Diclofenac increases risk for anastomotic leakage after colorectal surgery

The use of cyclo-oxygenase (COX)-2 nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for anastomotic leakage after colorectal surgery, research shows.

Treatment with diclofenac was associated with a more than sevenfold increased risk for leakage in colon cancer patients undergoing surgery with colorectal resection.

However, use of the COX-1 selective NSAID ibuprofen did not increase the risk for leakage.

"COX-2 selective NSAIDs should be used with caution after colorectal resection and primary anastomosis," report Mads Klein (University of Copenhagen, Denmark) and colleagues in the British Medical Journal.

Leakage rates are typically 3% after colonic resection and 10% after rectal resections, making the matter "a serious challenge for colorectal surgeons worldwide," explain the researchers.

NSAIDs are frequently used in postoperative analgesic treatment regimens, and are currently part of the recommended treatment following colorectal resection.

"Our results could therefore have an important effect on daily clinical practice," state Klein and colleagues.

The present analysis included 2766 patients undergoing elective surgery for colorectal cancer with colonic/rectal resection and primary anastomosis between 2006 and 2009.

Anastomotic leakage requiring reoperation was confirmed in 12.8% of 226 patients treated with diclofenac. By contrast, leakage occurred in 8.2% of 655 patients treated with ibuprofen and 5.1% of 1871 patients who did not receive postoperative NSAID treatment.

In multivariate analysis, the use of diclofenac, but not ibuprofen, was associated with a significantly increased risk for anastomotic leakage (odds ratio=7.2).

In addition to diclofenac treatment, male gender, intraoperative transfusion, the hospital where the surgery was performed, and rectal anastomosis compared with colonic anastomosis were also associated with an increased risk for leakage.

The analysis revealed no significant differences in the rates of 30-day mortality among patients in the control-, diclofenac-, and ibuprofen- treatment arms. Mortality following anastomotic leakage also did not vary between the groups.

The researchers conclude that large-scale clinical trials are needed to address the leakage risk associated with COX-2 selective NSAIDs in colorectal resection. To identify a decrease in risk for 30% of anastomotic leakage, such a trial would require 2100 patients in each treatment arm, they note.

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