 recovery (toleration of solid food and first flatus or bowel movement), hospital discharge order written, and actual hospital discharge. Postoperative length of hospital stay based on calendar day of hospital discharge order written, opioid consumption, and overall postoperative ileus-related morbidity were recorded.
  
  
  RESULTS
  Alvimopan, 12 mg, was well tolerated and significantly accelerated GI-2 recovery, GI-3 recovery, and actual hospital discharge compared with a standardized accelerated postoperative care pathway alone (hazard ratio = 1.5, 1.5, and 1.4, respectively; P < .001 for all). Time to hospital discharge order written as measured by hazard ratio (1.4) and by postoperative calendar days (mean for alvimopan, 5.2 days; mean for placebo, 6.2 days) was also accelerated. Opioid consumption was comparable between groups, and alvimopan was associated with reduced postoperative ileus-related morbidity compared with placebo.
  
  
  CONCLUSIONS
  Alvimopan, 12 mg, administered 30 to 90 minutes before and twice daily after bowel resection is well tolerated, accelerates GI tract recovery, and reduces postoperative ileus-related morbidity without compromising opioid analgesia.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA. kludwig@mcw.edu
authors.forename: Kirk
authors.initials: K
authors.lastname: Ludwig
authors.forename: Warren E
authors.initials: WE
authors.lastname: Enker
authors.forename: Conor P
authors.initials: CP
authors.lastname: Delaney
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Wolff
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: John G
authors.initials: JG
authors.lastname: Fort
authors.forename: Maryann
authors.initials: M
authors.lastname: Cherubini
authors.forename: James
authors.initials: J
authors.lastname: Cucinotta
authors.forename: Lee
authors.initials: L
authors.lastname: Techner
mesh_terms: D000328:Adult; D019091:Critical Pathways; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D045823:Ileus / Q000188:drug therapy*; D007422:Intestines / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011182:Postoperative Care; D011183:Postoperative Complications; D020127:Recovery of Function; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; C419502:alvimopan