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 2012; 345 doi: https://doi.org/10.1136/bmj.e6166 (Published 26 September 2012) Cite this as: BMJ 2012;345:e6166
- Mads Klein, research fellow,
- Ismail Gögenur, senior resident,
- Jacob Rosenberg, professor and chief surgeon
- Correspondence to: M Klein madsklein1{at}gmail.com
- Accepted 24 August 2012
Abstract
Objectives To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection.
Design Cohort study based on data from a prospective clinical database and electronically registered medical records.
Setting Six major colorectal centres in eastern Denmark.
Participants 2766 patients (1441 (52%) men) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009. Median age was 70 years (interquartile range 62-77).
Intervention Postoperative use of NSAID (defined as at least two days of NSAID treatment in the first seven days after surgery).
Main outcome measures Frequency of clinical anastomotic leakage verified at reoperation; mortality at 30 days.
Results Of 2756 patients with available data and included in the final analysis, 1871 (68%) did not receive postoperative NSAID treatment (controls) and 885 (32%) did. In the NSAID group, 655 (74%) patients received ibuprofen and 226 (26%) received diclofenac. Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment, compared with controls (12.8% and 8.2% v 5.1%; P<0.001). After unadjusted analyses and when compared with controls, more patients had anastomotic leakage after treatment with diclofenac (7.8% (95% confidence interval 3.9% to 12.8%)) and ibuprofen (3.2% (1.0% to 5.7%)). But after multivariate logistic regression analysis, only diclofenac treatment was a risk factor for leakage (odds ratio 7.2 (95% confidence interval 3.8 to 13.4), P<0.001; ibuprofen 1.5 (0.8 to 2.9), P=0.18). Other risk factors for anastomotic leakage were male sex, rectal (v colonic) anastomosis, and blood transfusion. 30 day mortality was comparable in the three groups (diclofenac 1.8% v ibuprofen 4.1% v controls 3.2%; P=0.20).
Conclusions Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery. Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis. Large scale, randomised controlled trials are urgently needed.
Footnotes
We thank medical students Anne Sofie Bisgård and Morten Noack Christensen from the University of Copenhagen for their invaluable help in registering postoperative medicine consumption; statistical consultant Tobias Wirenfeldt Klausen, from Herlev Hospital, University of Copenhagen, for his assistance with data analysis; and the Danish Colorectal Cancer Group for delivering data.
Contributors: MK was responsible for the study conception and design; acquisition, analysis and interpretation of data; manuscript drafting and revision; and is the study guarantor. IG and JR were responsible for the study conception and design, critical manuscript revision and approval, supervision, and administrative support. All authors have had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: This study received no direct funding. The authors were personally salaried by their institutions during the period of writing (although no specific salary was set aside or given for the writing of this paper). No funders had any role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study was approved by the Scientific Council of the Danish Colorectal Cancer Group and by the Danish Data Protection Agency before initiation (J 2008-41-2484). According to Danish law, because of the study design with no patient contact and not involving biological material, ethical committee approval should not be obtained for this type of study.
Data sharing: Dataset and multivariate analyses examining risk factors for all cause mortality at 30 days are available from the corresponding author at madsklein1@gmail.com.
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