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.
Main outcome measures
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.
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Neither author has any conflicts of interest to declare. This study was unfunded. This work was undertaken by one of the authors (TD) during a period of research funded by the Royal College of Surgeons of Edinburgh and the Pathological Society. Both authors contributed equally in the study conception, analysis and drafting of the final manuscript. Both TD and AW approved the final manuscript version prior to submission.
Conflict of Interest
TD has received research funding from the Royal College of Surgeons of Edinburgh, The Pathological Society, The Institute of Medical Ethics, The British Medical Association, The Wellcome Trust/Academy of Medical Sciences and The Bowel Disease Research Fund. Neither individual owns stocks and shares in any company related to this article. Neither individual owns any patents related to this article.
This study was unfunded. The preparation of this manuscript was unfunded. Initial data analyses were undertaken by TD and AW.
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Drake, T.M., Ward, A.E. Pharmacological management to prevent ileus in major abdominal surgery: a systematic review and meta-analysis. J Gastrointest Surg 20, 1253–1264 (2016). https://doi.org/10.1007/s11605-016-3140-0
- Postoperative complications
- Postoperative care
- Digestive system surgery
- Opioid antagonists
- Serotonin receptor