Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery

Gorissen, K.; Benning, D; Berghmans, Thierry; Snoeijs, Maarten G.; Sosef, Meindert N.; Hulsewé, Karel W. E.; Luyer, Misha

doi:10.1002/bjs.8691

Cited by 187 publications

(111 citation statements)

References 36 publications

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“…However, considering the physiological changes that occur following partial or subtotal colectomy, bile toxicity could be comparably relevant for colorectal anastomoses. Clinical cohort studies2, 3, 4 8 reporting an increased risk of leakage following NSAID administration involved both ileocolic and colorectal anastomoses.…”

Section: Discussionmentioning

confidence: 99%

“…Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been related to increased leak rates in both animal and retrospective human studies2, 3, 4. This is worrisome because NSAIDs are recommended as postoperative analgesics in current guidelines5.…”

Section: Introductionmentioning

confidence: 99%

“…The main mechanism by which NSAIDs are believed to jeopardize anastomotic healing is the cyclo‐oxygenase (COX) 2 inhibitory action, which may cause suppression of inflammatory, proliferative or proangiogenic pathways relevant for normal wound healing2 8. An alternative explanation could be direct toxicity of intraluminal factors resulting from NSAID treatment (such as drug metabolites and bile products).…”

Section: Introductionmentioning

confidence: 99%

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Experimental study of diclofenac and its biliary metabolites on anastomotic healing

et al. 2018

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BackgroundDiclofenac increases the risk of anastomotic leakage, but the underlying mechanism is unknown. As diclofenac is excreted largely as biliary metabolites, the aim of this study was to determine the effect of these metabolites on intestinal anastomoses.MethodsThis was a randomized controlled blinded experiment using 210 male Wistar rats to assess the effect of ‘diclofenac bile’ on the anastomotic complication score, leak rate and anastomotic strength following oral and parenteral administration of diclofenac. Bile duct and duodenal catheterization techniques were used for diversion and replacement of bile, and biliary diclofenac metabolites were determined.ResultsReplacement of control bile with diclofenac bile resulted in higher anastomotic complication scores (P = 0·006) and leakage in five of 18 animals, compared with one of 18 controls (P = 0·089). In turn, following oral diclofenac administration, replacement of diclofenac bile with control bile reduced anastomotic complications (P = 0·016). The leak rate was seven of 15 versus 13 of 17 without replacement (P = 0·127). After intramuscular administration of diclofenac, the reduction in anastomotic complications was not significant when bile was replaced with control bile (P = 0·283), but it was significant when bile was drained without replacement (P = 0·025). Diclofenac metabolites in bile peaked within 2 h after administration. Administration of diclofenac bile resulted in nearly undetectable plasma levels of diclofenac (mean(s.d.) 0·01(0·01) μg/ml) after 120 min. Following oral diclofenac, bile replacement with control bile did not affect the plasma concentration of diclofenac (0·12(0·08) μg/ml versus 0·10(0·05) μg/ml with diclofenac bile; P = 0·869).ConclusionAltered bile composition as a result of diclofenac administration increases the ileal anastomotic complication rate in rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Experimental study of diclofenac and its biliary metabolites on anastomotic healing

et al. 2018

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“…We read with interest the recent article by Gorissen et al [1] from the Netherlands reporting data from two teaching hospitals concerning use of non-steroidal anti-inflammatory drugs (NSAIDs) and anastomotic leakage in colorectal surgery.…”

Section: Commentary On Hot Articlesmentioning

confidence: 99%

“…In the present article, Gorissen et al [1] analyzed retrospectively 795 patients who underwent primary colorectal anastomosis during a three-year period from 2008 to 2010 at two Dutch teaching hospitals. Indications for surgery included both benign disease and colorectal malignancy, and elective as well as emergency surgery was performed.…”

Section: Commentary On Hot Articlesmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

Rutegård

Rutegård²

2012

WJGS

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In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.

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Nonsteroidal Anti-inflammatory Drugs and the Risk for Anastomotic Failure

et al. 2015

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IMPORTANCE Nonsteroidal anti-inflammatory drugs (NSAIDs) have many physiologic effects and are being used more commonly to treat postoperative pain, but recent small studies have suggested that NSAIDs may impair anastomotic healing in the gastrointestinal tract. OBJECTIVE To evaluate the relationship between postoperative NSAID administration and anastomotic complications. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 13 082 patients undergoing bariatric or colorectal surgery at 47 hospitals in Washington State from January 1, 2006, through December 31, 2010, using data from the Surgical Care and Outcomes Assessment Program linked to the Washington State Comprehensive Abstract Reporting System. EXPOSURE NSAID administration beginning within 24 hours after surgery. MAIN OUTCOMES AND MEASURES We used multivariate logistic regression modeling to assess the risk for anastomotic complications (reoperation, rescue stoma, revision of an anastomosis, and percutaneous drainage of an abscess) through 90 days after bariatric and colorectal surgery involving anastomoses. RESULTS Of the 13 082 patients (mean [SD] age, 58.1 [15.8] years; 60.7% women), 3158 (24.1%) received NSAIDs. The overall 90-day rate of anastomotic leaks was 4.3% for all patients (151 patients [4.8%] in the NSAID group and 417 patients [4.2%] in the non-NSAID group; P = .16). After risk adjustment, NSAIDs were associated with a 24% increased risk for anastomotic leak (odds ratio, 1.24 [95% CI, 1.01–1.56]; P = .04). This association was isolated to nonelective colorectal surgery, for which the leak rate was 12.3% in the NSAID group and 8.3% in the non-NSAID group (odds ratio, 1.70 [95% CI, 1.11–2.68]; P = .01). CONCLUSIONS AND RELEVANCE Postoperative NSAIDs were associated with a significantly increased risk for anastomotic complications among patients undergoing nonelective colorectal resection. To determine the role of NSAIDs in colorectal surgery, future evaluations should consider specific formulations, the dose effect, mechanism, and other relevant outcome domains, including pain control, cardiac complications, and overall recovery.

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Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery

Abstract: Non-selective NSAIDs may be associated with anastomotic leakage.

Cited by 187 publications

References 36 publications

Experimental study of diclofenac and its biliary metabolites on anastomotic healing

Experimental study of diclofenac and its biliary metabolites on anastomotic healing

Non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

Nonsteroidal Anti-inflammatory Drugs and the Risk for Anastomotic Failure

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