|Year : 2017 | Volume
| Issue : 2 | Page : 50-53
Therapeutic management of postoperative ileus
Lei Zhang1, Xiaohui Xu2
1 Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
2 Department of Chemical Drug, Lanzhou Institutes for Food and Drug Control, Lanzhou, Gangsu, China
|Date of Submission||22-Dec-2016|
|Date of Acceptance||12-Mar-2017|
|Date of Web Publication||22-Jun-2017|
Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong
Source of Support: None, Conflict of Interest: None
Postoperative ileus is one of the most common complications in patients after abdominal surgery and is a major determinant of recovery after surgery. It leads to increased postoperative morbidity, prolonged hospital stay, and increased costs. The pathogenesis of postoperative ileus is multifactorial, including pharmacological, neurogenic, and inflammatory mechanisms. In this review, we discuss the current therapeutic strategies for postoperative ileus.
Keywords: Postoperative ileus, pathogenesis, therapeutic strategies
|How to cite this article:|
Zhang L, Xu X. Therapeutic management of postoperative ileus. Transl Surg 2017;2:50-3
| Introduction|| |
Postoperative ileus is characterized by inhibition of intestinal motility in the postoperative setting , and is one of the most common types of postoperative complication after major noncardiac surgery. The incidence of postoperative ileus is generally between 10% and 30% for abdominal surgery.,,, The clinical manifestations include abdominal distension, nausea, vomiting, and the inability to pass stools or tolerate a solid diet. Importantly, postoperative ileus is a major determinant of postoperative recovery. It often causes other potential complications and leads to increased postoperative morbidity due to infectious, pain-related, pulmonary, and renal problems, as well as prolonged hospitalization, which is a great economic burden to health-care systems. The pathogenesis of postoperative ileus is multifactorial and involves neurogenic, inflammatory, and pharmacological mechanisms. Although a variety of strategies have been proposed to reduce postoperative ileus, such as early ambulation, fluid restriction, minimally invasive surgery, and enhanced recovery after surgery protocols, none of these has been completely successful in preventing postoperative ileus. In this review, we focus on the latest insights into the therapeutic approaches to patients with postoperative ileus.
| Mechanisms of Postoperative Ileus|| |
Postoperative ileus is one of the most common clinical complications after abdominal surgery. Postoperative ileus may be generally defined as a postoperative transient impairment in gastrointestinal motility. Various factors have been shown to contribute to the pathogenesis of postoperative ileus, such as the use of opioids, activation of inhibitory reflexes, and inflammatory mediators. Postoperative ileus is not only restricted to the small intestine but also involves the entire gastrointestinal tract. The mechanisms underlying the generalized inhibition of gastrointestinal motility in response to this local inflammation comprise a complex neuronal and immunological response.
The initial trigger of the inflammatory cascade is unclear and could involve dendritic cells, mast cells, and/or macrophages. In mouse studies, peritoneal mast cells were activated, which caused a subsequent release of mast cell mediators and an inflammatory response in the intestine. Intestinal surgery during hysterectomy causes a release of tryptase (a mast cell activation marker) in the peritoneal fluid followed by an increase in levels of interleukin-6 (IL-6) and IL-8. During the past decades, the importance of the vagus nerve in intestinal immunity has been established. In a mouse model, electrical stimulation of the vagus nerve reduces macrophage activation and intestinal muscular inflammation and improves postoperative ileus. It demonstrates that interaction between the nervous and immune system modulates intestinal inflammation.
Several other mechanisms have been shown to play an important role in postoperative ileus. In the gastrointestinal tract, opioids mainly exert their action on the enteric nervous system, where they bind to opioid receptors in the submucosal plexuses and myenteron and cause bowel dysfunction. It is acknowledged that abdominal surgery triggers a short-lasting neurogenic phase and a clinically more relevant longer lasting inflammatory phase. The neurogenic phase is triggered during surgery through activation of adrenergic and nitrergic inhibitory reflex pathways. Release of inflammatory mediators as well as the migration of leukocytes into the intestinal wall has been shown to correlate with the paralysis of gastrointestinal tract.
Sympathetic hyperactivity generates high levels of catecholamines in the postoperative period leading to postoperative ileus. Plasma catecholamines have been demonstrated to be elevated in the postoperative period, and high levels of catecholamines have been associated with inhibited gastrointestinal motility. Adrenergic blocking agents have been found to improve gastrointestinal motility in animal studies.
| Current Therapies for Postoperative Ileus|| |
Fast-track recovery surgery
Fast-track recovery surgery combines various techniques used in the care of patients undergoing elective operations and includes epidural or regional anesthesia, the use of minimally invasive techniques, optimal pain control, early enteral nutrition, and ambulation. The combination of these approaches reduces the stress response and organ dysfunction and therefore greatly shortens the time required for full recovery of the gastrointestinal tract.
Local anesthetics such as lidocaine reduce pain perception and also decrease inflammation. Lidocaine decreases sympathetic nervous system activity and has a direct excitatory effect on intestinal smooth muscle. Most trials demonstrated a statistically significant benefit of lidocaine on postoperative ileus and length of hospital stay, but a small number of trials and the exact mechanism of action remain unclear.,
Minimally invasive surgery using laparoscopy has many potential advantages over open surgery, including smaller incisions, reduced pain and inflammation, earlier gastrointestinal recovery, and shorter hospital stays. A 2012 meta-analysis that included 4,614 patients with colon cancer demonstrated that laparoscopic surgery considerably reduced the time until recovery of bowel function and the duration of hospital stay compared with open surgery. Moreover, among patients receiving fast-track care, those who underwent laparoscopy had shorter hospital stays than patients who underwent open colectomy. Despite the apparent effectiveness of the fast-track recovery surgery, this has not been fully implemented in the majority of surgical wards. Strategies to increase the implementation of this fast-track recovery surgery should be encouraged.
Sham feeding has been reported to stimulate bowel motility in humans. There has been recent interest in using chewing gum as a form of sham feeding to reduce rates of postoperative ileus. A meta-analysis of 26 randomized controlled trials (RCTs) enrolling 2,214 patients investigated gum chewing as a treatment for postoperative ileus after colorectal surgery. Daily gum chewing was started after colorectal surgery and led to a decrease in the duration of postoperative ileus. The exact mechanism of action remains unclear, but it is possible that sham stimulation of the vagus nerve could trigger the cholinergic anti-inflammatory pathway.
Opioid agonists are often used for postoperative analgesia and contribute to postoperative ileus by decreasing intestinal motility through stimulation of μ-type opioid receptors in the gut. Alvimopan is a peripherally acting opioid agonists and belongs to a new class of drugs designed to reverse opioid-induced gastrointestinal effects. A review of four RCTs that studied the role of alvimopan after open bowel resection showed that the use of the drug led to a reduction in the time until tolerance of solid food and bowel movement and a statistically significant reduction in the duration of hospital stay. However, the use of alvimopan has since been associated with an increased rate of myocardial infarction, limiting its clinical application.,, Methylnaltrexone, similar to alvimopan, is a peripherally acting opioid receptor antagonist, but it does not readily cross the blood-brain barrier. Methylnaltrexone has been evaluated as a potential treatment for postoperative ileus.
Gastroprokinetic agents enhance gastrointestinal motility by increasing the frequency of contractions in the small intestine. They are used to relieve gastrointestinal symptoms such as abdominal discomfort, bloating, constipation, heartburn, nausea, and vomiting. Gastroprokinetic agents may increase acetylcholine concentrations by stimulating the M1 receptor which causes acetylcholine release. Higher acetylcholine levels increase gastrointestinal peristalsis, thereby stimulating gastrointestinal motility and accelerating gastric emptying. A 2008 Cochrane review that evaluated the benefits of prokinetic agents, including 15 systemic acting prokinetic drugs such as cisapride, erythromycin, lidocaine, cholecystokinin, and dopamine antagonists, indicated that administration of gastroprokinetic agents for prevention of postoperative ileus is not recommended due to lack of evidence or absence of effect. However, most trials enrolled a small number of patients and showed moderate to poor methodological quality, which makes it difficult to draw any solid conclusion. Clinical studies have reported conflicting results. Therefore, further studies are required.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase-2 (COX-2) and prevent arachidonic acid conversion to prostaglandin H2. Interestingly, the use of NSAIDs after surgery was associated with a decreased risk of postoperative ileus in women undergoing debulking surgery for ovarian carcinoma. Novel COX-2 inhibitors have been developed to achieve analgesic, antipyretic, and anti-inflammatory activity. These COX-2 inhibitors are commonly used in the postoperative care and as a part of multimodal early recovery management. As prostaglandins have been proposed to have a crucial role in reducing gastrointestinal motility following surgery, selective COX-2 inhibitors administered before surgery should improve postoperative ileus. A clinical trial in which patients were given 40 mg oral valdecoxib resulted in a reduction of the time to first bowel sound and movement, first passage of flatus, and tolerance of solid diet together with a reduction in the duration of hospital stay.
| Other Potential Strategies|| |
The mast cell stabilizer ketotifen reduced muscular inflammation and shortened disease duration in a mouse model of postoperative ileus, leading to a pilot study, in which sixty patients undergoing abdominal surgery were treated with ketotifen for 6 days. Although gastric emptying was markedly improved by ketotifen, no improvement of colonic transit was observed. More potent mast cell stabilizers might be more effective.
In addition, adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), which can be induced by inflammatory cytokines, are expressed by vascular endothelial cells and subsets of leukocytes. Treatment with monoclonal antibodies against ICAM-1 prevents immune cell infiltration and improved gastroplegia. These suggest that targeting adhesion molecules could be a useful approach to prevent postoperative ileus.
Propranolol, a nonspecific β-receptor antagonist, has been investigated for the treatment of postoperative ileus; however, it demonstrated variable results. The effects of these agents have not been adequately studied. Therefore, they are not used in the treatment of improving postoperative ileus. Neostigmine is an acetylcholinesterase inhibitor that causes an increase in parasympathetic activity in the gastrointestinal tract, which is believed to stimulate colonic motility. The clinical usefulness of neostigmine may be limited by adverse effects including abdominal cramps and vomiting.
| Conclusion|| |
Postoperative ileus is a major clinical complication and there is currently no universally recognized treatment. Its pathogenesis is multifactorial. Intervening in the adaptive immune response might reduce the duration of postoperative ileus. In addition, improvements in recovery time such as fast-track care have been obtained since the introduction of perioperative strategies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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