Pharmacologic Options to Prevent Postoperative Ileus

Center for Drug Policy, Partner's Healthcare, Needham, MA 02494, USA.
Annals of Pharmacotherapy (Impact Factor: 2.06). 07/2009; 43(9):1474-85. DOI: 10.1345/aph.1M121
Source: PubMed


To summarize the evidence on pharmacologic options in preventing postoperative ileus (POI).
The Cochrane Database of Reviews and OVID databases and Food and Drug Administration (FDA) Web site were searched (1950-April 2009) using the term postoperative ileus.
Meta-analyses and randomized controlled trials were included for review. The FDA Web site was searched for clinical reviews and label information for drugs indicated for the prevention of POI.
Three meta-analyses, 2 on gum-chewing and 1 on alvimopan, and 18 clinical trials were identified. Only gum chewing and alvimopan were effective in preventing POI. Gum chewing reduced the time to first flatus and bowel movement (weighted mean difference 21h; p = 0.0006 and 33h; p = 0.0002, respectively). In one meta-analysis, gum chewing significantly reduced length of stay (LOS) by 2.4 days (p < 0.00001) but this was not replicated in the second meta-analysis. Alvimopan shortened the time to reach a composite endpoint of solid food intake, plus/minus flatus, and bowel movement (93 vs 105 h; p < 0.001). A higher incidence of myocardial infarction was observed in a 12-month study of alvimopan for the treatment of opioid-induced bowel dysfunction, but not in studies in patients undergoing bowel resection. Alvimopan decreased the time to written hospital discharge order (hazard ratio 1.35; p < 0.01), while the significance of a reduction in LOS (0.2-1.3 days) was not reported.
Gum chewing and alvimopan are effective in preventing POI, but given safety concerns and higher cost with alvimopan, gum chewing may be preferred.

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Available from: Elissa V Klinger, Jan 05, 2015
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    • "Department of Physiology and Pharmacology, Faculty of Medicine, INCT–IBISAB–Brazilian Semi-Arid Institute of Biomedicine, 60430-270 Fortaleza, Ceará, Brazil e-mail: H. de Sousa Magalhães : M. T. S. Trevisan Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60451-970 Fortaleza, Ceará, Brazil D. de Araújo Viana Laboratory of Pathology and Legal Medicine, Faculty of Veterinary, State University of Ceará, 60740-000 Fortaleza, Ceará, Brazil and Blum 2009; Johnson and Walsh 2009; Yeh et al. 2009 "
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    ABSTRACT: Our previous study has shown that mangiferin (MGF), a glucosylxanthone from Mangifera indica, exerts gastrointestinal prokinetic action involving a cholinergic mechanism. Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. The present study investigated to know whether MGF having anti-inflammatory and prokinetic actions can ameliorate the intestinal inflammation and impaired gastrointestinal transit seen in the mouse model of POI. Experimental POI was induced in adult male Swiss mice by standardized small intestinal manipulation (IM). Twenty-four hours later, gastrointestinal transit was assessed by charcoal transport. MGF was administered orally 1 h before the measurement of GIT. To evaluate the inflammatory response, plasma levels of proinflammatory cytokines TNF-α, IL-1β, IL-6, and chemokine MCP-1, and the myeloperoxidase activity, nitrate/nitrite level, and histological changes of ileum were determined in mice treated or not with MGF. Experimental POI in mice was characterized by decreased gastrointestinal transit and marked intestinal and systemic inflammatory response. MGF treatment led to recovery of the delayed intestinal transit induced by IM. MGF in ileum significantly inhibited the myeloperoxidase activity, a marker of neutrophil infiltration, and nitrate/nitrite level and reduced the plasma levels of TNF-α, IL-1β, IL-6, and MCP-1 as well. MGF treatment ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in the mouse model of POI.
    Full-text · Article · Feb 2015 · Archiv für Experimentelle Pathologie und Pharmakologie
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    • "Similarly, mosapride also antagonizes the 5-HT3 receptor that reduces intestinal contractility, slows colonic transit, and increases fluid absorption. These properties may explain why mosapride exerts potent prokinetic effects in the upper GI tract but has less clear effects on colonic motility both in vitro and in vivo.8,19-21 "
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    ABSTRACT: Purpose Postoperative ileus (POI) is an impairment of coordinated gastrointestinal (GI) motility that develops as a consequence of abdominal surgery and is a major factor contributing to patient morbidity and prolonged hospitalization. The aim of this study was to investigate the effects of different 5-hydroxytryptamine 4 (5-HT4) receptor agonists, which stimulate excitatory pathways, on a POI model. Materials and Methods The experimental model of POI in guinea pigs was created by laparotomy, gentle manipulation of the cecum for 60 seconds, and closure by suture, all under anesthesia. Different degrees of restoration of GI transit were measured by the migration of charcoal. Colonic transit was indirectly assessed via measurement of fecal pellet output every hour for 5 hours after administration of various doses of mosapride, tegaserod, prucalopride, and 5-HT. Results Charcoal transit assay showed that various 5-HT4 receptor agonists can accelerate delayed upper GI transit in a dose-dependent manner. However, fecal pellet output assay suggested that only prucalopride had a significant effect in accelerating colonic motility in POI. Conclusion Although mosapride, tegaserod, and prucalopride produce beneficial effects to hasten upper GI transit in the POI model, prucalopride administered orally restores lower GI transit as well as upper GI transit after operation in a conscious guinea pig. This drug may serve as a useful candidate for examination in a clinical trial for POI.
    Full-text · Article · Jul 2013 · Yonsei medical journal
    • "Various systematic reviews and meta-analyses have also found a significant reduction in time to first flatus as well as bowel movement in the gum chewing group [Table 5].[5–81418] "
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    ABSTRACT: There is ample evidence in the recent literature that gum chewing after elective colonic anastomosis decreases postoperative ileus (POI). But there are very few studies on small bowel anastomosis done in relaparotomy cases. This study aimed to evaluate the effect of gum chewing on the duration of POI following small bowel anastomosis performed for the closure of intestinal stoma, made as temporary diversion in the selected cases of typhoid perforation peritonitis. Hundred patients undergoing elective small bowel anastomosis for the closure of stoma were randomly assigned to the study group (n=50) and the control group (n=50). The study group patients chewed gum thrice a day for 1 h each time starting 6 h after the surgery until the passage of first flatus. The control group patients had standard postoperative treatment. Study and control group patients were comparable at inclusion. The mean time for the appearance of bowel sounds as well as the passage of first flatus was significantly shorter in the study group (P=0.040, P=0.006). The feeling of hunger was also experienced earlier in study group cases (P=0.004). The postoperative hospital stay was shorter in the study group, but the difference was not significant (P=0.059). The cases of relaparotomy requiring additional adhesiolysis and small bowel anastomosis for stoma closure are benefited by postoperative gum chewing.
    No preview · Article · Mar 2012 · Saudi Journal of Gastroenterology
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