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Evidence-based Management of Postoperative Ileus ISSUE 1 The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus Ronald S. Chamberlain, MD, MPA, FACS (Chair) Robert G. Martindale, MD Chairman of the Department of Surgery and Surgeon in Chief Saint Barnabas Medical Center Livingston, NJ Professor of Surgery Oregon Health & Science University Portland, OR OVERVIEW Postoperative ileus (POI) is defined as a transient impairment of bowel motility that may occur after major surgery. The mechanisms involved in POI are multifactorial, and include inhibitory sympathetic input; release of hormones, neurotransmitters, and inflammatory mediators; and effects of analgesics, including exogenous and endogenous opioids. A number of proactive strategies and approaches are available to help mitigate the adverse outcomes associated with POI. This is the first in a series of 3 newsletters that will examine the management of POI, and will focus on the proactive strategies that can be used by surgeons and the surgical care team to prevent or mitigate POI. LEARNING OBJECTIVES After completing this activity, readers should be able to: • Identify the underlying pathophysiological mechanisms that contribute to postoperative ileus • Compare the advantages and disadvantages of perioperative epidural and opioid analgesia in regard to postoperative ileus • Summarize the evidence that supports or opposes various postoperative treatments that are used to mitigate postoperative ileus • Explain how a multimodal approach to management of postoperative ileus can help improve outcomes and decrease time to discharge TARGET AUDIENCE This program is intended for the education of colon and rectal surgeons, general surgeons, medical/surgical nurses, and other health care providers involved in the management of postoperative ileus. ACCREDITATION AND DESIGNATION The Chatham Institute is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Chatham Institute designates this educational activity for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. The Chatham Institute LLC is an approved provider of continuing nursing education by the New Jersey State Nurses Association (NJSNA), an accredited approver by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation, provider number 175-11/2006-2009. The Chatham Institute LLC is approved by the California Board of Registered Nursing (CBRN), provider number CEP 12433. This activity is approved for 0.5 contact hours. DISCLAIMER Accreditation refers to educational content only and does not imply endorsement of products by NJSNA, ANCC, CBRN, or The Chatham Institute LLC. DISCLOSURE It is the policy of The Chatham Institute to ensure balance, independence, objectivity, and scientific rigor in all of its educational activities. All faculty, planners, and managers who affect the content of medical education activities sponsored by The Chatham Institute are required to disclose to the audience any real or apparent conflict of interest related to the activity. Faculty, planners, and managers not complying with the disclosure policy will not be permitted to participate in this activity. Ronald S. Chamberlain, MD, MPA, FACS (Chair) Speaker Bureaus: Ethicon, Inc., Pfizer Inc, sanofi-aventis U.S. LLC, Wyeth Pharmaceuticals Robert G. Martindale, MD Honoraria: Nestlé, Wyeth Pharmaceuticals SPONSORSHIP AND SUPPORT This educational activity is sponsored by The Chatham Institute and supported by an educational grant from Wyeth Pharmaceuticals, Inc. Release Date: October 31, 2007 Expiration Date: October 30, 2008 This e-newsletter is available online at: http://www.ce-university.org/surgery 1 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus Introduction mitigate POI. The second newsletter will discuss the use of opioids in the surgical setting, with a presentation of emerging agents that can help to ameliorate the adverse effect of opioids in contributing to POI. The third newsletter will discuss the management of POI, with a focus on pharmacoeconomics and cost containment. The newsletters are developed from a series of discussions between surgeons. Postoperative ileus (POI) is usually defined as a transient impairment of bowel motility that may occur after major surgery.1,2 It is considered an iatrogenic condition that is a normal consequence of abdominal or extra-abdominal surgery, including orthopedic or cardiothoracic surgery.2,3 Clinically, POI is characterized by bowel distension, lack of bowel sounds, and a lack of flatus and bowel movements.1 Symptoms include nausea, vomiting, and stomach cramps.1 Other potentially adverse effects of POI include increased postoperative pain; delay in resuming oral intake; poor wound healing; delay in postoperative mobilization; increased risk of pulmonary complications, including pneumonia, pulmonary embolism, and atelectasis; increased risk of deconditioning; prolonged hospitalization; decreased patient satisfaction; and increased health care costs.4 Postoperative Ileus: Epidurals, Inflammation, and Fluid Volume Dr. Chamberlain: Postoperative ileus is a serious problem for many patients, leading to prolonged hospital stay and delayed recovery from surgery. The question is, how do we prevent postoperative ileus, or how can we anticipate postoperative ileus and mitigate or prevent it in the perioperative period? The underlying pathology of POI is best described as a lack of coordinated bowel activity. Postoperative hypomotility can affect all segments of the gastrointestinal (GI) tract, and recovery differs by segment.4-7 Inhibited motility in the small intestine is usually transient, recovering within several hours of surgery.4 5,7 Gastric motility recovers within 24 to 48 hours after surgery,4,5 whereas the colon is usually the final portion of the GI tract to return to normal, usually within 48 to 72 hours postsurgery.4-8 Recovery of colonic motility is usually the limiting factor in resolving POI.4,9 An examination of GI recovery in patients who underwent bowel resection in 3 clinical trials found that most patients tolerated solid food and had a bowel movement by postoperative day 4, with the majority of patients discharged from the hospital by day 6.10 However, about 24% of patients required a prolonged hospital stay or readmission. The incidence of nausea was highest on the day of surgery and decreased thereafter, whereas vomiting was uncommon on the day of surgery but increased slightly on postoperative days 1 to 6.10 Dr. Martindale: There are 2 big areas that we probably need to consider. First, if possible, use an epidural for anesthesia. Second, intraoperative volume is key, though I think there is a growing amount of evidence that excess volume intraoperatively will give us more bowel edema instead of the proposed operative immobility. Inflammation of the gut as a result of surgical manipulation may also affect postoperative ileus. There are also some hints of data now coming out that the use of preoperative immune nutrition with omega-3 fatty acids may decrease postoperative ileus. After surgery, the inhibited motility of the GI tract is related to disorganized electrical activity and a lack of coordinated propulsion.4,12 In the stomach, an irregular pattern of gastric spike and slow-wave activity occurs.5 Motor activity is also disorganized in the small bowel, where the migrating motor complex (MMC), which is normally involved in propelling intraluminal contents distally during the fasting state, may be shortened and may produce retrograde contractions.4,5,13 This MMC activity is believed to be the only impetus to bowel contraction if patients are not being fed after surgery.5 Several mechanisms are believed to play a role in this altered GI motility (Table 1), contributing to a multifactorial pathophysiology.4,11 The mechanisms involved in POI are multifactorial, and include inhibitory sympathetic input; release of hormones, neurotransmitters, and inflammatory mediators; and the effects of analgesics, including exogenous and endogenous opioids.1,4,5,11 A number of proactive strategies and approaches are available to help mitigate the adverse outcomes associated with POI. This is the first in a series of 3 newsletters that will examine the management of POI, and it will focus on the proactive strategies that can be used by surgeons and the surgical care team to prevent or One of the major factors contributing to the development of POI is inhibitory reflexes.11 Inhibitory neural reflexes are activated through stimulation of somatic and visceral fibers during surgery.1,6,11 They may originate from the incision as well as from the intestines.1,6,11 Epidural local anesthetics 2 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus TABLE 1: Pathogens of postoperative ileus and treatment modalities macrophages are activated by manipulation of the intestines, such PATHOGENIC FACTOR MAY BE MODIFIED BY as occurs during abdominal surgery, Inhibitory splanchnic reflexes Epidural blockade (local anaesthetics) to secrete numerous active substances, including nitric oxide Increased efferent inhibitory sympathetic activity α- and β-antagonists Parasympathomimetics (NO) and prostaglandins.2,3,16-18 Thus, Epidural blockade (local anaesthetics) abdominal surgery triggers a chain of local inflammatory events that Local inflammation/inflammatory stress response Minimally invasive surgery Anti-inflammatory agents leads to the activation of macrophages, liberation of proinGastrointestinal peptides (VIP, substance P, CGRP) Antagonists flammatory cytokines, and upreguOpioids (exogenous) Opioid-sparing analgesic techniques lation of various adhesion moleSelective peripheral υ-opioid antagonists cules.3 This local molecular inflamOpioids (endogenous) Selective opioid receptor antagonists matory response is followed by a Starvation Early postoperative feeding cellular inflammatory phase with the Fluid excess Fluid restriction additional recruitment of circulating CGRP, calcitonin gene-related peptide; VIP, vasoactive intestinal peptide. leukocytes and a further release of cytokines, NO, oxygen free radicals, Used with permission from Holte and Kehlet, 2002. and prostaglandins into the muscu2,19 may inhibit these reflexes and help to mitigate POI.11 laris. The important role of the kinetically active Randomized, controlled studies have indicated that substances, NO and prostaglandins, in causing POI has continuous thoracic epidural blockade with local anesbeen confirmed utilizing both pharmacologic and genetic thetics for more than 24 hours decreases POI compared approaches.2,19,20 with systemic opioid administration.1,11,14,15 A meta-analysis Whereas the inflammatory cascade is well studied, the of 5 studies with 261 patients compared the effect of mechanism by which it causes a reduction in postoperative epidural local anesthetic with a combination of epidural gut motility is not completely clear.3 Manipulation of the local anesthetic and opioid on postoperative pain and small intestine not only impairs intestinal transit, but also POI.11,15 The epidural local anesthetics alone reduced POI, delays gastric emptying after surgery, indicating that other as measured by the time to the first passage of stool, by 54 mechanisms affecting motility distant from the site of hours compared with systemic opioid administration. The inflammation are probably involved in the inhibition of authors concluded that administration of epidural local motility.2,21 One possible mechanism described by Bauer and anesthetics to patients undergoing laparotomy reduces GI Boeckxstaens2 could be an interaction between the inflamparalysis compared with systemic or epidural opioids, yet matory milieu of the postoperative muscularis and the achieves comparable postoperative pain relief.15 In primary afferent neuronal activity that triggers inhibitory summary, Holte and Kehlet described the advantages of neuronal pathways. It was thus hypothesized that intestinal postoperative epidural local anesthetics to include pain inflammation in response to bowel manipulation results in relief that allows GI mobilization, the avoidance of opioidprimary afferent activation, which initiates inhibitory motor related adverse effects, and an important stress-reducing reflexes to the gut, and leads to postoperative intestinal gut effect obtained when epidural local anesthetics block dysfunction.2 afferent input from the wound.11 However, the effect of Based on the role of inflammation in POI, nonsteroidal antipostoperative epidural local anesthetics on POI compared inflammatory drugs (NSAIDs) may help to prevent the inhiwith other postoperative nonopioid analgesia is uncertain bition of bowel motility due to their anti-inflammatory propin relatively minor procedures.11 erties. In most experimental and clinical studies, giving A second major factor involved in POI is the release of NSAIDs resulted in decreased nausea and vomiting and inflammatory mediators, and inflammation has been assoimproved GI transit.5 ciated with weakened GI myoelectrical activity.3 Several Another potential contributor to POI is overhydration during animal studies have demonstrated that dormant 11 3 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus surgery. Fluid excess may potentially contribute to POI as a result of the presence of intestinal edema.22 Excessive amounts of fluid may be given in the perioperative period due to concerns about preoperative fluid deficits, attempts to support the circulation and cardiac function after general and regional anesthesia, attempts to control the circulation postoperatively, administration of crystalloid or colloid to avoid blood transfusion, and preservation of urine output.22 kg weight gain after surgery delayed the return of GI function and prolonged hospital stay in patients undergoing elective colonic resection.23 Opioids, Antagonists, and Electrolyte Balance Dr. Chamberlain: I think those are very salient features. I think pain is a big factor related to the postoperative need for opioids, and therefore opioid use is a factor in the development of ileus. So, for example, there is evidence that preemptive analgesia techniques, primarily given locally, may decrease postoperative opioid requirements. Holte and colleagues conducted a review of the data on the effects of high-volume perioperative fluid therapy and suggested that the resulting overhydration may have deleterious effects on cardiac and pulmonary function, as well as on POI, tissue oxygenation, wound healing, and coagulation.22 Fluid overload also may lead to edema of the gut, possibly contributing to enteric nutritional intolerance, prolonged ileus, and translocation of endotoxin or bacteria, with potentially serious complications such as sepsis and multiorgan failure.22 Dr. Martindale: I agree. I would maybe add that patients with any electrolyte or preoperative nutritional issues, such as hypokalemia or hypomagnesemia, are at a big risk. Even some of our outpatients come in somewhat depleted, especially if they have had a bowel prep. Opioids are of major importance in the pathogenesis of POI due to their depressive effects on GI transit.11 They are used universally as analgesics following intestinal and other surgery. However, they can complicate and prolong POI by interfering with normal GI motility (Table 2).2 The effects of postoperative intravenous fluids on recovery after colonic surgery were examined in one study that randomly assigned patients to receive postoperative intraOpioids have an inhibitory effect on gastric motility and venous fluids either according to hospital practice (≥3 L increase tone in the antrum and the first portion of the water and 154 mmol sodium per day; n=10) or on a duodenum in healthy individuals.5 Opioids have more restricted intake (≤2 L water and 77 mmol sodium per day; complicated effects on the small intestine. In vivo studies n=10).11,23 Median solid and liquid phase gastric emptying on the small intestine have demonstrated that exogenous times on the fourth postoperative day were significantly d- and l-opioid agonists abolish peristaltic activity and longer in the standard group than in the restricted group increase fasting contractile activity in humans, dogs, cats, (175 vs 72.5 min, P=0.028; and 110 vs 73.5 min, P=0.017, and monkeys.2,24,25 In humans, morphine sulfate has biphasic respectively).23 Median passage of flatus was 1 day later (4 vs 3 days, TABLE 2: Pharmacologic effects of opioids on GI function difference of 2 days [95% CI, 1-2], PHARMACOLOGIC ACTION OF OPIOIDS CLINICAL EFFECT P=0.001); median passage of stool Decreased gastric motility, emptying Increased gastroesophageal reflux was 2.5 days later (6.5 vs 4 days, difference of 3 days [95% CI, 2-4], Inhibition of small intestinal propulsion Delayed absorption of medications P=0.001); and median postoperative Inhibition of large intestinal propulsion Straining, incomplete evacuation, bloating, hospital stay was 3 days longer (9 vs abdominal distention 6 days, difference of 3 days [95% CI, Increased amplitude of nonpropulsive Spasm, abdominal cramps, and pain 1-8], P=0.001) in the standard group segmental contractions than in the restricted group, respecConstriction of sphincter of Oddi Biliary colic, epigastric discomfort tively.23 One patient in the restricted Increased anal sphincter tone, impaired reflex Impaired ability to evacuate the bowel group developed hypokalemia, relation with rectal distention whereas 7 patients in the standard Diminished gastric, biliary, pancreatic, and Hard, dry stool group had side effects or complicaintestinal secretions 23 tions (P=0.01). The authors Increased absorption of water from bowel contents concluded that positive salt and water balance sufficient to cause a 3- Used with permission from Pappagallo, 2001. 49 4 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus properties, initially stimulating motility through activation of the MMC. However, this stimulation is followed by atony, which is responsible for the slowing of GI transit.5,26 Clinical studies of the effects of methylnaltrexone are also being conducted.37,38 A controlled trial of intravenous methylnaltrexone was performed in 65 patients following open segmental colonic resection.37 Patients who had undergone segmental colectomies were randomized to either placebo or methylnaltrexone 0.3 mg/kg administered as a 20minute intravenous infusion every 6 hours. Treatments continued until 24 hours after toleration of solid foods, discharge from the hospital, or after 7 full days of treatment. Methylnaltrexone-treated patients recovered bowel function more quickly than placebo patients in all measures of upper and lower bowel recovery; the mean differences in most of the parameters of recovery were >1 day.37 No differences in opioid use or mean pain scores were observed, and the drug was well tolerated. Adverse events were similar to placebo. This study suggests that parenteral methylnaltrexone may significantly shorten the duration of postoperative bowel dysfunction following segmental colectomy.37 Opioids also have an overall inhibitory effect on the colon.4 In the colon, morphine decreases peristaltic waves and increases colonic tone, delaying stool transit and increasing water absorption from the lumen, which results in a harder, drier stool.4,5,27 The GI effects of opioids are mediated primarily by receptors within the bowel, whereas spinal or cerebral opioid receptors play a minor role.11,28,29 In addition to the effects of exogenous opioids on POI, it has been suggested that plasma concentrations of endogenous morphine are increased following surgical injury.11,30-32 The exact release mechanisms and subsequent biological effects are unknown.11,33 With repeated opioid administration for pain relief, tolerance to the analgesic effect subsequently develops; however, tolerance to the GI adverse effects does not.11,34 Therefore, limiting narcotic use in the postoperative setting has been associated with a significant decrease in the duration of POI.4,35 Electrolyte abnormalities also have been implicated in prolonged POI.4 One study found that prolonged POI associated with hypokalemia could be resolved in patients by replenishing potassium.4,40 It has also been suggested that other electrolyte abnormalities, such as hyponatremia and hypomagnesemia, play a role in POI, but this has not been confirmed.4 An alternative to limiting opioid use is to employ antagonists to counteract opioid effects on gastric motility, and several opiate antagonists have been found to have a beneficial effect.4 Two novel, peripheral opioid antagonists currently being investigated are alvimopan and methylnaltrexone. Both of these agents have a selective affinity for peripheral receptors, and do not readily cross the bloodbrain barrier. Therefore, they can reverse the negative effects of opioids on the GI tract without blocking central opioid receptors and reversing pain relief.3,4,36-38 A Multimodal Approach to Management of POI Dr. Chamberlain: What about the bariatric population? Do you think they are at a greater risk of ileus because of a decreased ability to ambulate? Dr. Martindale: No. I think we all intuitively would say that getting up and walking around will help, but the data are a bit marginal. In the postoperative bariatric population, although they do not get around much, diet is usually restricted for the first week or 2 anyway, so it is not really a big problem. A pooled retrospective subset analysis of bowel resection found that alvimopan reduced the consequences of POI after bowel resection.39 Patients had received alvimopan 6 mg (n=397), 12 mg (n=413), or placebo (n=402) at least 2 hours prior to surgery and twice daily until hospital discharge for up to 7 days. Alvimopan (6 or 12 mg) significantly accelerated GI recovery (hazard ratio=1.28 and 1.38, respectively; P≤0.001 for both).39 Alvimopan also significantly accelerated time to patient discharge by 16 hours for 6 mg and 18 hours for 12 mg (P<0.001 for both), from a mean of 147 hours for placebo. Alvimopan-treated patients had reduced postoperative morbidity compared with placebo, and incidence of prolonged hospital stay or readmission was significantly reduced (P<0.001).39 Dr. Chamberlain: Have you tried any other pharmacologic agents that might have an effect on ileus, such as metoclopramide or the erythromycins, for example? Dr. Martindale: No. Erythromycin works only in the proximal GI tract, but it does have a very rapid prophylaxis. Metoclopramide also only works in the proximal GI tract. Therefore, our prokinetic agents are more for proximal gut issues and not really for the small bowel. Dr. Chamberlain: Now, how do you think laparoscopy has 5 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus other reasons.5,42 Whereas animal studies have suggested that prokinetic agents might be effective treatments of POI, current prokinetics primarily alter upper GI motility, and generally have not been effective for treating POI.2 affected postoperative ileus? Do you think we can move patients faster by looking at laparoscopy? Dr. Martindale: I think what we learned from laparoscopy is that we found we could feed patients postoperatively more quickly. Then, we started thinking that we might be able to feed them after an open case, too. And when we started doing that, they seemed to tolerate it pretty well, too. Nasogastric tubes also do not seem to be necessary in most cases. Minimally invasive surgery leads to a decrease in the inflammatory response to surgery,43 and therefore it has been proposed to decrease POI. A review of 4 studies that examined the effects of laparoscopic surgery on POI found mixed results.11 In 2 of the studies, laparoscopic surgery reduced POI, whereas in the other 2 studies, it did not.11,44-47 A study was conducted that systematically reviewed nonrandomized comparative studies of laparoscopic resection for colorectal cancer.48 The outcomes of 6438 resections were included. The authors found that laparoscopic resection took 27.6% (41 minutes) longer to carry out than open resection. There was no significant difference between the 2 groups in early mortality rates (1.2% vs 1.1%; P=0.787) or likelihood of reoperation (2.3% vs 1.5%; P=0.319). The time until passage of first flatus, passage of a bowel movement, and tolerating oral fluids and a solid diet was 1.2 to 1.6 days (26% to 37%) shorter, measurements of pain and narcotic analgesic requirements were 16% to 35% lower, and hospital stay was 3.5 days (18.8%) shorter following laparoscopic resection compared with open resection.48 Dr. Chamberlain: So it seems that there are many variables in the care we give patients postoperatively that can be combined to improve recovery from postoperative ileus. Many individual options can improve the outcomes of postoperative ileus, and perhaps combining these options to optimize care and minimize postoperative ileus, using a multimodal approach, can provide a more comprehensive benefit to the patient. Treatment of POI has generally consisted of routine postoperative nasogastric decompression, intravenous fluids, correction of electrolyte imbalances, and expectant observation.3 Other measures that have been tried include the use of prokinetic agents, early enteral feeding, early mobilization, and the use of minimally invasive surgical techniques such as laparoscopy.3 Whereas these are standard postoperative treatments, they are not used specifically to treat POI.3 Multimodal rehabilitation programs were developed as a logical consequence of the individually positive effects on postoperative recovery and POI of these single-modality interventions.11,41 Results from multimodal rehabilitation programs suggest that an approach that includes continuous epidural analgesia, including local anesthetics, early oral feeding, and mobilization, may significantly reduce POI to a period of 1 to 2 days after colonic surgery (Table 3).11 Summary POI is a normal consequence of abdominal or extraabdominal surgery. It is characterized by bowel distension, lack of bowel sounds, and a lack of flatus and bowel movements. Adverse effects of POI include increased postoperative pain, a delay in resuming oral intake, poor wound healing, delayed postoperative mobilization, increased risk of pulmonary complications, and prolonged hospitalization. A number of interventions can help to decrease the time needed for postoperative gastric motility to return to normal function. These include epidural anesthesia with local anesthetics, laparoscopic surgical techniques, proper attention to perioperative volume control, minimal use of opioid analgesia, and ensuring proper electrolyte balance. Other treatment modalities that have not consistently been found to decrease POI include early ambulation, the use of prokinetics, and nasogastric decompression. Several opioid antagonists that are currently undergoing clinical trials may provide another pharmacologic tool for management of POI. Traditional recommendations of postoperative feeding include the use of nasogastric tubes and advancing postoperative feeding after the presence of bowel sounds. However, routine use of nasogastric tubes does not reduce POI.11 Several studies have concluded that nasogastric decompression does not shorten time to first bowel movement or decrease time to adequate oral intake.5 Furthermore, the inappropriate use of nasogastric decompression may contribute to postoperative complications such as fever, pneumonia, and atelectasis.5 In a similar way, ambulation has not been shown to improve postoperative bowel motility, although it is beneficial to patients for 6 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus TABLE 3: Treatment modalities for postoperative ileus TREATMENT MODALITY EFFECT ON POSTOPERATIVE ILUEUS COMMENTS • Nasogastric decompression None or detrimental May increase the incidence of pulmonary complications • Early ambulation None May decrease the incidence of other complications • Minimally invasive surgery Beneficial Most trials demonstrated shorter postoperative ileus • Early enteral feeding None or modestly beneficial May facilitate wound and anastomotic healing; shorter hospital stay • Epidural analgesia Beneficial Best effect is achieved when inserted at the thoracic level • Neostigmine Possibly beneficial Serious systemic side effects limit its use • Metoclopramide None Effective anti-emetic • Cisapride Beneficial Withdrawn from the US market due to serious cardiac side effects • Erythromycin None • Ceruletide Modestly beneficial Significantly increased nausea and vomiting limit its use • Somatostatin Probably none No clinical trials have been performed • Laxatives Possibly beneficial No randomized controlled trials have been performed • NSAIDs Probably beneficial Nonselective NSAIDs may increase the incidence of postoperative bleeding • Opioid antagonists Beneficial Effective only if opiates are used for pain control • Intravenous fluids restriction Probably beneficial Needs further substantiation in large clinical trials Beneficial Consists of combining the beneficial effects of several treatment modalities Nonpharmacological methods Pharmacological methods Multimodal therapy Unconventional methods • Sham feeding All need further substantiation in large randomized clinical trials Probably beneficial • Electrical stimulation Probably beneficial • Guided imagery Probably beneficial • Psychological suggestion Probably beneficial • Mechanical massage Probably beneficial • Acupuncture Probably beneficial NSAIDs, nonsteroidal anti-inflammatory drugs. Used with permission from Person and Wexner, 2006.3 7 Evidence-based Management of Postoperative Ileus The Role of the Surgeon and the Surgical Care Team: Proactive Strategies for Preventing Postoperative Ileus References 1. Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg 2000 November; 87(11):1480-93. 25. Bauer AJ, Szurszewski JH. Effect of opioid peptides on circular muscle of canine duodenum. J Physiol 1991 March;434:409-22. 2. Bauer AJ, Boeckxstaens GE. Mechanisms of postoperative ileus. Neurogastroenterol Motil 2004 October;16(Suppl 2):54-60. 26. Borody TJ, Quigley EM, Phillips SF et al. Effects of morphine and atropine on motility and transit in the human ileum. Gastroenterology 1985 September;89(3):562-70. 3. Person B, Wexner SD. The management of postoperative ileus. Curr Probl Surg 2006 January;43(1):6-65. 27. Kaufman PN, Krevsky B, Malmud LS et al. Role of opiate receptors in the regulation of colonic transit. 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