1. science
2. medicine
3. surgery

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. Gastroenterology 1988 June;94(6):1351-6.
4. Behm B, Stollman N. Postoperative ileus: etiologies and interventions. Clin Gastroenterol
Hepatol 2003 March;1(2):71-80.
28. Manara L, Bianchetti A. The central and peripheral influences of opioids on gastrointestinal propulsion. Annu Rev Pharmacol Toxicol 1985;25:249-73.
5. Luckey A, Livingston E, Tache Y. Mechanisms and treatment of postoperative ileus. Arch
Surg 2003 February;138(2):206-14.
29. Manara L, Bianchi G, Ferretti P, Tavani A. Inhibition of gastrointestinal transit by morphine
in rats results primarily from direct drug action on gut opioid sites. J Pharmacol Exp Ther
1986 June;237(3):945-9.
6. Livingston EH, Passaro EP, Jr. Postoperative ileus. Dig Dis Sci 1990 January;35(1):121-32.
30. Brix-Christensen V, Tonnesen E, Sanchez RG, Bilfinger TV, Stefano GB. Endogenous
morphine levels increase following cardiac surgery as part of the antiinflammatory
response? Int J Cardiol 1997 December 19;62(3):191-7.
7. Waldhausen JH, Shaffrey ME, Skenderis BS, Jones RS, Schirmer BD. Gastrointestinal
myoelectric and clinical patterns of recovery after laparotomy. Ann Surg 1990
June;211(6):777-84.
31. Brix-Christensen V, Goumon Y, Tonnesen E, Chew M, Bilfinger T, Stefano GB. Endogenous
morphine is produced in response to cardiopulmonary bypass in neonatal pigs. Acta
Anaesthesiol Scand 2000 November;44(10):1204-8.
8. Wilson JP. Postoperative motility of the large intestine in man. Gut 1975
September;16(9):689-92.
9. Woods JH, Erickson LW, Condon RE, Schulte WJ, Sillin LF. Postoperative ileus: a colonic
problem? Surgery 1978 October;84(4):527-33.
32. Yoshida S, Ohta J, Yamasaki K et al. Effect of surgical stress on endogenous morphine and
cytokine levels in the plasma after laparoscopoic or open cholecystectomy. Surg Endosc
2000 February;14(2):137-40.
10. Delaney CP, Senagore AJ, Viscusi ER et al. Postoperative upper and lower gastrointestinal
recovery and gastrointestinal morbidity in patients undergoing bowel resection: pooled
analysis of placebo data from 3 randomized controlled trials. Am J Surg 2006
March;191(3):315-9.
33. Kehlet H. Endogenous morphine--another component and biological modifier of the
response to surgical injury? Acta Anaesthesiol Scand 2000 November;44(10):1167-8.
34. Yuan CS, Foss JF. Antagonism of gastrointestinal opioid effects. Reg Anesth Pain Med 2000
November;25(6):639-42.
11. Holte K, Kehlet H. Postoperative ileus: progress towards effective management. Drugs
2002;62(18):2603-15.
35. Ferraz AA, Cowles VE, Condon RE et al. Nonopioid analgesics shorten the duration of postoperative ileus. Am Surg 1995 December;61(12):1079-83.
12. Clevers GJ, Smout AJ, van der Schee EJ, Akkermans LM. Myo-electrical and motor
activity of the stomach in the first days after abdominal surgery: evaluation by electrogastrography and impedance gastrography. J Gastroenterol Hepatol 1991 May;6(3):253-9.
36. Delaney CP. Clinical perspective on postoperative ileus and the effect of opiates.
Neurogastroenterol Motil 2004 October;16 Suppl 2:61-6.
13. Szurszewski JH. A migrating electric complex of canine small intestine. Am J Physiol 1969
December;217(6):1757-63.
37. Yuan CS, Israel RJ. Methylnaltrexone, a novel peripheral opioid receptor antagonist for the
treatment of opioid side effects. Expert Opin Investig Drugs 2006 May;15(5):541-52.
14. Kehlet H, Holte K. Review of postoperative ileus. Am J Surg 2001 November;182(5A
Suppl):3S-10S.
38. Yuan CS. Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction
and other opioid adverse effects. Ann Pharmacother 2007 June;41(6):984-93.
15. Jorgensen H, Wetterslev J, Moiniche S, Dahl JB. Epidural local anaesthetics versus
opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and
pain after abdominal surgery. Cochrane Database Syst Rev 2000;(4):CD001893.
38. Delaney CP, Wolff BG, Viscusi ER et al. Alvimopan, for postoperative ileus following bowel
resection: a pooled analysis of phase III studies. Ann Surg 2007 March;245(3):355-63.
40. Lowman RM. The potassium depletion states and postoperative ileus. The role of the
potassium ion. Radiology 1971 March;98(3):691-4.
16. Kalff JC, Schraut WH, Simmons RL, Bauer AJ. Surgical manipulation of the gut elicits an
intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg 1998
November;228(5):652-63.
41. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg
2002 June;183(6):630-41.
17. Schwarz NT, Beer-Stolz D, Simmons RL, Bauer AJ. Pathogenesis of paralytic ileus: intestinal manipulation opens a transient pathway between the intestinal lumen and the leukocytic infiltrate of the jejunal muscularis. Ann Surg 2002 January;235(1):31-40.
42. Waldhausen JH, Schirmer BD. The effect of ambulation on recovery from postoperative
ileus. Ann Surg 1990 December;212(6):671-7.
18. Schwarz NT, Kalff JC, Turler A et al. Prostanoid production via COX-2 as a causative
mechanism of rodent postoperative ileus. Gastroenterology 2001 December;121(6):
1354-71.
43. Kehlet H. Surgical stress response: does endoscopic surgery confer an advantage? World
J Surg 1999 August;23(8):801-7.
44. 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 October;9(10):1101-5.
19. Kalff JC, Buchholz BM, Eskandari MK et al. Biphasic response to gut manipulation and
temporal correlation of cellular infiltrates and muscle dysfunction in rat. Surgery 1999
September;126(3):498-509.
45. Schwenk W, Bohm B, Haase O, Junghans T, Muller JM. Laparoscopic versus conventional
colorectal resection: a prospective randomised study of postoperative ileus and early
postoperative feeding. Langenbecks Arch Surg 1998 March;383(1):49-55.
20. Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ. Role of inducible nitric oxide
synthase in postoperative intestinal smooth muscle dysfunction in rodents.
Gastroenterology 2000 February;118(2):316-27.
46. Milsom JW, Bohm B, Hammerhofer KA, Fazio V, Steiger E, Elson P. A prospective,
randomized trial comparing laparoscopic versus conventional techniques in colorectal
cancer surgery: a preliminary report. J Am Coll Surg 1998 July;187(1):46-54.
21. de Jonge WJ, van den Wijngaard RM, The FO et al. Postoperative ileus is maintained by
intestinal immune infiltrates that activate inhibitory neural pathways in mice.
Gastroenterology 2003 October;125(4):1137-47.
22. Holte K, Sharrock NE, Kehlet H. Pathophysiology and clinical implications of perioperative
fluid excess. Br J Anaesth 2002 October;89(4):622-32.
47. 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
April;231(4):506-11.
23. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and
water balance on recovery of gastrointestinal function after elective colonic resection: a
randomised controlled trial. Lancet 2002 May 25;359(9320):1812-8.
48. Abraham NS, Byrne CM, Young JM, Solomon MJ. Meta-analysis of non-randomized
comparative studies of the short-term outcomes of laparoscopic resection for colorectal
cancer. ANZ J Surg 2007 July;77(7):508-16.
24. Bauer AJ, Sarr MG, Szurszewski JH. Opioids inhibit neuromuscular transmission in
circular muscle of human and baboon jejunum. Gastroenterology 1991 October;101(4):
970-6.
49. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction.
Am J Surg 2001 November;182(5A Suppl):11S-8S.
8