title: Pharmacological management to prevent ileus in major abdominal surgery: a systematic review and meta-analysis.
abstract: Prolonged ileus is a common complication following gastrointestinal surgery, with an incidence of up to 40 %. Investigations examining pharmacological treatment of ileus have proved largely disappointing; however, recently, several compounds have been shown to have benefited when used as prophylaxis to prevent ileus.
  
  
  
  This review aimed to evaluate the safety and efficacy of compounds which have been recently developed or repurposed to reduce bowel recovery time, thereby preventing ileus.
  
  
  
  Data were taken from a systematic review of the MEDLINE, EMBASE and Cochrane Library Databases, in addition to manual searching of reference lists up to April 2015. No limits were applied.
  
  
  
  Only randomized trials were eligible for inclusion.
  
  
  
  Opioid receptor antagonists, ghrelin receptor agonists and serotonin receptor agonists used for the prevention of postoperative ileus in gastrointestinal surgery.
  
  
  
  Outcomes of time to first defecation, first flatus and composite bowel recovery endpoints (GI2 and GI3) were used to determine efficacy. Pooled treatment effects were presented as the standard mean difference or as hazard ratios alongside the corresponding 95 % confidence intervals. Risk of bias was assessed using the Cochrane risk of bias framework.
  
  
  
  A total of 17 studies were included in the final analysis. The μ-opioid receptor antagonist alvimopan and serotonin receptor agonists appeared to significantly shorten the duration of ileus. The use of Ghrelin receptor agonists did not appear to have any effect in five trials. No publication bias was detected.
  
  
  
  Most of the trials were poorly reported and of mixed quality. Future studies must focus on the development of a set of core outcomes.
  
  
  
  There is evidence to make a strong recommendation for the use of alvimopan in major gastrointestinal surgery to reduce postoperative ileus. Further randomized trials are required to establish whether serotonin receptor agonists are of use. Identifying a low-cost compound to promote bowel recovery following surgery could reduce complications and shorten duration of hospital admissions.
authors.affiliation: Academic Unit of Surgical Oncology, The Medical School, University of Sheffield, Sheffield, S10 2RX, UK. TMDrake1@sheffield.ac.uk.|Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK. TMDrake1@sheffield.ac.uk.
authors.forename: T M
authors.initials: TM
authors.lastname: Drake
authors.affiliation: Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2JF, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Ward
mesh_terms: D000005:Abdomen / Q000601:surgery; D013505:Digestive System Surgical Procedures; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D045823:Ileus / Q000209:etiology / Q000517:prevention & control*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D009292:Narcotic Antagonists; D010880:Piperidines; D054440:Receptors, Ghrelin; D017366:Serotonin Receptor Agonists; C419502:alvimopan
keywords: Digestive system surgery; Ileus; Opioid antagonists; Postoperative care; Postoperative complications; Serotonin receptor