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Systematic Review and Meta-analysis of Nonsteroidal Anti-inflammatory Drugs to Improve GI Recovery After Colorectal Surgery

Chapman, Stephen J., M.R.C.S. (Eng.)1; Garner, Joesph J., B.Sc. (Hons.)2; Drake, Thomas M., M.B.Ch.B.3; Aldaffaa, Mohammed2; Jayne, David G., F.R.C.S.1

doi: 10.1097/DCR.0000000000001281
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BACKGROUND: The management of delayed GI recovery after surgery is an unmet challenge. Uncertainty over its pathophysiology has limited previous research, but recent evidence identifies intestinal inflammation and activation of µ-opioid receptors as key mechanisms. Nonsteroidal anti-inflammatory drugs are recommended by enhanced recovery protocols for their opioid-sparing and anti-inflammatory properties.

OBJECTIVES: The purpose of this study was to explore the safety and efficacy of nonsteroidal anti-inflammatory drugs to improve GI recovery and to identify opportunities for future research.

DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were systematically searched from inception up to January 2018.

STUDY SELECTION: Randomized controlled trials assessing the effect of nonsteroidal anti-inflammatory drugs on GI recovery after elective colorectal surgery were eligible.

MAIN OUTCOME MEASURES: Postoperative GI recovery, including first passage of flatus, stool, and oral tolerance, were measured.

RESULTS: Six randomized controlled trials involving 563 participants were identified. All of the participants received patient-controlled morphine and either nonsteroidal anti-inflammatory drug (nonselective: n = 4; cyclooxygenase-2 selective: n = 1; either: n = 1) or placebo. Patients receiving the active drug had faster return of flatus (mean difference: –17.73 h (95% CI, –21.26 to –14.19 h); p < 0.001), stool (–9.52 h (95% CI, –14.74 to –4.79 h); p < 0.001), and oral tolerance (–12.00 h (95% CI, –18.01 to –5.99 h); p < 0.001). Morphine consumption was reduced in the active groups of 4 studies (average reduction, 12.9–30.0 mg), and 1 study demonstrated significantly reduced measures of systemic inflammation. Nonsteroidal anti-inflammatory drugs were not associated with adverse events, but 1 study was temporarily suspended for safety.

LIMITATIONS: The data presented are relatively outdated but represent the best available evidence.

CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may represent an effective and accessible intervention to improve GI recovery, but hesitancy over their use after colorectal surgery persists. Additional preclinical research to characterize their mechanisms of action, followed by well-designed clinical studies to test safety and patient-reported efficacy, should be considered.

1 Section of Translational Anaesthesia and Surgery, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom

2 Leeds School of Medicine, University of Leeds, Leeds, United Kingdom

3 Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom

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Funding/Support: S.J.C. is supported by the National Institute for Health Research (NIHR) Academic Clinical Fellowship programme. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

Financial Disclosure: None reported.

Presented at the meeting of The Association of Coloproctology of Great Britain and Ireland, Birmingham, United Kingdom, July 9 to 11, 2018.

Correspondence: Stephen J. Chapman, M.R.C.S. (Eng.), Section of Translational Anaesthesia and Surgery, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, United Kingdom LS9 7TF. E-mail:; Twitter: @SJ_Chapman; ORCID:

© 2019 The American Society of Colon and Rectal Surgeons