Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase (COX) 2 inhibitors
As described above, the secretion of prostaglandins via COX 2 is a key element in the inflammatory phase. COX or prostaglandin G/H2 synthase allows the conversion of arachidonic acid into prostaglandin H2 and is the target of NSAIDs (Wallace, 2007). NSAIDs therefore appear to be attractive molecules for the prevention of ileus, particularly in its inflammatory phase. However, COX inhibitors, including selective COX 2 inhibitors, are responsible for adverse effects in the digestive tract (Wallace et al., 2000). These adverse effects include peptic ulceration or, in the case of gastrointestinal surgery, an increase in the rate of anastomotic fistula (Elia et al., 2005). They can be explained by the role of prostaglandin in the digestive tract. Indeed, they are notably secreted in the gastric mucosa and are one of the mediators for maintaining the integrity of the gastric mucosa. When the gastric mucosa is exposed to a toxic substance, prostaglandins help maintain gastric blood flow, the secretion of bicarbonates and mucus on the surface of the epithelial cells, thus preserving epithelial homeostasis (Wallace et al., 2004). Studies conducted in the 1980s have further defined the mechanism by which prostaglandins contribute to mucosal defence and the mechanisms by which NSAIDs impair the ability of the gastrointestinal mucosa to resist and respond to damage (Wallace, 2007). The studies have identified two COX isoforms, COX1, which allows the synthesis of protective prostaglandins in the gastrointestinal tract, and COX2, which is involved in inflammation (Xie et al., 1991). However, it appears that both isoforms are involved in the defence mechanisms of the gastrointestinal mucosa, although COX2 selective inhibitors generate fewer serious adverse effects than non-selective NSAIDs(Tanaka et al., 2001). A phase II multicentre randomised controlled clinical trial of 210 patients undergoing major abdominal surgery was conducted by Wattchow et al. in Australia. Patients were randomised to three groups and treated twice daily with celecoxib 100 mg, diclofenac 50 mg and placebo (Wattchow et al., 2009). The celecoxib group had significantly fewer patients with postoperative ileus (n=1) than the diclofenac (n=7) and placebo (n=9) groups (Wattchow et al., 2009). However, given the protective functions of COX and prostaglandins on mucosal healing, there are obstacles to the routine use of NSAIDs. Indeed, the literature reports inconsistent results, particularly on the rate of postoperative fistulae and the use of NSAIDs, leading to reluctance on the part of the surgical and anaesthetic teams (Gorissen et al., 2012; Saleh et al., 2014; Subendran et al., 2014). Nevertheless, in certain categories of patients with less risk of developing anastomotic fistula or septic complications, the results on transit time and pain control merit consideration of the administration of a selective COX2 inhibitor.