Despite no consensus on the definition of POI, transient impairment of bowel motility is widely accepted [8]. Postoperative ileus is defined as transient and functional bowel movement defect following surgery [8]. Ileus commonly occurs after colorectal surgery and may cause serious complications and prolonged hospital stay. According to the United States data, POI leads to an increase in the length of the hospital stay and readmissions which result in an increase of US $ 1.5 billion per year in cost [9]. POI is considered to be multifactorial as many factors influence postoperative surgical stress response that yields to prolongation of bowel movement and development [10]. Several risk factors were defined including age, BMI, operation time, degree of bowel manipulation, surgical trauma level, postoperative opiate utility in pain management, prolonged anesthesia, intraoperative bleeding, limited iv fluid administration, and early postoperative feeding. Similarly, several preventive methods have been investigated like gum chewing [11–13], acupuncture [14], early feeding [15] early mobilization [16]. Some of these were argued to be included in ERAS protocols [17]. According to our knowledge, this study is the first one to compare only iv fluid administered control group to gum, nicotine gum, and sham feeding (ice-cream) groups for the treatment of POI in colorectal surgery. The para-sympathomimetic nicotine-containing gum chewing was found to be effective in the treatment of POI after rectum resection. This result is encouraging to plan further trials including more patients and different doses of nicotine.
In the pathophysiology of postoperative ileus, early neurogenic pathway and late inflammation in the intestinal wall are accused [18]. The mechanism of sham nutrition is the induction of complex cephalic vagal response by chewing. The response leads to both humoral and nervous stimulation of bowel motility. Sham nutrition is widely used in the treatment of postoperative ileus, but its effect is still controversial. The most commonly used agent in this regard is gum chewing. Studies on gum chewing after abdominal surgery reported good results, but there are clinical studies that do not support these findings. Vasquez et al. reported in their meta-analyses involving 6 studies chewing gum after colorectal surgery was effective in the treatment of postoperative ileus [3]. Ho et al. evaluated 10 studies on gum chewing after colorectal surgery and found that the method was safe and shortened the length of hospitalization, but they also mentioned the data they used were heterogeneous [16]. In another study, when compared with the control group, the positive effects of gum chewing on paralytic ileus were not shown in left colon resections [19]. Cochrane analysis indicated that gum chewing may have positive effects on the recovery of the gastrointestinal system postoperatively, but further studies are needed due to the poor quality of the studies [20].
The amount of intravenous fluid given during abdominal surgery may have effects on the paralytic ileus. Studies have shown that restricted fluid infusion may reduce the frequency of the impaired bowel movement [21, 22]. Lee et al. compared the characteristics of patients who developed and did not develop postoperative ileus and found a history of severe constipation and higher amounts of operative bleeding which were related to POI development [23]. Amount of operative intravenous fluid infusion, amount of perioperative bleeding, and preoperative constipation scores were examined in our study, and no difference was found between the groups. We also evaluated patients in terms of demographic specifications, previous abdominal surgery, type of surgery (open or laparoscopic), duration of the procedure, drain usage, etiology, and neoadjuvant treatment to eliminate other factors that might compromise the results.
Early postoperative feeding is recommended after colorectal surgery, and many have demonstrated efficacy in the Enhanced Recovery After Surgery (ERAS) protocols. Ice cream is used in many protocols and is recommended for early feeding after colorectal surgery [24]. In our study, we could not detect a positive effect of early enteral feeding with ice cream on POI.
Nicotine, a strong para-sympathomimetic included gum chewing may shorten the postoperative ileus by acting on early neurogenic pathway and late inflammation in the intestinal wall [18]. The study demonstrated positive effect of nicotine gum in postoperative ileus management when compared to the control and sham feeding groups. The main goal of nicotine gum utility in the study was the strong para-sympathomimetic effect of nicotine. Leuzinger et al. [25] reported using a nicotine patch as an alternative treatment for a patient with Ogilvie syndrome in 1996. Several years later, Wu and colleagues hypothesize that chewing gum containing nicotine may be an effective method of postoperative ileus treatment. In this study, it was emphasized that the cholinergic anti-inflammatory effect of both the cephalic vagal route and nicotine could be used with this method [6]. Lambrichts et al reported that nicotine gum was safe but ineffective in the treatment of prolonged postoperative ileus in a multicenter randomized study [26].
In the pathophysiology of postoperative ileus, the neurogenic pathway is responsible early in the event, while the inflammatory pathway is active in the late period [18]. The cause of impaired bowel activity is the inflammatory cells that infiltrate the gut muscular layer during the late period. Nicotine may suppress this second mechanism by the cholinergic anti-inflammatory effect [27].
Nicotine also has some potential positive effects. It reduces the need for opioids, which are one of the causes of prolonged paralytic ileus in the postoperative period [28]. In experimental studies, nicotine stimulated angiogenesis by stimulating endothelial nicotinic acetylcholine receptors, thereby increasing wound healing [29, 30]. Side effects of nicotine chewing gum have been well studied since they are used for smoking cessation for a very long time. In Cochrane analysis conducted in 2012, the most significant side effect of nicotine chewing gum was found to be irritation in the mouth and throat, and no evidence was found that nicotine replacement treatments increased the risk of heart attack [31].
This study has restrictions due to the low number of patients. Obtained favorable results in the management of POI may encourage further studies including a larger number of patients and comparing different doses of nicotine.