Carprofen for perioperative analgesia causes early anastomotic leakage in the rat ileum

Abstract

BackgroundThere is increasing evidence that perioperative use of NSAIDs may compromise the integrity of intestinal anastomoses. This study aims to characterize the negative effects of carprofen on early anastomotic healing in the rat ileum.ResultsIn 159 male Wistar rats an anastomosis was constructed in the ileum. In experiment 1 eighty-four rats were divided over control and experimental groups, which received daily buprenorphine or carprofen, respectively, as an analgesic and were killed on day 1, 2 or 3 after surgery. In experiment 2 three groups of 15 rats received carprofen either immediately after surgery or with a delay of 1 or 2 days. Animals were killed after 3 days of carprofen administration. In experiment 3 three groups of 10 rats received different doses (full, half or quarter) of carprofen from surgery.In significant contrast to buprenorphine, which never did so, carprofen induced frequent signs of anastomotic leakage, which were already present at day 1. If first administration was delayed for 48 hours, the leakage rate was significantly reduced (from 80 to 20%; p = 0.0028). Throughout the study, the anastomotic bursting pressure was lowest in animals who displayed signs of anastomotic leakage. Loss of anastomotic integrity did not coincide with reduced levels of hydroxyproline or increased activity of matrix metalloproteinases.ConclusionsCarprofen interferes with wound healing in the rat ileum at a very early stage. Although the mechanisms responsible remain to be fully elucidated, one should be aware of the potential of NSAIDs to interfere with the early phase of wound repair.

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“…64 Interestingly, in rat models, the addition of the NSAID carprofen significantly impaired the healing in ileal anastomoses (but not colocolonic) in two studies. 65,66 Of course, there have also been papers that have concluded that there is no increase in anastomotic leak with NSAID usage. 67,68 In a recent metanalysis of NSAID usage and anastomotic leaks, the authors concluded that most studies, which indicate an association of NSAIDs with anastomotic leak are flawed but, that there is still concern regarding NSAID use and leak.…”