Diclofenac causes more leakage than naproxen in anastomoses in the small intestine of the rat

Abstract

Non-steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated. In 104 male Wistar rats, an anastomosis was constructed in both colon and ileum. The rats were divided into groups who received diclofenac (4mg kg(-1) day(-1)) or naproxen (10mg kg(-1) day(-1)) daily from the day of surgery or from day 3 after surgery. Animals were killed on day 3 or 7 and analysed for signs of anastomotic dehiscence and wound strength of anastomoses and abdominal fascia. Anastomotic leakage in the ileum (p < 0.0001) and mortality rates (p = 0.001) were significantly increased in the diclofenac group. On day 7, the anastomotic bursting pressure in the ileum remained below that of the controls in the diclofenac- and naproxen-treated rats. When administration of diclofenac was postponed to day 3 after surgery, anastomotic dehiscence was almost absent. The colonic anastomosis and abdominal wall always remained unaffected. This study implies that immediate postoperative administration of diclofenac and, to a far lesser extent, naproxen can affect healing in the ileal anastomosis in the rat. This negative effect can be prevented by a short postoperative delay in administration. On steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated.