SEATTLE (FRONTLINE MEDICAL NEWS) Nonselective NSAIDs increase the risk of anastomotic leaks after colorectal surgery, according to a meta-analysis from the University of Sydney, Australia.

After combing results from six randomized, controlled trials and seven retrospective studies involving a total of 23,508 patients, investigators found that postop nonselective NSAIDs (odds ratio, 0.54; 95% CI, 0.43-0.67; P less than .00001), and especially diclofenac (OR, 0.39; 95% CI, 0.28-0.55; P less than .00001), were both associated with an increased risk of leakage.

There was an increased risk with all NSAIDs compared to patients who did not receive them after surgery, but the risk was statistically significant only for nonselective options like diclofenac on subgroup analysis. There was a trend for increased leakage with the nonselective agent ketorolac, as well, but it was not significant (OR, 0.71; 95% CI, 0.35-1.43; P = .34).

“I’m not going to say we need to wait for more studies; there’s something here. We have to be aware there could be a high risk of leakage with nonsteroidals, and we have to be mindful of that with our ERAS [Enhanced Recovery after Surgery] protocols. I don’t think you should be using nonsteroidals unless you are using them in a trial” and collecting data, “because of the uncertainty,” lead investigator and colorectal surgeon Christopher Young, MD, a clinical associate professor of surgery at the University of Sydney, said at the American Society of Colon and Rectal Surgeons annual meeting.

NSAIDS are a routine part of colorectal ERAS protocols in some places to limit opioid use and hasten recovery and hospital discharge, but there’s been concern for some time that they might also increase the risk of anastomotic leakage. The new Australian findings fit in with previous investigations that raised concerns.

A 2016 review, for instance, found that among 856 patients undergoing an elective colon or rectal resection for cancer, the anastomotic leakage rate was significantly higher in the group that received nonsteroidal anti-inflammatory drugs compared to patients who did not (9.2% versus 5.3%). The higher rate was only seen in patients receiving diclofenac. “The use of diclofenac in colorectal surgery can no longer be recommended. Alternatives for postoperative analgesia need to be explored within an enhanced recovery program,” the investigators concluded (J Gastrointest Surg. 2016 Apr;20[4]:776-82. doi: 10.1007/s11605-015-3010-1 ).

A review of 13,082 bariatric and colorectal surgery patients in Washington State found that NSAIDs beginning within 24 hours after surgery were associated with a 70% increased risk of anastomotic leaks in nonelective colorectal surgery, with a leak rate of 12.3% in the NSAID group and 8.3% in the non-NSAID group (OR, 1.70; 95% CI, 1.11–2.68; P = .01). Although it was unclear which nonsteroidals patients received, intravenous ketorolac or ibuprofen were likely the most common ( JAMA Surg. 2015 Mar 1;150[3]: 223–8 ).

It’s unknown why, exactly, NSAIDs impair healing and anastomotic strength, but it’s thought to be related to effects on prostaglandin synthesis, Dr. Young noted.

Dr. Young had no disclosures.