Postoperative Ileus reduction by NicOtine gum CHewing after Operation

Postoperative ileus (POI) is a common complication after abdominal surgery. It
is a transit cessation of bowel mobility after surgery and presents as an
inability to tolerate enteral nutrition, associated with nausea, abdominal
distension, and lack of flatus and defecation. Although bowel function
literally recovers within 3 to 5 days after operation, in more than 50% cases
however, it is not fully recovered 4 days post operation.
Delayed recovery of bowel function leads to other serious morbidity such as
pulmonary complications, hospital-acquired infections, longer hospitalization,
and of course this results in a large increase of medical cost as well.

Surgical procedures trigger two different phases of POI: an early neurogenic
phase and a late inflammatory response. The latter one is considered to be a
more clinically relevant cause of gastrointestinal dismotility [6]. Multimodal
fast-track perioperative care programs, including adequate pain relief, minimal
invasive surgery, early enteral nutrition, are now being clinically used on
patients in order to shorten the duration of POI, but limited effects
restricted its further implementation. At the same time, with regard to the
second phase of POI pathophysiology, the inhibition of the inflammatory (2nd)
phase, remains unsolved.

Recently, stimulation of vagus nerve has been targeted for the prevention of
POI. A number of studies concentrate on the physical, pharmacological,
electrical stimulations of the vagus nerve in order to prevent or attenuate
POI. In experimental models, cholinergic anti-Inflammatory pathway mediated by
the vagus nerve could significantly increases bowel motility as well as
controls inflammatory cell recruitment and thus prevent the pathological
changes of POI .

Sham feeding, which mimics the cephalic phase of digestion, stimulates the
electrical, motor, and secretory activities of the gastrointestinal tract
through neurohormonal and vagal pathways. Since Asao et al. first demonstrated
that gum chewing, as a form of sham feeding, stimulated bowel motility and
aided the early recovery from POI in the clinic, several randomized clinical
trials have reported similar results on patients who underwent various types of
surgery.

Nicotine, a selective cholinergic agonist, is considered as an essential
regulator of the *cholinergic anti-inflammatory pathway*. In animal models,
nicotine has been shown to improve survival rates of sepsis by stimulating
alpha7 nicotinic acetylcholine receptor (nAchR)]. Experimental studies have
also shown the effect of specific alpha7 receptor agonist (AR-R17779)
ameliorating POI in rats [7], while other nAchR also play important roles
mediating the cholinergic anti-inflammatory pathway. In addition, clinical
evidence showed pre-operative nicotine administration significantly reduced
postoperative opioid consumption, while reducing opioids was also an important
strategy of shortening POI. Interestingly, the alpha7 nicotinic receptor also
plays a role in nicotine-caused analgesia, so its activation induced by
nicotine may benefit the control of postoperative pain as well as shortening
POI.

Based on the above reasons, and because nicotine gum chewing combines the
cephalic vagal reflex induced by gum chewing, its cholinergic anti-inflammatory
effect and analgesic modulation induced by nicotine administration, it might be
beneficial for the prevention of POI. Nicotine gum (2 mg) chewing may reduce
POI and result in better patient outcomes such as reducing postoperative opioid
consumption, accelerating the recovery of bowel motility, shortening the length
of hospitalization and thus improving the postoperative recovery and quality of
life as well as saving medical costs.

The aim of this project is to study the effect of nicotine gum chewing in the
prevention or reduction of POI and reduction of opioid use on patients who
underwent elective colorectal surgery, and evaluate its safety and possible
adverse effects.

randomized controlled trial (pilot)

In total the patient will chew 1 piece of gum before operation and 3 times per
day after surgery until the first passage of defecation.

There is no serious extra risk for a patient that is participating is this
trial. The possible side effects of nicorette are mostly seen in higher dosage.
Vena punction risks are minimal.
Possible benifit: earlier recovery of bowel motility after surgery.