REVIEW ARTICLE

Mechanisms and Treatment of Postoperative Ileus

Andrew Luckey, MD; Edward Livingston, MD; Yvette Taché, PhD

Objective: To review the pathogenesis and treatment
of postoperative ileus.
Data Sources: Data collected for this review were iden-
tified from a MEDLINE database search of the English-
language literature. The exact indexing terms were
“postoperative ileus,” “treatment,” “etiology,” and “patho-
physiology.” Previous review articles and pertinent ref-
erences from those articles were also used.
Study Selection: All relevant studies were included.
Only articles that were case presentations or that men-
tioned postoperative ileus in passing were excluded.
Data Synthesis: The pathogenesis of postoperative il-
eus is complex, with multiple factors contributing ei-
ther simultaneously or at various times during the de-
velopment of this entity. These factors include inhibitory
effects of sympathetic input; release of hormones, neu-
rotransmitters, and other mediators; an inflammatory
reaction; and the effects of anesthetics and analgesics. Nu-
merous treatments have been used to alleviate postop-
erative ileus without much success.
Conclusions: The etiology of postoperative ileus can best
be described as multifactorial. A multimodality treat-
ment approach should include limiting the administra-
tion of agents known to contribute to postoperative il-
eus (narcotics), using thoracic epidurals with local
anesthetics when possible, and selectively applying na-
sogastric decompression.
Arch Surg. 2003;138:206-214

From the University of
California at San
Francisco–East Bay, Oakland
(Dr Luckey); the Departments
of Surgery (Dr Livingston) and
Medicine (Dr Taché), The
David Geffen School of
Medicine, and the Bariatric
Surgery Program
(Dr Livingston), University of
California at Los Angeles, and
CURE: Digestive Diseases
Research Center, VA Greater
LA Healthcare System,
Los Angeles (Dr Taché).
I
LEUS IS DEFINED in Dorland’s Illus-
trated Medical Dictionary simply as
“obstruction of the intestines.”1
However, the definition of post-
operative ileus, the topic of this re-
view, is a bit less clear. In 1990, Living-
ston and Passaro2 defined ileus as “the
functional inhibition of propulsive bowel
activity, irrespective of pathogenetic mecha-
nisms.” They further defined postopera-
tive ileus as the “uncomplicated ileus oc-
curring following surgery, resolving
spontaneously within 2 to 3 days.” Fi-
nally, the term paralytic postoperative ileus
was defined as that form of ileus lasting
more than 3 days after surgery.2 Such a dis-
tinction was necessary because different
mechanisms are probably responsible for
the 2 types of postoperative ileus. It may
be more correct to call postoperative ileus
a primary ileus in that it is most likely an
inevitable response to surgical trauma. In
postoperative ileus, inhibition of small-
bowel motility is transient, and the stom-
ach recovers within 24 to 48 hours, whereas
colonic function takes 48 to 72 hours to re-
turn.2 Determination of the end of postop-
erative ileus is somewhat controversial. The
studies in the literature have used varying
end points, and each has its own weak-
ness. Bowel sounds are sometimes used as
an end point, but they require frequent aus-
cultation, their presence does not neces-
sarily indicate propulsive activity, and they
can be the result of small-bowel activity and
not colonic function.3 Flatus also is not the
ideal end point. It requires a conscious pa-
tient who is comfortable reporting its oc-
currence to the investigator. Also, there is
some question as to the correlation be-
tween flatus and bowel movements.4 Bowel
movements are seemingly the most reli-
able end point, although they too may be
nonspecific, representing distal bowel
evacuation as opposed to global gastrointes-
tinal tract function. In the end, the health
care provider should assess the patient as
a whole to determine the resolution of post-
operative ileus.
HISTORY
The reduction in bowel motility after sur-
gery has been described since the late 1800s.
A multiplicity of studies have been pub-
lished on postoperative ileus, but the patho-
genesis remains an enigma (Table 1). Little
advancement in effective treatment regi-

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 mens has taken place since the introduction of nasogas-
tric decompression. Ileus is a significant medical problem
and constitutes the most common reason for delayed dis-
charge from the hospital after abdominal surgery. The eco-
nomic impact of ileus has been estimated to be $750 mil-
lion to $1 billion in the United States.5 More important
than health care costs is patient discomfort. The symp-
toms of postoperative ileus range from cramping and ab-
dominal pain to nausea and vomiting.
The presence of inhibitory spinal reflexes acting on
the bowel was first demonstrated in 1872 by Goltz.6 In
1899, Bayliss and Starling7 determined that the ablation
of splanchnic nerves would improve bowel motility af-
ter laparotomy. They discovered this by using a device
termed the enterograph, which allowed them to study in-
tact small-intestinal activity in the unanesthetized dog.7
During the past few decades, numerous reports have been
published reaffirming the implication of sympathetic path-
ways in postoperative ileus. Over the years, experimen-
tal models of postoperative ileus have been developed to
assess propulsive bowel motor function. Some of these
models include gastric emptying, small- and large-bowel
transit time, and stool pellet output as well as recording
changes in bowel motility.8-14 An experimental model us-
ing strain gauge transducers in awake rats has been re-
ported15 as a method of measuring gastrointestinal mo-
tility. Many new theories have been hypothesized to
explain the pathogenesis of postoperative ileus.
NORMAL PHYSIOLOGY
OF GASTROINTESTINAL MOTILITY
Normal bowel motility results from complex interactions
among the enteric nervous system, central nervous sys-
tem, hormones, and local factors affecting smooth-
muscle activity. Motility in the stomach and small intes-
tine varies based on whether one is in the fasting or fed
state. Compared with fasting, the fed pattern consists of
continuous low varying-amplitude, ungrouped contrac-
tions whose number, intensity, and duration depend on
the food ingested (amount and physical and chemical
composition). However, between meals, the migrating mo-
tor complex (MMC) dictates the contractile pattern of the
bowel. The MMC, first described by Szurszewski,16 is be-
lieved to serve a “housekeeper” function by propelling in-
traluminal contents distally during the fasting state.17 In
humans, these contractions occur approximately once ev-
ery 1 to 2 hours.
Four phases are involved in the MMC in the fasted
state. The first phase includes oscillating smooth-
muscle membrane potentials without actual muscle
contractions. The occurrence of intermittent muscle
contractions marks the transition to phase II. During
phase III, the contractions increase to the maximal con-
tractile frequency allowed by the slow wave (approxi-
mately 3 contractions per minute in the stomach and 11
contractions per minute in the duodenum). Phase IV is
marked by cessation of contractions, and the bowel be-
comes quiescent.18 Feeding is followed by interruption
of the MMC and the appearance of a different pattern
consisting of sustained irregular phasic contractile
activity.
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Table 1. Possible Mechanisms of Postoperative Ileus
Mechanisms Factors Involved
Autonomic nervous system Sympathetic inhibitory pathways
Enteric nervous system Substance P, nitric oxide
Hormones and Vasoactive intestinal peptide;
neuropeptides corticotropin-releasing factor ligands;
calcitonin gene−related peptide
ligands
Inflammation Macrophage and neutrophil infiltration;
cytokines, other inflammatory
mediators
Anesthesia General anesthetics
Narcotics Opiates
The musculature of the stomach is made of cells that
are intimately associated, allowing them to conduct elec-
trophysiologic functions. There are 3 distinctive electri-
cal potentials: resting potential; slow-wave or pacesetter
potential; and spike potential19 that trigger contractions.
However, these potentials can only occur during the slow-
wave frequency and thus are determined by the pace-
maker. Numerous gastrointestinal hormones affecting
gastrointestinal motility have been reviewed recently,20 and
a detailed discussion of this topic is beyond the scope of
this review. Gastric motility is thus determined by com-
plex interactions among the electrophysiologic character-
istics, neural input, and gastrointestinal hormones.
The colon, whose main purpose is to absorb water
and store feces, differs in structure and function from the
remainder of the bowel. Measured electrical activity in
the colon reveals irregular oscillations with varying am-
plitude. Colonic smooth muscle does not contain gap
junctions and therefore does not act as a single unit. In
humans, 3 electrical activities of colonic motility can be
distinguished: electrical control activity represents
smooth-muscle membrane potential oscillations, dis-
crete electrical response activity consists of spike-wave
potentials superimposed on the oscillations, and con-
tinuous electrical response activity is not related to os-
cillations but is involved with contractions that sweep
luminal contents distally.21
PATHOGENESIS
Altered Gastrointestinal Motility
in Postoperative Ileus
In the stomach and the small intestines, normal basal elec-
trical activity is impaired after surgical procedures. Spe-
cifically, in the stomach there is an irregular pattern of
gastric spike and slow-wave activity. In addition, after
surgery, if patients are not being fed, MMC activity is
thought to be the “only impetus to bowel contraction.”2
Therefore, patients who are restricted from taking any-
thing by mouth after surgery are also thought to have
minimally propulsive bowel motility. Various anes-
thetic agents can affect MMC activity. For example, ether
and halothane are inhibitory, whereas enflurane is exci-
tatory.22,23 Incising the peritoneum likewise inhibits MMC
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 activity, and prolonged inhibition is observed after bowel
manipulation.2
The colon’s electrical activity is also disturbed as a re-
sult of surgical procedures. After surgery in monkeys and
humans, there is disruption of the 3 electrical activities de-
scribed in the previous section.24,25 Continuous electrical
response activity is the last to return to normal (approxi-
mately 72 hours after surgery) and is associated with the
onset of flatus. Although the electrical activity of the gas-
trointestinal tract is disturbed in patients with paralytic post-
operative ileus, the return of normal electrical activity does
not always coincide with resolution of the ileus.
The Role of the Autonomic Nervous System
A balance exists between excitatory and inhibitory input
in the regulation of bowel motility. Parasympathetic stimu-
lation increases gastrointestinal motility, whereas sympa-
thetic stimulation is inhibitory. Sympathetic input serves
as the predominant inhibitory impetus to the bowel and
provides the efferent limb of numerous reflex pathways.
Supporting evidence for this concept is based on animal
experiments26 that demonstrated the predominance of sym-
pathetic inhibition following division of the parasympa-
thetic (vagal) and sympathetic (splanchnic) neural in-
put. Previous studies have demonstrated sympathetic
output as a factor in the pathogenesis of postoperative il-
eus. The mechanism of sympathetic inhibition involves
preventing the release of acetylcholine from excitatory fi-
bers located in the myenteric plexus. Small-bowel post-
operative ileus and delayed gastric emptying are ablated
using chemical sympathectomy with 6-hydroxydopam-
ine.27,28 In addition, intestinal catecholamine stores are de-
pleted more rapidly after laparotomy vs no laparotomy.29
However, sympathetic blockade is not always suc-
cessful in reversing the inhibition of gastrointestinal mo-
tility induced by abdominal surgical procedures.30 Thus,
other mechanisms, such as nonadrenergic noncholin-
ergic nerves, are believed to play a role in inhibiting gut
motility after surgery.
The Role of Neurotransmitters,
Local Factors, and Hormones
A variety of neurotransmitters, local factors, and hor-
mones has been proposed to contribute to postoperative
ileus, although no single factor has been clearly proven
to be responsible. Vasoactive intestinal peptide causes an
increase in inhibitory input to the gastric cholinergic neu-
rons, creating a decrease in antral and pyloric activity.31
Substance P, which is a neurotransmitter involved in pain,
has also been hypothesized to have a role in postopera-
tive ileus.32
Nitric oxide (NO) is believed to be the predominant
inhibitory nonadrenergic noncholinergic neurotransmit-
ter of the gastrointestinal tract. It is thought to act through
its constitutive form of NO synthetase within enteric neu-
rons.33 Researchers30,34 have examined the role of NO in a
rat model of postoperative ileus. Rats were assigned to un-
dergo a skin incision, laparotomy only, or laparotomy,
evisceration, and manipulation of the cecum and small
intestine. Reserpine, an inhibitor of adrenergic neurotrans-
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mission, and N␻-nitro-L-arginine, an NO synthase inhibi-
tor, were given alone and in combination. When given
alone, reserpine significantly increased gastrointestinal tran-
sit in rats that underwent a skin incision, completely re-
versed the inhibition caused by laparotomy alone, but only
partially reversed the inhibition of transit induced by lap-
arotomy, evisceration, and manipulation. In contrast, N␻-
nitro-L-arginine administration had no effect on gas-
trointestinal transit altered by the skin incision or by
laparotomy only and partially reversed the negative ef-
fects on motility caused by laparotomy, evisceration, and
manipulation. Given in combination, these drugs showed
no additional effects over reserpine therapy alone in the
skin incision and laparotomy-only groups; however, ad-
ministration of these drugs resulted in a complete rever-
sal of the inhibition of gastrointestinal motility induced
by laparotomy, evisceration, and manipulation. These re-
sults support the involvement of NO release in postop-
erative ileus. The role of NO in the pathogenesis of post-
operative ileus in humans remains unclear. Experimental
evidence13,35 has shown that antagonists to vasoactive in-
testinal peptide, substance P, and inhibitors of NO syn-
thesis improve postoperative bowel motility.
Calcitonin gene–related peptide (CGRP) is present
in visceral afferent neurons in the gastrointestinal tract and
acts on peripheral receptors to delay gastric emptying and
gastrointestinal motility in rats.14,36 It is possible that ab-
dominal surgical procedures stimulate the release of CGRP
from these neurons, causing inhibition of bowel motility.
The administration of CGRP receptor antagonists or mono-
clonal antibodies to CGRP has been shown36 to partially
prevent postoperative gastric ileus in rats.
Endogenous opioids are released after surgery and
have been suggested as a cause of postoperative il-
eus.37,38 Their effects on gastric emptying and intestinal
smooth-muscle contraction are mediated by the µ-opioid
receptor. Enkephalin is a potent ␦-opioid receptor ago-
nist that has been reported to inhibit gastric motility and
increase pyloric tone in animal experiments.39,40
Corticotropin-releasing factor (CRF) is instrumen-
tal in orchestrating the stress response.41,42 A previous study
by Taché et al43 has shown that the peripheral adminis-
tration of CRF and CRF-related peptides induces a delay
in gastric emptying and an inhibition of gastric motility
similar to that seen in postoperative gastric ileus. Periph-
eral CRF decreases gastric emptying of a nonnutrient or
nutrient meal in rats, mice, and dogs when administered
intravenously. Similar effects are seen in rats and mice if
the CRF or CRF-related peptides are injected intraperito-
neally or subcutaneously.10,44-50 Furthermore, peripheral
injection of a nonselective CRF receptor antagonist be-
fore laparotomy and cecal palpation completely allevi-
ates postoperative gastric ileus assessed during the first 3
hours after surgery in rats.47,51 In humans, surgical stress
has been associated with an elevation in circulating levels
of CRF.52-54 The source of the CRF is unclear. The pep-
tide is present in the adrenal medulla, and splanchnic nerves
and hormonal stimulation can trigger its release.55,56 Spe-
cifically, arginine vasopressin that is released in response
to surgical stress can trigger CRF release. Studies are on-
going to elucidate the mechanisms by which CRF inhib-
its gastric emptying.
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 The Role of Inflammation
In 1998, Kalff et al57 hypothesized that common surgical
procedures performed on the intestine elicit activation of
the macrophage network in the muscularis externa and
generate leukocyte recruitment. He further proposed that
this inflammatory reaction is responsible for a period of
postoperative dysmotility.57 In this study, rats were ex-
posed to varying degrees of “gentle” surgical manipula-
tion, ranging from a midline laparotomy to “running” of
the bowel. Rats that were not subjected to laparotomy or
anesthesia served as age-matched controls. The results sup-
ported their hypothesis in that a progressive increase in
neutrophil infiltration was seen with increasing degrees
of bowel manipulation. The authors concluded that their
data support the belief that an inflammatory event initi-
ated by abdominal surgical procedures is associated with
postoperative ileus. However, they also conceded that extra-
abdominal, surgically induced postoperative ileus is caused
by another mechanism.
Schwarz et al58 found an induction of cyclooxy-
genase 2 (COX-2) messenger RNA and protein in resi-
dent macrophages and a subpopulation of enteric neu-
rons after laparotomy and intestinal manipulation in rats.
The increase in COX-2 expression resulted in elevated
levels of prostaglandins in the peritoneal cavity and the
circulation. As a result, decreased jejunal circular muscle
contractility was observed in vitro. This effect could be
reversed with administration of COX-2 inhibitors. Cli-
nicians should be cautious in applying this model to hu-
mans. Although in rats the small intestine is said to serve
as a good model for postoperative ileus, the same does
not hold true for humans. It would be worthwhile to in-
vestigate the effects of COX-2 inhibition on postopera-
tive gastric and colonic motility.
ANESTHESIA
All types of anesthesia have an effect on bowel motil-
ity.59 Anesthetic agents exert their strongest effects on the
region of the bowel that depends most on neural inte-
gration. Most notably, the large intestine is devoid of in-
tercellular gap junctions, which makes the colon more
susceptible to the inhibitory actions of anesthetics.2
Delayed gastric emptying is observed after expo-
sure to anesthesia. Atropine, halothane, and enflurane
all decrease gastric emptying. The consequences of de-
layed gastric emptying are possible aspiration, in-
creased risk of postoperative nausea and vomiting, and
delayed absorption of medications.60-62
In theory, epidurals with local anesthetics can block
afferent and efferent inhibitory reflexes, increase splanch-
nic blood flow, and have anti-inflammatory effects.63,64 Epi-
dural anesthetics have the added benefit of blocking the
afferent stimuli that trigger the endocrine metabolic stress
response to surgery and thus inhibit the catabolic activity
of hormones released during this process.65 In most stud-
ies,66-76 thoracic epidurals with bupivacaine hydrochlo-
ride significantly reduced ileus vs systemic opioid therapy
in patients undergoing abdominal surgical procedures. In
one of the statistically nonsignificant studies,64 an epidu-
ral anesthesia of 24-hours’ duration was used as opposed
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to that of 48 to 72 hours’ duration, as used in other stud-
ies. At least 4 studies67,72,74,75 have compared epidural bupiv-
acaine with epidural opioid, and 3 of these studies dem-
onstrated a significant reduction in the duration of
postoperative ileus in the epidural bupivacaine group com-
pared with the epidural opioid group. Of the few prospec-
tive studies72,74,76 comparing the effects of epidural bupiv-
acaine and combined epidural bupivacaine and morphine
on recovery from postoperative ileus, epidural bupiv-
acaine alone seems to be superior without significantly ad-
versely affecting pain relief. The location of the epidural
is important; low-thoracic and lumbar epidural adminis-
tration has not been shown64,72,73,77,78 to have beneficial ef-
fects on postoperative ileus.
POSTOPERATIVE NARCOTIC ANALGESIA
Opioids have an inhibitory effect on gastric motility and
also increase tone in the antrum and the first portion of
the duodenum in healthy individuals.79 The effects of opi-
ates on the small intestine are slightly more compli-
cated. Morphine sulfate has biphasic properties in hu-
mans: (1) initial effects on motility are stimulatory via
activation of MMC phase III, and (2) this stimulation is
followed by atony, which is responsible for the slowing
of gastrointestinal transit.79,80 Morphine increases the tone
and amplitude of nonpropulsive contractions and de-
creases propulsive waves in the colon. The additive ef-
fect of these actions is to decrease colonic motility.79
However, treatment with the morphine receptor an-
tagonist naloxone hydrochloride has proven ineffective
in the treatment of postoperative ileus.2 New µ-opioid
receptor antagonists are being developed and may have
the potential to alleviate opiate-related adverse effects.
Methylnaltrexone bromide, a quaternary derivative of nal-
trexone, is one such drug. It is poorly lipid soluble and
therefore does not cross the blood-brain barrier, but it
can inhibit the negative effects of opioids on the gut. As
a result, it does not antagonize the central analgesic ef-
fects of morphine or initiate opioid withdrawl.81 An-
other drug being investigated is the µ-opioid receptor an-
tagonist ADL-8-2698. Administration of 6 mg of this drug
shortened the median time to passage of first flatus, the
median time to the first bowel movement, and the length
of hospital stay in a study82 of 79 patients, of which 15
underwent partial colectomy and 63 underwent total ab-
dominal hysterectomy. Other experimental studies37 in-
dicate that opioid agonists working at the ␬ receptor may
be beneficial by serving as an analgesic and decreasing
postoperative ileus. Questions remain about the role of
these agents in patients not treated with opioids for post-
operative pain and about whether the beneficial effects
of these agents are seen in patients undergoing other sur-
gical procedures.
TREATMENTS
Nasogastric Intubation
For many years, the nasogastric tube has been the
mainstay of treatment; however, recent studies have
questioned its routine use. These randomized clinical stud-
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 ies83,84 conclude that nasogastric decompression does not
shorten time to first bowel movement or decrease time
to adequate oral intake. Furthermore, these studies83,84
report that inappropriate use may contribute to postop-
erative complications such as fever, pneumonia, and
atelectasis. Although these studies do not recommend rou-
tine use of nasogastric intubation, the clinician may have
selected cases in which the patient benefits from symp-
tomatic relief.
Electrical Stimulation
Given the previous descriptions of abnormal gastrointes-
tinal electrical activity, efforts have been made to use elec-
trical stimulation as a corrective measure. An attempt has
been made to apply electrical stimulation directly to the
bowel wall in dogs, but this procedure was not success-
ful.85 Other studies show that using gastrointestinal pac-
ing in humans is largely ineffective.2
Early Postoperative Feeding
Early postoperative enteral feeding via oral or nasoen-
teric administration has been suggested as a way to de-
crease the duration of postoperative ileus. The logic be-
hind early enteral feeding is that food intake can (1)
stimulate a reflex that produces coordinated propulsive
activity and (2) elicit the secretion of gastrointestinal hor-
mones, causing an overall positive effect on bowel mo-
tility.86 The role of early postoperative enteral feeding re-
mains unclear because some studies support and others
refute its benefit on shortening postoperative ileus.87-91
Laparoscopic Procedures
Laparoscopic procedures offer the theoretical advan-
tage of decreased tissue trauma compared with open pro-
cedures. This decrease in tissue trauma may lead to faster
recovery of postoperative bowel function. Recently, Leung
et al92 found lower levels of cytokines (interleukin 1␤ and
interleukin 6) and C-reactive protein in patients under-
going laparoscopic colon resection compared with those
who had open procedures. Animal studies and clinical
trials93-96 have found statistically significant decreases in
the duration of postoperative ileus after laparoscopic vs
open procedures for colon resection. The exact mecha-
nism responsible for this improvement in postoperative
bowel motility remains elusive. Ongoing research may
answer this question and give insight into the etiology
of paralytic ileus after open procedures.
Pharmacologic Agents
Nonsteroidal anti-inflammatory drug therapy may im-
prove postoperative ileus by allowing the clinician to re-
duce the amount of opioid given by 20% to 30%.97 An
additional benefit on bowel motility may be derived from
the anti-inflammatory properties of nonsteroidal anti-
inflammatory drugs.98 In most experimental and clini-
cal studies,99-102 giving nonsteroidal anti-inflammatory
drugs resulted in decreased nausea and vomiting and im-
proved gastrointestinal transit.
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Many clinicians use laxatives as a treatment for para-
lytic postoperative ileus. No randomized trials evaluat-
ing the role of these agents in paralytic postoperative il-
eus have been conducted, to our knowledge. Conducting
a MEDLINE database search for the key words “laxa-
tives” and “postoperative ileus,” only 1 nonrandom-
ized, unblinded trial was found. This trial consisted of
20 patients who underwent radical hysterectomy and were
postoperatively treated with 30 mL of milk of magnesia
by mouth twice daily and biscolic suppositories every
day.103 The median time to flatus and bowel movement
was 3 days. The authors observed a 50% reduction in the
length of hospital stay vs a group of patients from a pre-
viously reported prospective study103 of patients under-
going radical hysterectomy (4 vs 8 days). This study
should be followed by a randomized, prospective, double-
blind, controlled study to determine the benefit, if any,
of using laxatives.
Prostaglandins are known to affect bowel motility.
The mechanism of prostaglandin E2 and prostaglandin
F2, although not entirely clear, seems to be the stimula-
tion of acetylcholine release from myenteric plexus neu-
rons.104 In humans, oral prostaglandin E2 is reported to
increase small intestine and colonic transit.2 Further stud-
ies are needed to determine whether there is clinical ben-
efit from prostaglandins.
Sympathetic inhibitory input is thought to play a role
in the pathogenesis of postoperative ileus.27,28 Thus, based
on existing experimental evidence, human studies at-
tempting to induce adrenergic inhibition and cholinergic
activation were conducted. These studies105 did not dem-
onstrate resolution of postoperative ileus. Studies106,107 us-
ing edrophonium chloride and bethanechol chloride have
reported improvement in postoperative ileus in humans,
but the adverse effects of these agents limit their use.
Acetylcholine is released from the enteric nervous
system and causes increased gut wall contractility.108
Acetylcholine is degraded in the synaptic cleft by acetyl-
cholinesterase. Neostigmine is a reversible inhibitor of
acetylcholinesterase and as such has been investigated
as a potential treatment for postoperative ileus. Kreis et
al109 recently found that neostigmine therapy signifi-
cantly increased colonic motility in the early postopera-
tive period in patients undergoing colorectal surgery. These
results are encouraging, but the “early postoperative pe-
riod” is most likely a physiologic ileus, and experiments
to determine the effect of neostigmine use on paralytic
ileus should be performed.
Metoclopramide hydrochloride is a prokinetic agent
that acts as a cholinergic agonist and a dopamine antago-
nist. It initiates MMC phase III activity via its antagonis-
tic actions on dopamine. At least 6 controlled clinical tri-
als105-111 have investigated the effect of metoclopramide
therapy on patients undergoing abdominal surgical pro-
cedures. Although the end points used in the studies dif-
fered, none of them had a significant benefit in the treat-
ment of postoperative ileus.110-116
Erythromycin is a 13-carbon antibiotic belonging to
the macrolide family. The gastrointestinal adverse ef-
fects induced by this antibiotic include abdominal cramp-
ing, nausea, vomiting, and diarrhea. Erythromycin is a
motilin receptor agonist that binds to gastrointestinal
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 smooth-muscle membrane receptors, displacing the en-
dogenous ligand motilin. Erythromycin therapy did not
resolve postoperative ileus in patients who underwent
abdominal surgery in the prospective, randomized clini-
cal trials conducted.117,118
Cisapride is a serotonin agonist that facilitates
acetylcholine release from the intrinsic plexus. At least
9 randomized clinical trials119-127 have been performed on
patients treated with cisapride for postoperative ileus af-
ter undergoing various surgical procedures. However,
comparison of these studies is difficult because various
end points were used, patients underwent different sur-
gical procedures, and the doses, durations, and routes were
variable. In 4 studies,119-122 there was a statistically sig-
nificant reduction in postoperative ileus. Although these
results are encouraging, just as many studies123,126,127 re-
ported no statistically significant effects. The questions
regarding the effectiveness of cisapride will remain as it
has been removed from the market for deleterious side
effects.
Ceruletide is a synthetic peptide that may enhance
gastrointestinal motility by acting as a cholecystokinin
antagonist.1 A slight reduction in ileus was noted in 2 clini-
cal placebo-controlled studies.128,129 Ceruletide therapy
has the adverse effects of nausea and vomiting, which may
limit its clinical effectiveness. Further investigation is
needed before clinical use can be recommended.
Octreotide is an analogue of somatostatin that is
known to inhibit the secretion of many gastrointestinal
hormones. Cullen et al130 showed that octreotide therapy
shortens the duration of ileus in the small intestine and
colon of dogs. However, clinical studies are needed to
prove its efficacy in humans.
Other Treatments
Gum chewing may be a simple but effective treatment
for postoperative ileus. Asao et al131 conducted a ran-
domized, prospective, controlled study on gum chew-
ing as a method to stimulate bowel motility after laparo-
scopic colectomy for colorectal cancer. The patients
chewed gum 3 times a day starting postoperative day 1
until oral intake. The passage of first flatus was on aver-
age 1.1 days earlier in the gum-chewing group than in
controls (day 2.1 vs 3.2). The first defecation also was
significantly earlier in the gum-chewing patients (post-
operative day 3.1) than in controls (postoperative day 5.8).
However, the length of hospital stay was not signifi-
cantly different between the 2 groups (13.5 vs 14.5 days)
and overall was somewhat longer than that reported in
the literature. The authors hypothesize that the aid in re-
covery from postoperative ileus achieved by gum chew-
ing may be related to the effects of sham feeding. Sham
feeding causes vagal cholinergic stimulation of the gas-
trointestinal tract and elicits the release of gastrin, pan-
creatic polypeptide, and neurotensin, all of which affect
gastrointestinal motility.132,133 Further prospective, ran-
domized controlled studies on the effect of gum chew-
ing on postoperative bowel motility are warranted.
Lobo et al134 wanted to determine the effect of water
and salt balance on the recovery of gastrointestinal tran-
sit in patients undergoing colonic resection for colon can-
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cer. Their study design randomly assigned patients to re-
ceive a standard postoperative fluid regimen (3 L of water
and 154 mmol of sodium per day) or a restricted fluid pro-
tocol (ⱕ2 L of water and 77 mmol of sodium per day).
The primary end points of the study included solid- and
liquid-phase gastric emptying as measured by isotope ra-
dionuclide scintigraph on the fourth postoperative day, with
first flatus and bowel movement serving as secondary end
points. The results demonstrated significantly longer solid
and liquid gastric emptying for the standard group vs the
restricted fluid group (solid: 175 vs 72 minutes; liquid: 110
vs 73 minutes). Patients receiving restricted fluids passed
first flatus 1 day earlier, had the first bowel movement 2.5
days earlier, and had a 3-day shorter median length of stay
in the hospital than patients receiving standard fluid vol-
umes (P=.001 for all). The authors concluded that a posi-
tive salt and water balance significant enough to add 3 kg
of body weight after colonic resection delays gastrointes-
tinal transit and prolongs hospital stay.
The Multimodel Approach to Postoperative Ileus
Of all the treatments available (Table 2), which is best?
The best treatment currently available is a multimodal
regimen. Basse et al135 examined a multimodal rehabili-
tation regimen for the treatment of postoperative ileus
consisting of continuous epidural analgesia, early oral nu-
trition and mobilization, and cisapride and laxative treat-
ment with magnesia. Using this regimen, the authors ob-
served normalization of gastrointestinal transit time within
48 hours of colonic resection compared with matched
controls. Gastrointestinal transit time was assessed by an
indium In 111 pentetate scintigraphic method. The rela-
tive contribution of each modality is unknown. This par-
ticular approach is less than ideal, given that cisapride
is no longer available. Also, ambulation has not been
shown to improve postoperative bowel motility, al-
though it is beneficial to patients for other reasons.136
Another study137 supporting the multimodal ap-
proach was conducted on patients undergoing segmental
colectomy. The authors used a regimen that included tho-
racic epidural anesthesia for 48 hours, omission of a na-
sogastric tube, 1 L of fluid orally on the day of surgery, mo-
bilization within 8 hours of surgery, use of milk of magnesia,
and an alteration in the incision (curved or transverse) to
minimize pain and pulmonary dysfunction. Ninety-five of
100 patients evaluated defecated in 48 to 72 hours.
SUMMARY
Paralytic postoperative ileus continues to be a significant
clinical problem. The etiology of this process can best be
described as multifactorial. These factors act simulta-
neously or at various times during the development of post-
operative ileus. The mechanisms involved in paralytic post-
operative ileus include inhibitory sympathetic input; release
of hormones, neurotransmitters, and other mediators; an
inflammatory reaction; and the effects of analgesics. Ex-
perimental studies continue to elucidate the roles and
mechanisms of action of all of these factors. Numerous
methods have been used in an attempt to alleviate post-
operative ileus in the clinical setting, without much suc-
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 Table 2. Treatments for Postoperative Ileus

Treatments Benefits Drawbacks

Nasogastric tube • Possible relief of vomiting and bloating • Do not shorten duration of ileus
• May contribute to fever and atelectasis
Early postoperative feeding • Stimulates reflex for propulsive bowel motility • Data not conclusive
• Earlier hospital discharge • Patients may not tolerate feeding
Laparoscopic procedures • Earlier return of bowel function and earlier hospital • Not all surgical procedures are amenable to the
discharge laparoscopic approach
Local epidural anesthetic/analgesics • Reduced duration of ileus vs epidural and systemic • Complications associated with epidural catheters
morphine
• Increases splanchnic blood flow
• Blocks afferent and efferent sympathetic inhibitory
input
• Anti-inflammatory
Gum chewing • May shorten the duration of ileus • Only one small trial that was limited to
• Simple and inexpensive laparoscopic colectomy
Laxatives • May shorten the duration of ileus • Clinical data proving effectiveness/lacking
• Inexpensive
Nonsteroidal anti-inflammatory • Decreased amount of opioid needed for • Possible increased risk of postoperative bleeding
drugs postoperative pain management • Other adverse effects associated with these agents
• May increase motility by acting as an
anti-inflammatory

cess. At this time, it is best to recommend an approach that
will decrease factors contributing to paralytic postopera-
tive ileus. This approach would include limiting the ad-
ministration of narcotics and using alternative analgesics
such as nonsteroidal anti-inflammatory drugs and plac-
ing a thoracic epidural with local anesthetics when pos-
sible. Selective use of nasogastric decompression and the
correction of electrolyte imbalances are also important in
the multimodal approach to the treatment of paralytic post-
operative ileus. Ongoing research can have a positive im-
pact in areas such as selective opioid antagonist, laparo-
scopic surgery, and the manipulation of local factors,
neurotransmitters, and stress hormones. Clinicians look
forward to the day when paralytic postoperative ileus is
an entity of the past.
Corresponding author and reprints: Andrew Luckey, MD,
The David Geffen School of Medicine at the University of
California at Los Angeles, CURE: Digestive Diseases Re-
search Center, VA Greater LA Healthcare System, 11301
Wilshire Blvd, Building 115, Room 217, Los Angeles, CA
90073 (e-mail: LuckeyA@surgery.uscf.edu).
REFERENCES
1. Dorland’s Illustrated Medical Dictionary. 28th ed. Philadelphia, Pa: WB Saun-
ders Co; 1994:819.
2. Livingston EH, Passaro EP. Postoperative ileus. Dig Dis Sci. 1990;35:121-131.
3. Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg. 2000;
87:1480-1493.
4. Waldhausen JH, Shaffrey ME, Skenderis BS II, Jones RS, Schirmer BD. Gas-
trointestinal myoelectric and clinical patterns of recovery after laparotomy. Ann
Surg. 1990;211:777-784.
5. Moss G, Regal ME, Lichtig LK. Reducing postoperative pain, narcotics and length
of hospitalization. Surgery. 1986;90:206-210.
6. Neely J, Catchpole B. Ileus: the restoration of alimentary tract motility by phar-
macological means. Br J Surg. 1971;58:21-28.
7. Bayliss WM, Starling EH. The movements and innervations of the small intes-
tine. J Physiol (Lond). 1899;24:99-143.
8. Dubois A, Henry D, Kopin I. Plasma catecholamines and postoperative gastric
emptying and small intestinal propulsion in the rat. Gastroenterology. 1975;
68:466-469.
9. Sargrada A, Fargeas MJ, Bueno L. Involvement of alpha-1 and alpha-2 adreno-
receptors in the postlaparotomy intestinal motor disturbances in the rat. Gut.
1987;28:955-959.
10. Barquist E, Zinner M, Rivier J, Taché Y. Abdominal surgery–induced delayed
gastric emptying in rats: role of CRF and sensory neurons. Am J Physiol. 1992;
262:G616-G620.
11. Zittel TT, Reddy NS, Plourde V, Raybould HE. Role of spinal afferents and cal-
citonin gene–related peptide in the postoperative gastric ileus in anesthetized
rats. Ann Surg. 1994;219:79-87.
12. Riviere JM, Pascaud X, Chevalier E, Le Gallou B, Junien JL. Fedotozine re-
verses ileus induced by surgery or peritonitis: action at peripheral ␬-opioid re-
ceptors. Gastroenterology. 1993;104:724-731.
13. Espat NJ, Cheng G, Kelley MC, Vogel SB, Sninsky CA, Hocking MP. Vasoactive
intestinal peptide and substance P receptor antagonists improve postoperative
ileus. J Surg Res. 1995;58:719-723.
14. Zittel TT, Lloyd KCK, Tothenhofer I, Wong H, Walsh JH, Raybould HE. Calcito-
nin gene–related peptide and spinal afferents partly mediate postoperative co-
lonic ileus in the rat. Surgery. 1998;123:518-527.
15. Huge A, Kreis ME, Jehle EC, et al. A model to investigate postoperative ileus
with strain gauge transducers in awake rats. J Surg Res. 1998;74:112-118.
16. Szurszewski JH. A migrating electric complex of the canine small intestine. Am
J Physiol. 1969;217:1757-1763.
17. Code CF, Schlegel J. The gastrointestinal interdigestive housekeeper: motor cor-
relate of the interdigestive myoelectric complex of the dog. In: Daniel EE, ed.
Proceedings of the Fourth International Symposium on GI Motility. Vancouver,
British Columbia: Mitchell Press; 1973.
18. Sarna SK. Cyclic motor activity; migrating motor complex: 1985. Gastroenter-
ology. 1985;89:894-913.
19. Hocking MP, Vogel SB. Physiology of gastric secretion and motility in normal
and postgastrectomy (post vagotomy) states. In: Hocking MP, Vogel SB, eds.
Woodward’s Postgastrectomy Syndromes. 2nd ed. Philadelphia, Pa: WB Saun-
ders Co; 1991:29-46.
20. Fujimiya M, Inui A. Peptidergic regulation of gastrointestinal motility in ro-
dents. Peptides. 2000;21:1565-1582.
21. Sarna SK, Bardakjian BE, Waterfall WE, Lind JF. Human electrical control ac-
tivity (ECA). Gastroenterology. 1980;78:1526-1536.
22. Bueno L, Ferre JP, Ruckebusch Y. Effects of anesthesia and surgical procedures
on intestinal myoelectric activity in rats. Am J Dig Dis. 1978;23:690-695.
23. Marshall FN, Pittenger CB, Long JP. Effects of halothane on gastrointestinal mo-
tility. Anesthesiology. 1961;22:363-366.
24. Condon RE, Cowles VE, Schulte WJ, Frantzides CT, Mahoney JL, Sarna SK. Reso-
lution of postoperative ileus in humans. Ann Surg. 1986;203:574-581.
25. Woods JH, Erickson LW, Condon RE, Schulte WJ, Sillin LF. Postoperative il-
eus: a colonic problem? Surgery. 1978;84:527-533.
26. Kenwenter J. The vagal control of duodenal and ileal motility and blood flow.
Acta Physiol Scand. 1965;63:1-68.
27. Nilsson F, Jung B. Gastric evacuation and small propulsion after laparotomy.
Acta Chir Scand. 1973;139:724-730.

(REPRINTED) ARCH SURG/ VOL 138, FEB 2003 WWW.ARCHSURG.COM

212

©2003 American Medical Association. All rights reserved.

Downloaded From: http://archsurg.jamanetwork.com/ by a University of Alabama-Birmingham User on 01/01/2013
 28. Dubois A, Weise VK, Kopin IJ. Postoperative ileus in the rat: physiology, etiol-
ogy and treatment. Ann Surg. 1973;178:781-786.
29. Dubois A, Kopin IJ, Pettigrew KD, Jacobowitz MD. Chemical and histochemi-
cal studies of postoperative sympathetic activity in the digestive tract of the rat.
Gastroenterology. 1974;66:403-407.
30. De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Herman AG, Pelck-
mans PA. Effect of adrenergic and nitrergic blockade on experimental ileus in
rats. Br J Pharmacol. 1997;120:464-468.
31. Deloof S, Croix D, Tramu G. The role of vasoactive intestinal polypeptide in the
inhibition of antral and pyloric electrical activity in rabbits. J Auton Nerv Syst.
1988;22:167-173.
32. Holzer P, Lippe IT. Inhibition of gastrointestinal transit due to surgical trauma
or peritoneal irritation is reduced in capsaicin-treated rats. Gastroenterology.
1986;91:360-363.
33. Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Her-
man AG. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neu-
rotransmitter. Nature. 1990;345:346-347.
34. Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ. Role of inducible ni-
tric oxide synthase in postoperative intestinal smooth muscle dysfunction in
rodents. Gastroenterology. 2000;118:316-327.
35. DeWinter BY, Robberecht P, Boeckxstaens GE, et al. Role of VIP1/PACAP re-
ceptors in postoperative ileus in rats. Br J Pharmacol. 1998;124:1181-1186.
36. Freeman ME, Guozhang C, Hocking MP. Role of alpha- and beta-calcitonin gene–
related peptide in postoperative small bowel ileus. J Gastrointest Surg. 1999;
3:39-43.
37. De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Herman AG, Pelck-
mans PA. Effects of µ- and ␬-opioid receptors on postoperative ileus in rats.
Eur J Pharmacol. 1997;339:63-67.
38. Kehlet H, Holte K. Review of postoperative ileus. Am J Surg. 2001;182(suppl
5A):3S-10S.
39. Konturek SJ, Thor P, Krol R, Dembinski A, Schally AV. Influence of methionine-
enkephalin and morphine on myoelectric activity of small bowel. Am J Physiol.
1980;238:G384-G389.
40. Terawaki Y, Takayanagi I, Takagi K. Effects of 5-hydroxytryptamine and mor-
phine on the stomach motility in situ. Jpn J Pharmacol. 1976;26:7-12.
41. Turnbull AV, Rivier C. Corticotropin-releasing factor (CRF) and endocrine re-
sponses to stress: CRF receptors, binding protein, and related peptides. Proc
Soc Exp Biol Med. 1997;215:1-10.
42. Taché Y, Martinez V, Million M, Rivier J. Corticotropin-releasing factor and the
brain-gut motor response to stress. Can J Gastroenterol. 1999;13(suppl A):
18A-25A.
43. Taché Y, Monnikes H, Bonaz B, Rivier J. Role of CRF in stress-related alterations
of gastric and colonic motor function. Ann N Y Acad Sci. 1993;697:233-243.
44. Raybould HE, Koelbel CB, Mayer EA, Taché Y. Inhibition of gastric motor func-
tion by circulating corticotropin-releasing factor in anesthetized rats. J Gas-
trointest Motil. 1990;2:265-272.
45. Williams CL, Peterson JM, Villar RG, Burks TF. Corticotropin-releasing factor
directly mediates colonic response to stress. Am J Physiol. 1987;253:G582-
G586.
46. Taché Y, Maeda-Hagiwara M, Turkelson CM. Central nervous system action of
corticotropin-releasing factor to inhibit gastric emptying in rats. Am J Physiol.
1987;253:G241-G245.
47. Sheldon RJ, Qi JA, Porreca F, Fisher LA. Gastrointestinal motor effects of cor-
ticotropin-releasing factor in mice. Regul Pept. 1990;28:137-151.
48. Pappas TN, Welton M, Taché Y, Rivier J. Corticotropin-releasing factor inhibits
gastric emptying in dogs: studies on mechanism of action. Peptides. 1988;8:
1011-1014.
49. Lenz HJ, Burlage M, Raedler A, Greten H. Central nervous system effects of
corticotropin-releasing factor on gastrointestinal transit in the rat. Gastroen-
terology. 1988;94:598-602.
50. Broccardo M, Improta G. Pituitary-adrenal and vagus modulation of sauvagine-
and CRF-induced inhibition of gastric emptying in rats. Eur J Pharmacol. 1990;
182:357-362.
51. Nozu T, Martinez V, Rivier J, Taché Y. Peripheral urocortin delays gastric
emptying: role of CRF receptor 2. Am J Physiol. 1999;276:867-875.
52. Naito Y, Fukata J, Tamai S, et al. Biphasic changes in hypothalamo-pituitary-
adrenal function during the early recovery period of major abdominal surgery.
J Clin Invest. 1991;73:111-117.
53. Donal RA, Perry EG, Wittert GA, et al. The plasma ACTH, AVP, CRH, and cat-
echolamines responses to conventional and laparoscopic cholecystectomy. Clin
Endocrinol (Oxf). 1993;38:609-615.
54. Calogero AE, Norton JA, Sheppard BC, et al. Pulsatile activation of the hypo-
thalamic-pituitary-adrenal axis during major surgery. Metabolism. 1992;41:
839-845.
55. Edwards AV, Jones CT. Secretion of corticotropin-releasing factor from the ad-
(REPRINTED) ARCH SURG/ VOL 138, FEB 2003
213
©2003 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Alabama-Birmingham User on 01/01/2013
renal during splanchnic nerve stimulation in conscious calves. J Physiol. 1988;
400:89-100.
56. Mazzocchi G, Malendowicz LK, Rebuffat P, Tortorella C, Nussdorfer GG. Arginine-
vasopressin stimulates CRH and ACTH release by rat adrenal medulla, acting
via the V1 receptor subtype and a protein kinase C–dependent pathway. Pep-
tides. 1997;18:191-195.
57. Kalff JC, Wolfgang HS, Simmons RL, Bauer AJ. Surgical manipulation of the
gut elicits an intestinal muscularis inflammatory response resulting in post-
surgical ileus. Ann Surg. 1998;228:652-663.
58. Schwarz NT, Kalff JC, Turler A, et al. Prostanoid production via COX-2 as a caus-
ative mechanism of rodent postoperative ileus. Gastroenterology. 2001;121:
1354-1371.
59. Ogilvy AJ, Smith G. The gastrointestinal tract after anesthesia. Eur J Anaesthe-
siol Suppl. 1995;10:35-42.
60. Rashid MU, Bateman DN. Effects of intravenous atropine on gastric emptying,
paracetamol absorption, salivary flow and heart rate in young and elderly vol-
unteers. Br J Clin Pharmacol. 1990;30:25-34.
61. Schurizek BA, Willacy LHO, Kraglund K, Andreasen F, Juhl B. Effects of general
anaesthesia with halothane on antroduodenal motility, pH and gastric empty-
ing in man. Br J Anaesth. 1989;62:129-137.
62. Schurizek BA, Willacy LHO, Kraglund K, Andreasen F, Juhl B. Effects of general
anaesthesia with enflurane on antroduodenal motility, pH and gastric empty-
ing in man. Eur J Anaesthesiol. 1989;6:265-279.
63. Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia: their role in
postoperative outcome. Anesthesiology. 1995;82:1474-1506.
64. Steinbrook RA. Epidural anesthesia and gastrointestinal motility. Anesth An-
alg. 1998;86:837-844.
65. Holte K, Kehlet H. Epidural anesthesia and analgesia-effects on surgical stress re-
sponses and implications for postoperative nutrition. Clin Nutr. 2002;21:199-
206.
66. Wallin G, Cassuto J, Hogstrom S, Rimback G, Faxen B, Tollesson PO. Failure of
epidural anesthesia to prevent postoperative paralytic ileus. Anesthesiology. 1986;
65:292-297.
67. Scheinin B, Asantila R, Orko R. The effect of bupivacaine and morphine on pain
and bowel function after colonic surgery. Acta Anaesthesiol Scand. 1987;31:
161-164.
68. Ahn H, Bronge A, Johansson K, Ygge H, Lindhagen J. Effect of continuous post-
operative epidural analgesia on intestinal motility. Br J Surg. 1988;75:1176-1178.
69. Wattwil M, Thoren T, Hennerdal S, Garvil JE. Epidural analgesia with bupiv-
acaine reduces postoperative paralytic ileus after hysterectomy. Anesth Analg.
1989;68:353-358.
70. Bredtmann RD, Herden HN, Teichmann W, et al. Epidural analgesia in colonic sur-
gery: results of a randomized prospective study. Br J Surg. 1990;77:638-642.
71. Riwar A, Schar B, Grotzinger U. Effect of continuous postoperative analgesia
with peridural bupivacaine on intestinal motility following colorectal resection
[in German]. Helv Chir Acta. 1991;58:729-733.
72. Liu SS, Carpenter RL, Mackey DC, et al. Effects of perioperative analgesic tech-
nique on rate of recovery after colon surgery. Anesthesiology. 1995;83:757-765.
73. Neudecker J, Schwenk W, Junghans T, Pietsch S, Bohm B, Muller JM. Ran-
domized controlled trial to examine the influence of thoracic epidural analgesia
on postoperative ileus after laparoscopic sigmoid resection. Br J Surg. 1999;
98:1292-1295.
74. Asantila R, Eklund P, Rosenberg PH. Continuous epidural infusion of bupiv-
acaine and morphine for postoperative analgesia after hysterectomy. Acta Ana-
esthesiol Scand. 1991;35:513-517.
75. Thoren T, Sundberg A, Wattwil M, Garvill JE, Jurgensen U. Effects of epidural
bupivacaine and epidural morphine on bowel function and pain after hysterec-
tomy. Acta Anaesthesiol Scand. 1989;33:181-185.
76. Jorgensen H, Fomsgaard JS, Dirks J, Wetterslev J, Andreasson B, Dahl JB. Ef-
fect of epidural bupivacaine vs combined epidural bupivacaine and morphine
on gastrointestinal function and pain after major gynaecological surgery. Br
J Anaesth. 2001;87:727-732.
77. Bisgaard C, Mouridsen P, Dahl JB. Continuous lumbar epidural bupivacaine plus
morphine versus epidural morphine after major abdominal surgery. Eur J Ana-
esthesiol. 1990;7:219-225.
78. Hjortso NC, Neumann P, Frosig F, et al. A controlled study on the effect of epi-
dural analgesia with local anaesthetics and morphine on morbidity after ab-
dominal surgery. Acta Anaesthesiol Scand. 1985;29:790-796.
79. Reisine T, Pasternak G. Opioid analgesics and antagonists. In: Hardman JG,
Limbird LE, eds. Goodman & Gilman’s The Pharmacological Basis of Thera-
peutics. 9th ed. New York, NY: McGraw-Hill Co; 1996.
80. Borody TJ, Quigley EM, Phillips SF, et al. Effects of morphine and atropine on
motility and transit in the human ileum. Gastroenterology. 1985;89:562-570.
81. Foss JF. A review of the potential role of methylnaltrexone in opioid bowel dys-
function. Am J Surg. 2001;182(suppl 5A):19S-26S.
WWW.ARCHSURG.COM
 82. Taguchi A, Sharma N, Saleem RM, et al. Selective inhibition of gastrointestinal
opioid receptors. N Engl J Med. 2001;345:935-940.
83. Cheatham ML, Chapman WC, Key SP, Sawyers JL. A meta-analysis of selec-
tive versus routine nasogastric decompression after elective laparotomy. Ann
Surg. 1995;221:469-476.
84. Sagar PM, Kruegener G, MacFie J. Nasogastric intubation and elective abdomi-
nal surgery. Br J Surg. 1992;79:1127-1137.
85. Richter HM, Kelly KA. Effect of transection and pacing on human jejunal pace-
setter potentials. Gastroenterology. 1986;91:1380-1385.
86. Johnson LR. Physiology of the Gastrointestinal Tract. New York, NY: Raven Press;
1994.
87. Stewart BT, Woods RJ, Collopy BT, Fink RJ, Mackay JR, Keck JO. Early feeding
after elective open colorectal resections: a prospective randomized trial. Aust
N Z J Surg. 1998;68:125-128.
88. Di Fronzo LA, Cymerman J, O’Connell TX. Factors affecting early postoperative
feeding following elective open colon resection. Arch Surg. 1999;134:941-945.
89. Macmillan SLM, Kammerer-Doak D, Rogers RG, Parker KM. Early feeding and
the incidence of gastrointestinal symptoms after major gynecologic surgery.
Obstet Gynecol. 2000;96:604-608.
90. Heslin MJ, Latkany L, Leung D, et al. A prospective, randomized trial of early
enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg.
1997;226:567-577.
91. Watter JM, Kirkpatrick SM, Norris SB, Shamji FM, Wells GA. Immediate post-
operative feeding results in impaired respiratory mechanics and decreased mo-
bility. Ann Surg. 1997;226:369-377.
92. Leung KL, Lai PB, Ho RL, et al. Systemic cytokine response after laparoscopic-
assisted resection of rectosigmoid carcinoma: a prospective randomized trial.
Ann Surg. 2000;231:506-511.
93. Lacy AM, Garcia-Valdecasas JC, Pique JM, et al. Short-term outcome analysis
of a randomized study comparing laparoscopic vs open colectomy for colon
cancer. Surg Endosc. 1995;9:1101-1105.
94. Bohm B, Milsom JW, Fazio VW. Postoperative intestinal motility following
conventional and laparoscopic intestinal surgery. Arch Surg. 1995;130:415-
419.
95. Senagore AJ, Luchtefeld MA, Mackeigan JM, Mazier WP. Open colectomy
versus laparoscopic colectomy: are there differences? Am Surg. 1993;59:
549-553.
96. Schwenk W, Bohm B, Haase O, Junghans T, Muller JM. Laparoscopic versus
conventional colorectal resection: a prospective randomised study of postop-
erative ileus and early feeding. Langenbecks Arch Surg. 1998;383:49-55.
97. Merry B, Power W. Perioperative NSAIDs: towards greater safety. Pain Rev. 1995;
2:268-291.
98. Yee MK, Evans WD, Facey PE, Hayward MW, Rosen M. Gastric emptying and
small bowel transit in male volunteers after i.m. ketorolac and morphine. Br
J Anaesth. 1991;67:426-431.
99. Kelley MC, Hocking MP, Marchand SD, Sninsky CA. Ketorolac prevents post-
operative small intestinal ileus in rats. Am J Surg. 1993;165:107-111.
100. De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Herman AG, Pelck-
mans PA. Differential effect of indomethacin and ketorolac on postoperative il-
eus in rats. Eur J Pharmacol. 1998;344:71-76.
101. Cheng G, Cassissi C, Drexler PF, Vogel SB, Sninsky CA, Hocking MP. Salsalate,
morphine, and postoperative ileus. Am J Surg. 1996;171:85-88.
102. Ferraz AA, Cowles VE, Condon RE, et al. Nonopioid analgesics shorten the
duration of postoperative ileus. Am Surg. 1995;61:1079-1083.
103. Fanning J, Yu-Brekke S. Prospective trial of aggressive postoperative bowel
stimulation following radical hysterectomy. Gynecol Oncol. 1999;73:412-414.
104. Ruwart MJ, Klepper MS, Rush BD. Mechanism of stimulation of gastrointes-
tinal propulsion in postoperative ileus rats of 16, 16-dimethyl PGE2. Adv
Prostaglandin Thromboxane Res. 1980;8:1603-1607.
105. Heimbach DM, Crout JR. Treatment of paralytic ileus with adrenergic neuronal
blocking drugs. Surgery. 1971;69:582-587.
106. Furness JB, Costa M. Adynamic ileus, its pathogenesis and treatment. Med Biol.
1974;52:82-89.
107. Kleinfeld D. Edrophonium used for vagotonic action. JAMA. 1973;223:922-923.
108. Burks TF. Neurotransmission and neurotransmitters. In: Johnson LR, Alpers
DM, Christensen J, Jacobson ED, Walsh JH, eds. Physiology of the Gastrointes-
tinal Tract. Vol 1. 3rd ed. New York, NY: Raven Press; 1994.
109. Kreis ME, Kasparek M, Zittel TT, Becker HD, Jehle EC. Neostigmine increases
postoperative colonic motility in patients undergoing colorectal surgery. Sur-
gery. 2001;130:449-456.
110. Jepsen S, Klaerke A, Nielsen PH, Simonsen O. Negative effect of metoclopra-
(REPRINTED) ARCH SURG/ VOL 138, FEB 2003
214
©2003 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Alabama-Birmingham User on 01/01/2013
mide in postoperative adynamic ileus: a prospective, randomized, double blind
study. Br J Surg. 1986;73:290-291.
111. Cheape JD, Wexner SD, James K, Jagelman DG. Does metoclopramide reduce
the length of ileus after colorectal surgery? a prospective randomized trial. Dis
Colon Rectum. 1991;34:437-441.
112. Tollesson PO, Cassuto J, Faxen A, Rimback G, Mattsson E, Rosen S. Lack of
effect of metoclopramide on colonic motility after cholecystectomy. Eur J Surg.
1991;157:355-358.
113. Breivik H, Lind B. Anti-emetic and propulsive peristaltic properties of metoclo-
pramide. Br J Anaesth. 1971;43:400-403.
114. Davidson ED, Hersh T, Brinner RA, Barnett SM, Boyle LP. The effects of met-
oclopramide on postoperative ileus: a randomized double blind study. Ann Surg.
1979;190:27-30.
115. Kivalo I, Miettinen K. The effects of metoclopramide on postoperative nausea
and bowel function. Ann Chir Gynaecol Fenn. 1970;59:155-158.
116. Seta ML, Kale-Pradham PB. Efficacy of metoclopramide in postoperative ileus
after exploratory laparotomy. Pharmacotherapy. 2001;10:1181-1186.
117. Smith AJ, Nissan A, Lanouette NM, et al. Prokinetic effect of erythromycin af-
ter colorectal surgery: randomized, placebo-controlled, double-blind study. Dis
Colon Rectum. 2000;43:333-337.
118. Bonacini M, Quiason S, Reynolds M, Gaddis M, Pemberton B, Smith O. Effect of
erythromycin on postoperative ileus. Am J Gastroenterol. 1993;88:208-211.
119. Tollesson PO, Cassuto J, Rimback G, Faxen A, Bergman L, Mattsson E. Treat-
ment of postoperative paralytic ileus with cisapride. Scand J Gastroenterol. 1991;
26:477-482.
120. Brown TA, McDonald J, Williard W. A prospective, randomized, double-
blinded, placebo-controlled trial of cisapride after colorectal surgery. Am J Surg.
1999;177:399-401.
121. Boghaert B, Haesaert G, Mourisse P, Verlinden M. Placebo-controlled trial of
cisapride in postoperative ileus. Acta Anaesthesiol Belg. 1987;38:195-199.
122. Verlinden M, Michiels G, Boghaert A, de Coster M, Dehertog P. Treatment of
postoperative gastrointestinal atony. Br J Surg. 1987;74:614-617.
123. von Ritter C, Hunter S, Hinder RA. Cisapride does not reduce postoperative il-
eus. S Afr J Surg. 1987;25:19-21.
124. Lander B, Redkar R, Nicholls G, et al. Cisapride reduces neonatal postoperative
ileus: randomised placebo controlled trial. Arch Dis Child Fetal Neonatal Ed. 1997;
77:F119-F122.
125. Barone JA, Jessen LM, Colaizzi JL, Bierman RH. Cisapride: a gastrointestinal
prokinetic drug. Ann Pharmacother. 1994;28:488-500.
126. Hallerback H, Bergman B, Bong H, et al. Cisapride in the treatment of post-
operative ileus. Aliment Pharmacol Ther. 1991;5:503-511.
127. Roberts JP, Benson MJ, Rodgers J, Deeks JJ, Wingate DL, Williams NS. Effect
of cisapride on distal colonic motility in the early postoperative period follow-
ing left colonic anastomosis. Dis Colon Rectum. 1995;38:139-145.
128. Sadek SA, Cranford C, Eriksen C, et al. Pharmacological manipulation of ady-
namic ileus: controlled randomized double-blind study of ceruletide on intes-
tinal motor activity after elective abdominal surgery. Aliment Pharmacol Ther.
1988;2:47-54.
129. Madsen PV, Lykkegaard-Nielsen M, Nielsen OV. Ceruletide reduces postopera-
tive intestinal paralysis: a double-blind placebo-controlled trial. Dis Colon Rec-
tum. 1983;26:159-160.
130. Cullen JJ, Eagon JC, Kelly KA. Gastrointestinal peptide hormones during post-
operative ileus: effect of octreotide. Dig Dis Sci. 1994;39:1179-1184.
131. Asao T, Kuwano H, Nakamura J, Moringa N, Hirayama I, Ide M. Gum chewing
enhances early recovery from postoperative ileus after laparoscopic colec-
tomy. J Am Coll Surg. 2002;195:30-32.
132. Soffer EE, Adrian TE. Effect of meal composition and sham feeding on duode-
nojejunal motility in humans. Dig Dis Sci. 1992;37:1009-1014.
133. Katschinski M, Dahmen G, Reinshagen M, et al. Cephalic stimulation of GI secre-
tory and motor response in humans. Gastroenterology. 1992;103:383-391.
134. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of
salt and water balance on gastrointestinal function after elective colon resec-
tion. Lancet. 2002;359:1812-1818.
135. Basse L, Madsen JL, Kehlet H. Normal gastrointestinal transit after colonic re-
section using epidural analgesia, enforced oral nutrition and laxative. Br J Surg.
2001;88:1498-1500.
136. Waldenhausen JH, Schirmer BD. The effect of ambulation on recovery from post-
operative ileus. Ann Surg. 1990;212:671-677.
137. Basse L, Jacobsen D, Billesbolle P, et al. A clinical pathway to accelerate re-
covery after colonic resection. Ann Surg. 2000;232:51-57.
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