Risk of anastomotic leakage with use of NSAIDs after gastrointestinal surgery

Analgesic regimes to avoid opioid-related adverse effects have been recommended in gastrointestinal surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important component of opioid sparing regimes in that these drugs indirectly reduce pain by inhibiting inflammation. Although beneficial for most surgical patients, animal studies and recent clinical studies suggest a harmful effect on new intestinal anastomoses by increasing the rate of leakage. NSAIDs may indirectly disturb anastomotic healing by inhibiting inflammation as an integrated part of the wound healing process in an early, critical phase after surgery.

A literature review based on a structured search in PubMed of clinical and experimental studies investigating the effects of NSAIDs on anastomotic healing and leakage rates after intestinal surgery, as well as proposed mechanisms and effects studied in animal models.

Three recent observational cohort studies (accumulated n = 882) indicate an increased rate of anastomotic leakages (15-21%) associated with cyclooxygenase-2 (COX-2) selective NSAIDs after intestinal surgery compared to the leakage rates in controls or historical cohorts (1-4%). Three prospective studies on related topics contain relevant data on NSAIDs and are compared to these studies. Several experimental animal studies support an increased risk for anastomotic leakage with the use of NSAIDs.

The reported effects of NSAIDs on anastomotic healing suggest an increased risk for leakage. A better understanding of the complex interactions of NSAID-induced inhibition on anastomotic healing is a prerequisite for the safe use of NSAIDs. Until more data are available, a careful use of NSAIDs may be warranted in gastrointestinal anastomotic surgery.