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.