NSAID administration post colorectal surgery increases anastomotic leak rate: systematic review/meta-analysis

  • Aryan Modasi
  • David Pace
  • Marshall Godwin
  • Chris Smith
  • Bryan Curtis



Current enhanced recovery guidelines suggest that opioid sparing medications should be used for analgesia whenever possible following colorectal surgery. The present study aims to assess whether post-operative NSAID use is associated with an increased anastomotic leak rate after a colonic or rectal anastomosis.


A systematic review was performed for studies investigating anastomotic leak rate following NSAID use vs control after colonic or rectal anastomosis. Meta-analysis was performed to assess for overall risk of anastomotic leak with NSAID use, as well as sub-group analysis to compare selective vs non-selective NSAIDs and drug-specific NSAID safety profiles.


Seven studies were included in the final review. Use of an NSAID post-operatively was associated with an overall increased risk of anastomotic leakage [OR 1.58 (1.23, 2.03), P = 0.0003]. Non-selective NSAIDs were associated with an increased risk [OR 1.79 (1.47, 2.18), P < 0.00001], but selective NSAIDs were not. The non-selective NSAID diclofenac was associated with an increased leak rate [OR 2.79 (1.96, 3.96), P < 0.00001], but ketorolac was not [OR 1.36 (0.89, 2.06), P = 0.16].


Great caution must be taken when prescribing NSAIDs following colonic or rectal anastomotic creation. The safety profile varies within the NSAID class and further research is needed to clarify which NSAIDs are safe for use and which are not.


Early recovery after surgery (ERAS) Non-steroidal anti-inflammatory drugs (NSAIDs) Colorectal anastomosis Anastomotic leak 


Compliance with ethical standards


Drs. Aryan Modasi, David Pace, Marshall Godwin, Chris Smith, and Bryan Curtis have no conflicts of interest or financial ties to disclose.


  1. 1.
    Pang F, Liu S, Hu Y, Yu M, Chen J, Liu C (2016) Influence of perioperative nonsteroidal anti-inflammatory drugs on complications after gastrointestinal surgery: a meta-analysis. Acta Anaesthesiologica Taiwanica 54:121–128CrossRefGoogle Scholar
  2. 2.
    Yauw S, Lomme R, van der Vijver R, Hendriks T, van Laarhoven K, van Goor H (2015) Diclofenac causes anastomotic leakage in the proximal colon but not in the distal colon of the rat. Am J Surg 210(2):382–388CrossRefPubMedGoogle Scholar
  3. 3.
    de Hingh I, van Goor H, de Man B, Lomme R, Bleichrodt R, Hendriks T (2006) Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period. Br J Surg 93(4):489–497CrossRefPubMedGoogle Scholar
  4. 4.
    Van der Vijver R, van Laarhoven C, de Man B, Lomme R, Hendriks T (2013) Perioperative pain relief by a COX-2 inhibitor affects ileal repair and provides a model for anastomotic leakage in the intestine. Surg Innov 20(2):113–118CrossRefPubMedGoogle Scholar
  5. 5.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):1–34CrossRefGoogle Scholar
  6. 6.
    Sterne JAC, Hernán MA, Reeves BC, Savović J et al (2016) ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions. BMJ 355:i4919CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bakker N, Deelder JD, Richir MC, Cakir H, Doodeman HJ, Schreurs WH, Houdijk A (2016) Risk of anastomotic leakage with nonsteroidal anti-inflammatory drugs within an enhanced recovery program. J Gastrointest Surg 20(4):776–782CrossRefPubMedGoogle Scholar
  8. 8.
    Gorissen KJ, Benning D, Berghmans T, Snoeijs MG, Sosef MN, Hulsewe KW, Luyer M (2012) Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery. Br J Surg 99(5):721–727CrossRefPubMedGoogle Scholar
  9. 9.
    Klein M, Andersen LP, Harvald T, Rosenberg J, Gogenur I (2009) Increased risk of anastomotic leakage with diclofenac treatment after laparoscopic colorectal surgery. Dig Surg 26(1):27–30CrossRefPubMedGoogle Scholar
  10. 10.
    Klein M, Gogenur I, Rosenberg J (2012) Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: Cohort study based on prospective data. BMJ 345:e6166. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Paulasir S, Kaoutzanis C, Welch KB, Vandewarker JF, Krapohl G, Lampman RM, Franz M, Cleary R (2015) Nonsteroidal anti-inflammatory drugs: do they increase the risk of anastomotic leaks following colorectal operations? Dis Colon Rectum 58(9):870–877CrossRefPubMedGoogle Scholar
  12. 12.
    Saleh F, Jackson TD, Ambrosini L, Gnanasegaram JJ, Kwong J, Quereshy F, Okrainec A (2014) Perioperative nonselective non-steroidal anti-inflammatory drugs are not associated with anastomotic leakage after colorectal surgery. J Gastrointest Surg 18(8):1398–1404CrossRefPubMedGoogle Scholar
  13. 13.
    Subendran J, Siddiqui N, Victor JC, McLeod RS, Govindarajan A (2014) NSAID use and anastomotic leaks following elective colorectal surgery: a matched case-control study. J Gastrointest Surg 18(8):1391–1397CrossRefPubMedGoogle Scholar
  14. 14.
    Drakopoulou S, Kontis E, Pantiora E, Vezakis A, Karandrea D, Aravidou E, Konti-Paphiti A, Argyra E, Voros D, Polydorou AA, Fragulidis GP (2016) Effects of lornoxicam on anastomotic healing: a randomized, blinded, placebo-control experimental study. Surg Res Pract. PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Klein M, Krarup P, Kongsbak MB, Agren MS, Ggenur I, Jorgensen LN, Rosenberg J (2012) Effect of postoperative diclofenac on anastomotic healing, skin wounds and subcutaneous collagen accumulation: a randomized, blinded, placebo-controlled, experimental study. Eur Surg Res 48(2):73–78CrossRefPubMedGoogle Scholar
  16. 16.
    Haworth R, Oakley K, McCormack N, Pilling A (2005) Differential expression of COX-1 and COX-2 in the gastrointestinal tract of the rat. Toxicol Pathol 33:239–245CrossRefPubMedGoogle Scholar
  17. 17.
    Bhangu A, Singh P, Fitzgerald JE, Slesser A, Tekkis P (2014) Postoperative nonsteroidal anti-inflammatory drugs and risk of anastomotic leak: meta-analysis of clinical and experimental studies. World J Surg 38(9):2247–2257CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of General SurgeryMemorial University of NewfoundlandSt. John’sCanada
  2. 2.Department of Family Medicine and Clinical EpidemiologyMemorial University of NewfoundlandSt. John’sCanada
  3. 3.Department of Nephrology and Clinical EpidemiologyMemorial University of NewfoundlandSt. John’sCanada

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