PRACTICAL GASTROENTEROLOGY • DECEMBER 2002 13

INTRODUCTION

Postoperative ileus (POI) is a very common prob-lem after many surgical procedures, may lead tosignificant patient morbidity, and is a common

reason for gastroenterological consultation. POI maybe generally defined as transient inhibition of normalGI motility in the postoperative setting, typically last-ing 3-5 days after surgery. Clinical consequences ofPOI include worsened postoperative pain, nausea andvomiting, delay in resuming enteral nutrition, and pro-longed hospitalization. Other postoperative complica-tions, including deconditioning, malnutrition, andincreased risk of nosocomial infections and pulmonarycomplications, may also be increased. (Table 1) Theeconomic impact of POI is significant, estimated to be$750 million in the US in 1986 and approaching $1billion in 2000 (1).

Despite its pervasiveness, the pathophysiology ofPOI remains poorly understood, and treatment optionsare currently limited. Several mechanisms are thoughtto play a role in POI, including sympathetic neural

reflexes, local and systemic inflammatory mediators,and changes in various neural and hormonal transmit-ters. Treatment is generally supportive in nature, andclinical trials evaluating different therapies are oftenlimited by small size, retrospective design, and/or end-points that make comparisons to other trials difficult.This article focuses on our current understanding ofthe pathophysiology of POI, and will review the clini-cal presentation, evaluation, and current treatmentoptions in patients with POI.

PATHOPHYSIOLOGYSeveral different mechanisms have been proposed inthe pathogenesis of POI. Neural reflexes involving thesympathetic nervous system are thought to inhibitpostoperative intestinal motility. Early studies foundthat intestinal motility could be improved in animalspostoperatively by transecting the spinal cord orsplanchnic nerves. Subsequent work evaluating theutility of epidural anesthetic agents consistently founddecreased duration of postoperative ileus, presumablydue to the blockade of neural reflexes at the cord level(2). Local and systemic inflammatory mediators arealso thought to play a role in POI (3). Surgical manip-

Postoperative Ileus

A SPECIAL ARTICLE

Brian Behm M.D. and Neil Stollman M.D., F.A.C.P.,F.A.C.G., Division of Gastroenterology, University ofCalifornia at San Francisco, San Francisco, CA.

by Brian Behmand Neil Stollman

PRACTICAL GASTROENTEROLOGY • DECEMBER 200214

A SPECIAL ARTICLE

Postoperative Ileus

ulation of the bowel produces a local inflammatoryresponse that is associated with smooth muscle dys-function in small bowel and colonic tissue in animalstudies. Nonsteroidal antiinflammatory (NSAID) med-ications have been found to decrease the duration ofPOI, thought to be due to their antiinflammatory prop-erties. Various cytokines, including IL-1 and IL-6, areelevated in the postoperative setting and may also playa role in POI. Neural and hormonal factors, includingvasoactive intestinal peptide (VIP), substance P, andnitric oxide (NO), also appear to be involved in thepathogenesis POI, but the relative roles of these vari-ous mediators remains to be defined.

External factors also influence the duration of POI.The type of surgical procedure can have significanteffects on postoperative bowel function. Skin incisionhas minimal effect on bowel motility, whereas openingthe peritoneal cavity completely abolishes coordinatedgut motility. Major surgical procedures not involvingthe abdominal cavity frequently have minimal ileuspostoperatively. In addition, intestinal manipulationappears to increase the duration of POI, with thedegree of bowel manipulation during surgery beingdirectly proportional to the duration of ileus. Abdomi-nal surgery done laparoscopically may reduce theduration of POI compared to open surgical proceduresdespite often longer procedure times, presumably dueto decreased bowel manipulation with laparoscopy.

Opiates, while frequently necessary for analgesia inthe postoperative setting, also delay the return of nor-mal bowel function by binding to peripheral opiatereceptors located in the GI tract. Postoperativehypokalemia and infections have also been found toprolong POI (Table 2).

CLINICAL PRESENTATIONDespite its prevalence, there is no standard nomencla-ture or grading system for POI. POI may be generallycharacterized by abdominal distension, lack of bowelsounds, and lack of passage of flatus or stool. Symp-toms may include abdominal pain and bloating, nau-sea, vomiting, and anorexia (Table 3). The pain of POIis typically mild and constant, in contrast to the parox-ysmal severe pain associated with mechanical bowelobstruction. POI affects all parts of the gastrointestinaltract to varying degrees. Small intestinal motor func-tion typically returns first, often within several hoursof surgery. Gastric motility may return 24–48 hoursafter surgery. Colonic function is last to return, gener-ally occurring 48–72 hours after surgery. The return ofcolonic motility is thought to be the frequent rate-lim-iting step in the resolution of POI.

No single variable has been found to accuratelypredict the resolution of ileus. Return of bowel soundsmay only indicate the return of small bowel motility,and does not appear to be a good marker for resolutionof ileus. Passage of flatus also may be an unreliablemarker as it may be overlooked or underreported bysome patients. The passage of stool is another way to

(continued on page 17)

Table 1 Postoperative ileus: potential complications

• increased postoperative pain•increased nausea and vomiting•delay in resuming oral intake•poor wound healing•delay in postoperative mobilization•increased risk of other postoperative complications

– deconditioning– pulmonary complications (pneumonia, pulmonary

embolism, atelectasis)– other nosocomial infections

•prolonged hospitalization•decreased patient satisfaction•increased health care costs

Table 2Pathophysiology of postoperative ileus: proposed mechanisms

• Spinal and local sympathetic neural reflexes• Local and systemic inflammatory mediators• Exacerbating factors:

– opioid analgesics– intraperitoneal surgery– degree of bowel manipulation– open (vs. laparoscopic) surgical procedures– hypokalemia

PRACTICAL GASTROENTEROLOGY • DECEMBER 2002 17

A SPECIAL ARTICLE

Postoperative Ileus

assess the return of bowel function, but does notalways correlate well with patients’ ability to tolerate anormal diet.

Physical exam should focus on the abdomen. Aus-culation of the abdomen will frequently reveal a lackof bowel sounds. There may also be increased abdom-inal girth, lack of visible peristalsis, and a tympanicabdomen. Abdominal roentgenographs may revealscattered air-fluid levels or nonspecific patterns ofsmall and large bowel gas. Laboratory tests shouldinclude the evaluation of serum electrolytes and eval-uation for infection.

TREATMENT(Table 4)

NonpharmacologicNasogastric (NG) intubation has been used for over 50years as a supportive measure after abdominal surgery.However, recent studies have suggested NG tubesshould not be routinely placed after abdominal surgery.In a meta-analysis that evaluated selective versus rou-tine NG intubation, there was no significant differencein the duration of ileus between the two groups, butpatients having routine NG tube placement had higherincidences of pulmonary complications includingpneumonia, atelectasis, and fever (4). Early postopera-tive ambulation does not appear to influence the dura-tion of ileus, but does appear to decrease other com-

plications related to prolonged immobilization, andthus should be encouraged. Early enteral feeding alsoappears safe, and in some studies has led to decreasedduration of ileus and earlier hospital discharge.

PharmacologicNumerous studies have evaluated the utility of proki-netic agents in POI with mainly disappointing results.Metoclopramide has failed to improve postoperativebowel motility in several randomized trials. Cisaprideshowed promise in some prospective trials but hassince been withdrawn from the U.S. market due to car-diovascular side effects. Erythromycin has been inef-fective in two prospective trials in shortening POI.Domperidone, another prokinetic agent, has not beenevaluated in the postoperative setting and is not cur-rently available in the U.S.

Laxatives are another potential agent for the man-agement of POI. One small, nonrandomized studyreported a reduction in time to flatus and first bowelmovement, as well as decreased length of hospitaliza-tion, compared to historical controls (5). However,larger, randomized trials need to be performed beforethe use of laxatives becomes a routine part of postop-erative patient care.

Nonsteroidal antiinflammatory (NSAID) medica-tions may decrease the duration of POI due to theirantiinflammatory effects, as well as by decreasing theamount of opiates needed for postoperative pain con-trol. Several animal studies suggest the use of NSAIDsmay reduce the duration of POI, but physicians mustbe wary of potential side effects, including antiplateleteffects, increased risk of gastrointestinal bleeding, andadverse renal effects. Cyclooxygenase (COX)-2 selec-tive inhibitors have been reported to be effective inreducing ileus in a recent small study (6), and maydecrease the risk of bleeding associated with the nons-elective COX inhibitors.

Epidural anesthetics have been found to be effec-tive in reducing the duration of POI, possibly byinhibiting sympathetic neural reflexes at the cord leveland by reducing postoperative narcotic use. The loca-tion of the epidural catheter is important, as lumbarepidurals may not effectively block the inhibitory sym-

(continued from page 14)

(continued on page 22)

Table 3 Postoperative ileus: signs and symptoms

Abdominal painNauseaVomitingAnorexiaAbdominal bloatingAbdominal distensionAbsent bowel soundsLack of passage of flatus or stoolTympanic abdomenNo visible peristalsis

PRACTICAL GASTROENTEROLOGY • DECEMBER 200222

A SPECIAL ARTICLE

Postoperative Ileus

(continued from page 17) (continued on page 24)

Table 4 Treatment options for postoperative ileus

Nonpharmacologic treatment options

Treatment Potential Mechanism Comments

Nasogastric tube Gastric/small bowel decompression No evidence NG tubes reduce durationof POI. May increase pulmonary post-operative complications

Early enteral nutrition Stimulates GI motility by eliciting reflex Appears safe, well tolerated. Some, but response and stimulating release of not all, studies suggest decrease in POIseveral hormonal factors

Early mobilization Possible mechanical stimulation No significant change in duration ofPOI, but may decrease other postopcomplications

Laparoscopic surgery Decreased opiate requirements, Most studies find decreased duration of decreased pain, less abdominal wall POI with laparoscopic compared with trauma open surgery

Pharmacologic treatment options

Treatment Potential Mechanism Comments

Metoclopramide Dopamine antagonist, cholinergic agent Majority of RCTs suggest no benefit

Cisapride Dopamine antagonist, cholinergic agonist, Possibly effective; withdrawn from US serotonin receptor agonist market due to arrythmic side effects

Erythromycin Motilin agonist 2 RCTs suggest no benefit

Laxatives Stimulant, prokinetic effects No RCTs. One nonrandomized, unblindedstudy suggests possible benefit

Opiate antagonists Block peripheral opiate receptors One RCT shows ADL8-2698 decreasestime to flatus, BM, hospital discharge,but not currently available outside ofclinical trials. Other agents have notbeen evaluated in POI

Epidural anesthesia Inhibits sympathetic reflex at cord level, Several RCTs suggest benefit in opioid-sparing analgesia decreasing POI; most effective when

inserted at thoracic level

NSAIDs Opiate-sparing analgesia, inhibits Probable benefit. COX-2 selective meds COX-mediated prostaglandin synthesis need further evaluation

Multimodality therapy Combination therapy may work via Possible benefit in reducing POI. No multiple mechanisms RCTs have been reported

PRACTICAL GASTROENTEROLOGY • DECEMBER 200224

A SPECIAL ARTICLE

Postoperative Ileus

pathetic reflexes involved in the pathogenesis of POI,whereas thoracic epidurals should.

Opiate antagonists are an intriguing class of agentsthat have recently been evaluated in the postoperativesetting. Opiate antagonists have been found to improvebowel motility in patients with chronic constipation.More recently, the selective peripherally-acting opiateantagonist ADL8-2698 has been found to significantlyshorten the duration of POI after major abdominalsurgery (7). Other agents, including naloxone andmethylnaltrexone, have not been evaluated in this set-ting but may hold promise.

Several authors have advocated the use of multi-modality therapy to decrease the duration of POI. Thisapproach combines several different potential thera-peutic options, including early mobilization andenteral intake, use of opioid-sparing medications suchas NSAIDs and epidural anesthesia, aggressive laxa-tive use, and avoidance of routine NG tube placement(8). While this may represent a logical treatmentapproach, it requires further study with larger, ran-domized trials before it is routinely incorporated intopostoperative care.

SUMMARYPost-operative ileus is a common sequela of abdominals u rgery that imparts considerable morbidity andexpense to the care of patients, and is a common con-sultation for the practicing gastroenterologist. Despiteits prevalence, the pathophysiology of POI remainsincompletely understood, with sympathetic neuralreflexes and inflammatory mediators likely playingetiologic roles, with exacerbating factors includingdegree of bowel manipulation, opioid analgesia andelectrolyte abnormalities. While non-pharmacologictreatment options such as NG tubes, enteral alimenta-tion and mobilization have historically been utilizedinitially, high-quality data supporting their efficacy is

lacking. Likewise, pharmacologic options includinglaxatives and prokinetic agents also remain withoutstrong data in support of their use. Peripherally actingopioid antagonists and NSAIDs show early promise,but await further trials. ■

References1. Moss G, Regal ME, Lichtig LK. Reducing postoperative pain,

narcotics, and length of hospitalization. Surgery, 1986;90:206-210.

2. Scheinin B, Asantila R, Orko R. The effect of bupivacaine andmorphine on pain and bowel function after colonic surgery. ActaAnaesthesiol Scand, 1987;31:161-164.

3. Kalff JC, Schraut WH, Simmons RL, et al. Surgical manipulationof the gut elicits an intestinal muscularis inflammatory responseresulting in postsurgical ileus. Ann Surg, 1998;228:652-663.

4. Cheatham ML, Chapman WC, Key SP, et al. A meta-analysis ofselective versus routine nasogastric decompression after electivelaparotomy. Ann Surg, 1995;61:1079-1083.

5. Fanning J, Yu-Brekke S. Prospective trial of aggressive postop-erative bowel stimulation following radical hysterectomy.Gynecol Oncol, 1999;73:412-414.

6. Shafiq N, Malhotra S, Pandhi P. Effect of cyclooxygenaseinhibitors in postoperative ileus: an experimental study. MethodsFind Exp Clin Pharmacol, 2002;24:275-278.

7. Taguchi A, Sharma N, Saleem RM, et al. Selective postoperativeinhibition of gastrointestinal opioid receptors. N Engl J Med2001;345:935-940.

8. Basse L, Jakobsen DH, Billesbolle P, et al. A clinical pathway toaccelerate recovery after colonic resection. Ann Surg,2000;232:51-57.

Other Suggested ReadingGeneral

1. Kehlet H, Holte K. Review of postoperative ileus. Am J Surg,2001;182 Suppl:3S-10S.

2. Schuster TG, Montie JE. Postoperative ileus after abdominalsurgery. Urology, 2002; 59:465-471.

Pathophysiology1. Resnick J, Greenwald DA, Brandt LJ. Delayed gastric emptying

and postoperative ileus after nongastric abdominal surgery: PartI. Am J Gastro, 1997;92:751-762.

Treatment1. Bungard TJ, Kale-Pradhan PB. Prokinetic agents for the treat-

ment of postoperative ileus in adults: a review of the literature.Pharmacotherapy, 1999;19:416-423.

2. Resnick J, Greenwald DA, Brandt LJ. Delayed gastric emptyingand postoperative ileus after nongastric abdominal surgery: PartII. Am J Gastro, 1997;92:934-940.

(continued from page 22)

PRAC T IC AL GAS TRO ENT ERO LOG Y