S

ince the mid-1970s, remarkable

advances have been made in
anesthesiology, perioperative care, and
surgical techniques that allow surgeons to
perform more extensive and radical procedures
using a patient-friendly approach. According to
data from the Healthcare Cost and Utilization
Project (HCUP) Nationwide Inpatient Sample
(NIS), more than 500,000 elective major
abdominal operations were performed in the
United States in 2006 (Table 1).
1
The total cost
of these procedures exceeded $10 billion.
Although new achievements have dramati-
cally improved the quality of care and the spec-
trum of surgical options, many old problems,
such as infection, hemorrhage, and postopera-
tive ileus (POI) still persist and pose challenges
to the medical community.
2-5
Accordingly, as
minimally invasive techniques and minimal
access surgery have continued to improve, sur-
geons and other specialists have sharpened their
focus on these persistent obstacles to improved
patient outcomes.
6
POI, or paralytic ileus, is defined as a tran-
sient, functional impairment of intestinal motil-
ity occurring after surgery.
7
The most common
factors associated with the development of ileus
include several types of surgery (gynecologic,
urologic, thoracic, orthopedic, general surgi-
cal, or colorectal surgical procedures). Abdom-
inal surgery, postoperative opioid analgesics,
prolonged sedentary recovery, and the use of
inhalant anesthetics all have been reported as
contributing to POI. Ileus is generally considered
virtually normal or inevitable after most major
surgical procedures. Laparotomy, which includes
colorectal surgery, is one of the most frequent
causes of POI; up to 40% of patients undergoing
laparotomy experience POI.
8,9
Reconstructive
BADMA BASHANKAEV, MD
Clinical Research Fellow
Department of Colorectal Surgery
Cleveland Clinic Florida
Weston, Florida
MARAT KHAIKIN, MD
Department of Surgery and
Transplantation
Sheba Medical Center
Sackler School of Medicine
Tel-Aviv, Israel
STEVEN D. WEXNER, MD
Chief Academic Officer
Professor and Chairman
Department of Colorectal Surgery
Cleveland Clinic Florida
Weston, Florida
MARSHA DANIEL, PHARMD, CPH
Department of Pharmacy
Cleveland Clinic Florida
Weston, Florida
Postoperative
Ileus:
An Algorithm for Prevention
and Management
PRINTER-FRIENDLY VERSION AT PHARMACYPRACTICENEWS.COM
71
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG PHARMACY PRACTI CE NEWS SPECI AL EDI TI ON 2009
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
radical cystectomy also is associ-
ated with a high (up to 17%) rate
of ileus.
10
Even surgery of the hip
or knee can lead to ileus, with as
many as 4% of patients devel-
oping intestinal motility impair-
ments after total hip or knee
arthroplasty.
11
Stany and Farley, in
their review of complications in
gynecologic surgery, noted that
approximately 3% of patients
who undergo total abdominal
hysterectomy also develop POI.
12
Normal bowel function requires
coordination of motility, mucosal
transport, and evacuatory reflexes
in the gastrointestinal (GI) tract.
GI motility must be considered
an integrated process of elec-
trophysiologic activitywhich
includes smooth muscle function
with neural input from the intrin-
sic and autonomic nervous sys-
temsaccompanied by hormonal
interactions. Thus, the pathogen-
esis of POI is multifactorial and
includes activation of inhibitory
reflexes, inflammatory mediators,
and endogenous and exogenous
opioids.
13
Physical, Psychological, and
Economic Impacts of POI
Physiologic awakening of GI
tract function after abdominal
surgery is generally thought to
occur in sequence: first, in the
small intestine and the stomach,
and, ultimately, in the colon. Failure of the postopera-
tive patient to tolerate a diet, have flatus, and experi-
ence a bowel movement within 5 days after laparotomy
or within 3 days after laparoscopic surgery, are indic-
ative of a prolonged POI.
14,15
Clinical presentation of
POI is accompanied by abdominal distention, delayed
or absent passage of gas, delayed or absent passage
of stool, decreased, or the absence of, bowel sounds,
and accumulation of gas and fluid in the bowel with
attendant nausea and/or vomiting.
16,17
Nausea caused
by ileus usually is described by patients as a very taxing
postoperative complication. Another important clinical
manifestation of POI is recurrence of ileus, which can
happen even after the patient is discharged from the
hospital. Readmission occurs in approximately 10% of
post-abdominal surgery patients, approximately half of
whom are readmitted for GI failure or some measure of
recurrent, or perhaps incompletely resolved, POI.
14
POI
makes physical recovery more difficult, has a detrimen-
tal psychological effect on patients, and increases the
potential for wound infection, pulmonary complications,
and postoperative malnutrition.
18-23
In turn, the physi-
cal and psychological side effects of POI lead to pro-
longed hospital length of stay (LOS) and increased
health care costs.
24
In 1999, Prasad, using calculations
published by Moss et al in 1986, estimated that the eco-
nomic impact of ileus and its complications on the US
health care system would exceed $1 billion in 2000.
16,25

In 2000, Woods hypothesized that effective manage-
ment of POIestimating that 750,000 patients could
be discharged an average of 1 day earlier if effectively
managedcould result in a potential savings of $1.1 bil-
lion per year.
26
More recent data from Goldstein et al
suggest that annual costs attributed to managing POI
is approximately $1.5 billion.
27
Coding for POI
There are numerous problems in defining ileus. Unlike
the vast majority of diseases, there are no objective crite-
ria by which ileus can be judged. There are no serologic,
concrete radiographic, or histopathologic examina-
tions that can conclusively diagnose POI and none that
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
72
Table 1. Healthcare Cost and Utilization Project
Nationwide Inpatient Sample (NIS) 2006
Diagnosis-Related Groups
Patients
(n)
Hospital
Length of Stay,
days (mean)
Costs, $
(mean)
146: Rectal resection with CC 21,219 8.9 17,931
147: Rectal resection without CC 8,679 5.2 11,003
148: Major small and large bowel
procedures with CC
211,083 11.1 22,614
149: Major small and large bowel
procedures without CC
71,429 5.2 10,748
150: Peritoneal adhesiolysis with CC 56,072 9.2 17,745
151: Peritoneal adhesiolysis without CC 27,673 4.3 9,128
154: Stomach, esophageal, and duo-
denal procedures, age >17, with CC
42,431 12.2 27,146
155: Stomach, esophageal, and duo-
denal procedures, age >17, without CC
22,477 3.5 9,719
303: Kidney, ureter, and major
bladder procedures for neoplasm
53,779 6.2 14,947
304: Kidney, ureter, and major bladder
procedures for non-neoplasia with CC
38,747 6.7 14,938
305: Kidney, ureter, and major
bladder procedures for
non-neoplasia without CC
26,964 2.7 9,225
353: Pelvic evisceration, radical
hysterectomy, and radical vulvectomy
11,362 5.0 11,753
Total 591,915
CC, complications and comorbidities
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
can grade its severity or predict and risk stratify ileus.
Because it is so elusive, it is even more difficult to mea-
sure any impact that therapy may have upon preven-
tion or prompting the resolution of POI. Specifically, and
again using the analogy of most other diseases, we can
stratify patients by risk to allow prognostication, and,
therefore, optimally assign therapeutic terms. We can
then measure the impact of interventions using objec-
tive pre- and post-therapeutic scales. POI has no such
definable criteria and, therefore, assessing the impact of
any intervention on ileus is exceptionally difficult.
No specific code exists for POI within the various
coding systems (Diagnosis-Related Group, Clinical Clas-
sifications Software codes, and Major Diagnostic Cate-
gories MDC). The closest that one can come to labeling
patients as having ileus is with the use of a combina-
tion of codes from the International Classification of
Diseases, Ninth Revision, Clinical Modification (ICD-
9-CM):
Code 997.4: Digestive system complications: Com-
plications of intestinal (internal anastomosis and
bypass not elsewhere classified, except that involv-
ing the urinary tract);
Code 560.1: Adynamic ileus; ileus (of intestine) (of
bowel) (of colon); paralysis of intestine or colon;
Code 564.4: Other postoperative functional disor-
ders (diarrhea following gastrointestinal surgery).
Regimens for Minimizing and Reducing POI
Attempts have been made to describe a uni-
fied clinical scenario after major abdominal surgery
by deriving pooled data from a homogenous pla-
cebo group of 3 randomized controlled trials (RCTs)
designed to represent typical postoperative recov-
ery after major abdominal colorectal surgery.
28
The
authors reviewed incidences of nausea, vomiting,
nasogastric tube (NGT) insertion, upper and lower
GI recovery, and hospital discharge, as well as read-
mission, in patients who underwent bowel resection
by laparotomy with multimodal postoperative care
designed to minimize POI. This regimen included
early postoperative removal of the orogastric tube or
NGT and the commencement of oral diet immediately
after surgery with increased ambulation and diet on
postoperative day 1 and an offer of solid food on post-
operative day 2. The time to recovery of upper and
lower GI functions were measured by either toleration
of solid food or first bowel movement. Most of the
patients in these studies managed to achieve at least
one of these 2 criteria by postoperative day 4. How-
ever, 30% of patients still had not achieved GI recov-
ery by day 6. Moreover, POI was a serious adverse
event (AE) reported in 9.2% of patients. The major-
ity of patients were discharged from the hospital by
day 6; mean time until the hospital discharge order
written was 6.1 days. However, 25% of patients were
discharged from the hospital on or after postopera-
tive day 7, and 12.2% of patients required insertion of
postoperative NGT during their hospital stay.
Prophylaxis of POI is certainly preferred to therapy.
Every step of the preoperative, operative, and postop-
erative period should be directed toward decreasing
the risk for developing POI. Kehlet summarized that
the underlying rationale for multimodal rehabilitation
is the simultaneous application of several interven-
tions to improve overall postoperative morbidity.
29
The process should commence with preoperative
counseling. Counseling should include a thorough
discussion with the patient and the patients family,
if possible, about the importance of compliance with
the postoperative regimen. Early ambulation and diet
as tolerated should be emphasized.
The surgeon may have the opportunity to perform
the procedure in a laparoscopic manner, in which case
POI may be less severe than after laparotomy. Surgi-
cal manipulation should be based on meticulous tis-
sue handling, with minimal or no tissue trauma, and
meticulous hemostasis. The following grades of evi-
dence have been established for tissue handling:
Gentle handling and minimal manipulation of the
intestines (grade 1C);
Mid-thoracic epidurals with local anesthetics for
postoperative pain control (grade 2A);
Minimally invasive surgery instead of laparotomy
(grade 2C);
Limiting the length of laparotomy incisions (grade
2C); and
Nonsteroidal anti-inflammatory drugs (NSAIDs)
instead of opioids for analgesia (grade 2C).
30
Fast-Track Protocols
Implementation of an enhanced recovery strategy for
after surgery, or a fast-track protocol, has significantly
reduced the incidence of POI.
31-34
The protocol is a set
of perioperative measures that includes both preoper-
ative counseling (including the distribution and review
of printed educational materials) and postoperative care
pathways. The protocol calls for the absence of mechan-
ical bowel preparation, standard general anesthesia
without premedication, limited intraoperative fluid resus-
citation, high concentrations of perioperative oxygen, use
of epidural analgesia, standardized general anesthesia,
minimal or transverse incisions, abandonment of routine
use of NGTs, limited use of drains, enforced early postop-
erative mobilization, and opioid-sparing analgesia. Other
measures include early nutrition and early bladder cath-
eter removal.
35,36
Every step of the fast-track protocol is
evidence-based and oriented toward reducing surgery-
related physical and psychological stressors.
37

The Effects of Opioids and Fluid Management
Opioid drugs, the historical drugs of choice for post-
operative analgesia, are known to have negative effects
on various parts of GI system through presynaptic block-
age of excitatory neurons, specific membrane recep-
tors, and activation of 2-receptors, leading to bowel
dysfunction. Some known effects of opioids on the GI
tract are listed in Table 2.
38
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
73
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
The use of postoperative opioid analgesics clearly
exacerbates ileus. Accordingly, both IV patient-con-
trolled analgesia and epidural opioid administration
have been routinely used in an attempt to reduce dys-
motility and POI inception and exacerbation.
7
More
recently, the use of NSAIDs, such as ketorolac and ibu-
profen, has been recommended to reduce the use of
opioids. Administration of NSAIDs in the early post-
operative period not only produces opioid-steering
effects, but it also directly affects prostaglandin syn-
thesis and decreases inflammation. Wider application
of thoracic epidural administration of local anesthet-
ics combined with IV lidocaine has been reported to
effectively mitigate the postoperative effects of colon
surgery by reducing cytokine levels and pain, and facil-
itating bowel function.
39
The management of excessive fluid during the early
postoperative phase leads to sequestration of fluid in
the intestinal wall, which can further hamper GI motility
and thereby prolong POI and its numerous adverse
sequelae.
40
A meta-analysis performed by the Heidel-
berg group showed the benefits of restrictive rather
than standard fluid replacement after colorectal resec-
tion by reducing postoperative morbidity.
37
Laparoscopy and POI
Laparoscopy has been shown to significantly
decrease tissue trauma and postoperative pain, thereby
decreasing both the local inflammatory component of
ileus as well as the need for opioids with the attendant
AEs of the opioids. Added benefits of the laparoscopic
approach include improved pulmonary function, which
lowers the risk for developing pneumonia, atelectasis,
and other problems that predispose a patient to fur-
ther bed rest.
17
A Cochrane review of short-term bene-
fits for laparoscopic colorectal resection that included
8 studies of 1,116 patients showed that flatus was
achieved 1 day earlier with laparoscopy than with lap-
arotomy (P<0.0001). Also, data collected from 9 tri-
als that included 1,130 patients showed that patients
who underwent laparoscopy reported their first bowel
movement 0.9 days earlier than patients in the laparo-
tomy group (P<0.0001).
41
Traditionally, rectal surgery has been associated with
a more prolonged ileus than colon surgery; however,
with the adaptation of laparoscopic techniques along
with the standard fast-track protocol, hospital LOS has
been decreased to a mean of 3 days, with 90% of the
patients discharged at or before postoperative day 5.
42

The authors also reported a very respectable readmis-
sion rate of 8%, and noted that such impressive results
would not have been possible without an educated and
dedicated team working with patients from the time of
scheduling the surgery to the time of discharge.
With the combination of minimally invasive tech-
niques and these clinical pathways, the instance of POI
and small bowel obstruction after gynecologic opera-
tive laparoscopy was reduced to 0.036%.
12
Nonpharmacologic Modalities for POI
Multiple nonpharmacologic modalities such as acu-
puncture, electrical stimulation, mechanical massage,
and psychological suggestion have been purported
to help prevent or treat POI.
17
Chinese medicine has
a 6,000-year history that includes various modalities
used for surgery. Although some authors speculate
about the potential role of acupuncture and herbal ene-
mas in the treatment of POI, very few data exist in Eng-
lish-language literature.
43
All of these modalities require
further investigation.
One of the most recent trends in ileus treatment
is sham feeding, in which patients are given chewing
gum after surgery. The mechanism of action for reduc-
ing POI is unknown, although authors often cite the
cephalic-vagal stimulation of digestion, bowel motil-
ity, hormonal secretion, and mechanical stimulation of
the motility of the duodenum, stomach, and rectum,
through the secretion of saliva, and pancreatic juices.
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
74
Table 2. Effects of Opioids
On the Gastrointestinal Tract
Gallbladder
Contraction with biliary pain
Spasm in sphincter of Oddi, with delayed
digestion and decreased secretion
Gastroduodenum
Inhibition of gastric emptying causing anorexia
Increased duodenal motility, followed by
quiescence with resulting nausea and emesis
Increased pyloric tone
Enhanced gastric acid secretion
Small bowel
Increased tone/segmentation with constipation
Increased transit time, resulting in delayed
digestion
Increased absorption, causing hard, dry stool
Decreased secretion
Colon
Increased tone/segmentation with constipation
Increased transit time, causing hard, dry stools
Increased absorption, inducing bloating and
distension
Decreased secretion, producing spasm, cramps,
and pain
Anorectum
Decreased rectal sensitivity with feeling of
incomplete evacuation
Increased internal sphincter tone, causing
straining and constipation
Based on reference 38.
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
Sorbitol and other hexitols, the main ingredients in
sugar-free chewing gums, are offered as hypothetical
ileus ameliorating agents.
44
Although a single prospec-
tive, randomized placebo-controlled trial questioned
the effectiveness of chewing gum in postcolectomy
ileus,
45
several meta-analyses have shown that chew-
ing gum does enhance bowel recovery without short-
ening of hospital stay.
46-51
Pharmacologic Management of POI
To date there is no gold standard for the use of phar-
macologic agents for treatment or prevention of ileus,
although there are numerous reports of a variety of
attempts.
17
The Cochrane systematic review of 39 RCTs regard-
ing systemic prokinetic pharmacologic treatment for
POI after abdominal surgery in adults was published in
2008.
52
The review included 4,615 patients who under-
went major abdominal surgery, or major abdominal-vas-
cular surgery, major abdominal urologic or gynecologic
surgery. The review evaluated a variety of agents for
anti-ileus activity, including the following:
cholinergic agonists (bethanechol, neostigmine)
benzamides (cisapride, metoclopramide,
bromopride)
dopamine antagonists (domperidone)
peptide hormones (cholecystokinin, ceruletide,
vasopressin)
adrenergic antagonists (propranolol)
macrolide antibiotic (erythromycin)
ergotamine derivates (dihydroergotamine)
systemic application of local anesthetics
prostaglandins
vitamins (pantothenic acid, dexpanthenol)
selective GI opioid antagonists
ALVIMOPAN
Six RCTs from the Cochrane review support the effec-
tiveness of alvimopan (Entereg, Adolor/GlaxoSmith-
Kline), a novel peripheral -opioid receptor antagonist,
for POI.
52

METHYLNALTREXONE
Methylnaltrexone (Relistor, Progenics Pharmaceuti-
cals, Inc. and Wyeth Pharmaceuticals) is also a periph-
erally acting -opioid antagonist. Although it is a
quaternary derivative of the opioid antagonist naltrex-
one, it is unable to cross the bloodbrain barrier, thus
it maintains the centrally mediated analgesic effects
of opioids. Methylnaltrexone is approved by the FDA
in the subcutaneous injection form for the treatment
of opioid-induced bowel dysfunction (constipation)
in palliative care due to an advanced illness such as
incurable cancer, end-stage heart and lung disease,
and AIDS, as well as in methadone users and patients
suffering from chronic pain.
53,54
As of September 2009,
its application in surgical patients in the United States
was still under investigation.
ERYTHROMYCIN
Erythromycin has shown homogenous and consis-
tent absence of efficacy in numerous trials.
52
Recent
results obtained from a randomized, double-blind,
placebo-controlled study from the University of Iowa
Carver College of Medicine showed no significant differ-
ence between erythromycin IV infusion and placebo.
55

Data from 11 patients in each group who underwent cys-
tectomy with urinary diversion secondary to primary
bladder cancer or interstitial cystitis found that eryth-
romycin was not useful in improving POI as measured
by the time to onset of bowel sounds, passage of fla-
tus, passage of the first bowel movement, or toleration
of a regular diet.
CHOLECYSTOKININ-LIKE AGENTS
The evidence in a Cochrane review was insufficient
to recommend the use of cholecystokinin-like drugs,
cisapride, dopamine antagonists, propranolol, or vaso-
pressin. The effects of these medications were incon-
sistent across outcomes, the trials were quite small, and
the methodology of the trials was sometimes subop-
timal.
52
Moreover, cisapride was withdrawn from the
market in many countries in 2000 because of serious
cardiac toxicity.
However, the concept of preventing sympathetic
inhibition by the prevention of the release of acetylcho-
line from excitatory fibers and myenteric plexus is very
promising. In a recent study from Japan, mosapride, a
serotonin 5-hydroxytryptan-4 receptor agonist with-
out the effect on the dopamine D2 receptor or other
receptors, was administered to patients who underwent
hand-assisted laparoscopic colectomy.
56
Patients in the
mosapride group had a bowel movement 20.8 hours
earlier (P=0.02) and a hospital LOS of 1.7 fewer days
(P=0.04) compared with patients in the control group.
The authors concluded that treatment with mosapride
significantly improves postoperative GI motility and
shortens POI in patients having a laparoscopic colec-
tomy, with no AEs.
LOCAL ANESTHETICS
A Cochrane review has shown that systemic appli-
cation of local anesthetics, such as IV lidocaine and
neostigmine, might have a potential effect on POI,
but more evidence on clinically relevant outcomes is
needed. A research group from Lige, Belgium ran-
domly assigned 40 laparoscopic colectomy patients
into 2 groupsone group received perioperative 2%
lidocaine as a bolus injection of 1.5 mg/kg lidocaine
at the induction of anesthesia, followed by contin-
uous infusion of 2 mg/kg per hour during surgery
and 1.3 mg/kg per hour for the first 24 hours after
surgery. The control group received placebo saline
in coded 50-mL syringes.
57
All patients in the study
were enrolled in an acute rehabilitation program. The
patients who received lidocaine showed statistically
significant reduction in time to passage of first flatus
compared with control group patients (17 vs 28 hours,
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
75
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
respectively; P<0.001), time to first bowel movement
(28 vs 51 hours, respectively; P=0.001), and had a
shorter hospital LOS (2 vs 3 days; P=0.001). Patients
who received lidocaine also required significantly less
analgesia with opioids (8 vs 22 mg; P=0.005), had
less postoperative pain, and experienced less fatigue,
without any differences in either endocrine or meta-
bolic profiles. The authors suggested that IV lidocaine
infusion had an inhibitory effect of N-methyl-D-aspar-
tate receptors, which play a major role in postoper-
ative hyperalgesia and polymorphonuclear leukocyte
priming. A meta-analysis on the effects of lidocaine
on POI was recently published in the British Journal of
Surgery.
58
The meta-analysis, which included 8 RCTs
and 320 patients, concluded that the continuous IV
administration of lidocaine during and after abdomi-
nal surgery improves patient rehabilitation and short-
ens hospital LOS.
Cleveland Clinic Florida Practice
Our practice at Cleveland Clinic Florida includes a
fast-track protocol (Table 3), a component of which is
diet acceleration (Table 4). We do not employ epidu-
ral analgesia, but we do use patient-controlled analge-
sia. Patients are expected to ambulate commencing the
day of surgery and attempt to ingest clear fluids on the
day of surgery. The absence of progress at any step, or
the development of nausea and/or vomiting, may lead
to the acceleration of the protocol.
Ultimately, the biggest challenge in treating POI may
be distinguishing it from other postoperative intra-
abdominal problems, including an anastomotic leak,
sepsis, fluid collection, electrolyte imbalance, pneumo-
nia, or bowel obstruction.
15
When any collection exists
within the bowel, a water-soluble upper GI series with
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
76
Table 3. Algorithm of Postoperative Rehabilitation
At Cleveland Clinic Florida After Major Abdominal Surgery
Postoper-
ative Day Activity Comments
0 Oral/nasogastric tube removed at extubation
1
Enforced early postoperative mobilization 5 laps in the hallway (approximately 100 m)
Clear liquid diet, ice chips
Subcutaneous heparin; deep vein thrombosis
prophylaxis
5,000 units every 8 h
Incentive spirometry exercises Prevention of respiratory problems
2
Awaiting flatus or bowel movement
Removal of dressing
Removal of bladder catheter
3
If flatus or bowel movement has occurred, advance
diet to full liquid diet
Discontinue patient-controlled analgesia pump
Oral pain medication
4
Advance diet to low-residue diet, unless distended
Anticipate discharge home
Table 4. Definition of Diets
At Cleveland Clinic Florida
After Major Abdominal Surgery
Diet Foods Allowed, Only:
Clear liquid Broth, clear juices (apple, grape,
cranberry), coffee, tea, soda,
fruit ice, popsicle, sugar, salt
Clear liquid,
American Diabe-
tes Association
(diabetic)
Give regular clear liquid
Full liquid All items allowed on clear liq-
uid diet, plus pudding, strained
cream soups, oatmeal, cream of
rice, ice cream, sherbet, milk
Low residue Low fiber (avoid whole grains,
fresh fruits, and vegetables)
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
small bowel follow through and/or a computed tomog-
raphy scan with oral contrast might be useful in diag-
nosing, and potentially treating, obstruction. In these
cases, Gastrografin (Bracco Diagnostics, Inc.) may be
prokinetic.
59-65
Gastrografin has an osmolarity of 1,900
mOsm/L, which is approximately 6 times that of extra-
cellular fluid. It has been hypothesized that Gastrografin
promotes shifting fluid into the bowel lumen, decreas-
ing the pressure gradient across obstructive sites or
bowel lumen. After the Gastrografin is diluted it may
facilitate passage of contents within the intestinal track,
with decreased bowel wall edema. Unlike barium, Gas-
trografin is relatively safe even if intestinal perforation
and peritoneal spread occurs.
63,66,67

Conclusion
Despite significant advances in surgical and periop-
erative care, one of the most basic problems encoun-
tered in the postoperative period remains one of the
most vexing. POI remains an Achilles heel of abdomi-
nal surgery. It has been ill-defined, has been difficult to
characterize, and even harder to treat. Hopefully, some
of the new pharmacologic modalities and fast-track
protocols may help diminish this very troubling post-
operative problem.
References
HCUP Nationwide Inpatient Sample. Healthcare Cost and Utilization 1.
Project; 2006. http://hcupnet.ahrq.gov. Accessed April 24, 2009.
Matthaiou DK, Peppas G, Falagas ME. Meta-analysis on Surgical 2.
Infections. Infect Dis Clin North Am. 2009;23(2):405-430.
Byrnes MC, Beilman GJ. Adjunctive measures for treating surgical 3.
infections and sepsis. Surg Clin North Am. 2009;89(2):349-363.
Nichols RL. Preventing surgical site infections: a surgeons per- 4.
spective. Emerg Infect Dis. 2001;7(2):220-224.
Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2006 5.
guideline update on perioperative cardiovascular evaluation
for noncardiac surgery: focused update on perioperative beta-
blocker therapy: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines
(Writing Committee to Update the 2002 Guidelines on Periopera-
tive Cardiovascular Evaluation for Noncardiac Surgery) developed
in collaboration with the American Society of Echocardiography,
American Society of Nuclear Cardiology, Heart Rhythm Society,
Society of Cardiovascular Anesthesiologists, Society for Cardio-
vascular Angiography and Interventions, and Society for Vascular
Medicine and Biology. J Am Coll Cardiol. 2006;47(11):2343-2355.
Kehlet H. Postoperative ileusan update on preventive tech- 6.
niques. Nat Clin Pract Gastroenterol Hepatol. 2008;5(10):552-558.
Holte K, Kehlet H. Postoperative ileus: a preventable event. 7. Br J
Surg. 2000;87(11):1480-1493.
Artinyan A, Nunoo-Mensah JW, Balasubramaniam S, et al. Pro- 8.
longed postoperative ileus-definition, risk factors, and predictors
after surgery. World J Surg. 2008;32(7):1495-1500.
Lubawski J, Saclarides T. Postoperative ileus: strategies for reduc- 9.
tion. Ther Clin Risk Manag. 2008;4(5):913-917.
Maffezzini M, Campodonico F, Canepa G, et al. Current perioper- 10.
ative management of radical cystectomy with intestinal urinary
reconstruction for muscle-invasive bladder cancer and reduction of
the incidence of postoperative ileus. Surg Oncol. 2008;17(1):41-48.
Berend KR, Lombardi AV, Jr., Mallory TH, et al. Ileus following total 11.
hip or knee arthroplasty is associated with increased risk of deep
venous thrombosis and pulmonary embolism. J Arthroplasty.
2004;19(7 suppl 2):82-86.
Stany MP, Farley JH. Complications of gynecologic surgery. 12.
Surg Clin North Am. 2008;88(2):343-359.
Holte K, Kehlet H. Postoperative ileus: progress towards effective 13.
management. Drugs. 2002;62(18):2603-2615.
Delaney CP. Clinical perspective on postoperative ileus and the 14.
effect of opiates. Neurogastroenterol Motil. 2004;16(suppl 2):61-66.
Schein M, Sajja S. Postoperative Ileus vs Intestinal Obstruction. 15.
In: Schein M, Rogers PN, eds. Scheins common sense emergency
abdominal surgery. Berlin; New York: Springer; 2005:369-376.
Prasad M, Matthews JB. Deflating postoperative ileus. 16. Gastroen-
terology. 1999;117(2):489-492.
Person B, Wexner SD. The management of postoperative ileus. 17.
Curr Probl Surg. 2006;43(1):12-65.
Lewis SJ, Egger M, Sylvester PA, Thomas S. Early enteral feeding 18.
versus nil by mouth after gastrointestinal surgery:
systematic review and meta-analysis of controlled trials. BMJ.
2001;323(7316):773-776.
Reissman P, Teoh TA, Cohen SM, et al. Is early oral feeding safe 19.
after elective colorectal surgery? A prospective randomized trial.
Ann Surg. 1995;222(1):73-77.
20.Elwyn DH, Bryan-Brown CW, Shoemaker WC. Nutritional 20.
aspects of body water dislocations in postoperative and depleted
patients. Ann Surg. 1975;182(1):76-85.
Andersen HK, Lewis SJ, Thomas S. Early enteral nutrition within 21.
24h of colorectal surgery versus later commencement of feed-
ing for postoperative complications. Cochrane Database Syst Rev.
2006(4):CD004080.
Moore FA, Feliciano DV, Andrassy RJ, et al. Early enteral feed- 22.
ing, compared with parenteral, reduces postoperative septic
complications. The results of a meta-analysis. Ann Surg.
1992;216(2):172-183.
Binderow SR, Cohen SM, Wexner SD, Nogueras JJ. Must early 23.
postoperative oral intake be limited to laparoscopy? Dis Colon
Rectum. 1994;37(6):584-589.
Sarawate CA, Lin S-J, Walton SM, et al. Economic burden of post- 24.
operative ileus (POI) in abdominal surgical procedures.
Gastroenterology. 2003;124(4):A828.
Moss G, Regal ME, Lichtig L. Reducing postoperative pain, narcot- 25.
ics, and length of hospitalization. Surgery. 1986;99(2):206-210.
Woods MS. Postoperative ileus: dogma versus data from bench to 26.
bedside. Perspect Colon Rectal Surg. 2000;12:57-76.
Goldstein JL, Matuszewski KA, Delaney CP, et al. Inpatient eco- 27.
nomic burden of postoperative ileus associated with abdominal
surgery in the United States. P T. 2007;32(2):82-90.
Delaney CP, Senagore AJ, Viscusi ER, et al. Postoperative upper 28.
and lower gastrointestinal recovery and gastrointestinal mor-
bidity in patients undergoing bowel resection: pooled analysis
of placebo data from 3 randomized controlled trials. Am J Surg.
2006;191(3):315-319.
Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postop- 29.
erative recovery. Lancet. 2003;362(9399):1921-1928.
Litkouhi B, Muto MG. Postoperative ileus. In: Rose BA, editor: 30. Up-
To-Date. Waltham, MA: Available at www.uptodate.com. Accessed
July 29, 2009.
Braumann C, Guenther N, Wendling P, et al. Multimodal perioper- 31.
ative rehabilitation in elective conventional resection of colonic
cancer: Results from the German Multicenter Quality Assurance
Program Fast-Track Colon II. Dig Surg. 2009;26(2):123-129.
Wind J, Hofland J, Preckel B, et al. Perioperative strategy in 32.
colonic surgery; LAparoscopy and/or FAst track multimodal man-
agement versus standard care (LAFA trial). BMC Surg. 2006;6:16.
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
77
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.
Wind J, Polle SW, Fung Kon Jin PH, et al. Systematic review of 33.
enhanced recovery programmes in colonic surgery. Br J Surg.
2006;93(7):800-809.
Delaney CP, Zutshi M, Senagore AJ, et al. Prospective, ran- 34.
domized, controlled trial between a pathway of controlled
rehabilitation with early ambulation and diet and traditional post-
operative care after laparotomy and intestinal resection. Dis Colon
Rectum. 2003;46(7):851-859.
Kehlet H. Multimodal approach to control postoperative 35.
pathophysiology and rehabilitation. Br J Anaesth. 1997;78(5):
606-617.
Kehlet H, Wilmore DW. Evidence-based surgical care and the evo- 36.
lution of fast-track surgery. Ann Surg. 2008;248(2):189-198.
Rahbari NN, Zimmermann JB, Schmidt T, et al. Meta-analysis of 37.
standard, restrictive and supplemental fluid administration in col-
orectal surgery. Br J Surg. 2009;96(4):331-341.
De Schepper HU, Cremonini F, Park MI, Camilleri M. Opioids and 38.
the gut: pharmacology and current clinical experience. Neurogas-
troenterol Motil. 2004;16(4):383-394.
Kuo CP, Jao SW, Chen KM, et al. Comparison of the effects of tho- 39.
racic epidural analgesia and I.V. infusion with lidocaine on cytokine
response, postoperative pain and bowel function in patients
undergoing colonic surgery. Br J Anaesth. 2006;97(5):640-646.
Holte K, Kehlet H. Fluid therapy and surgical outcomes in elective 40.
surgery: a need for reassessment in fast-track surgery. J Am Coll
Surg. 2006;202(6):971-989.
Schwenk W, Haase O, Neudecker J, Muller JM. Short term bene- 41.
fits for laparoscopic colorectal resection. Cochrane Database Syst
Rev. 2005(3):CD003145.
Lindsetmo RO, Champagne B, Delaney CP. Laparoscopic rectal 42.
resections and fast-track surgery: what can be expected? Am J
Surg. 2009;197(3):408-412.
Tandeter H. Hypothesis: hexitols in chewing gum may play a role in 43.
reducing postoperative ileus. Med Hypotheses. 2009;72(1):39-40.
Matros E, Rocha F, Zinner M, et al. Does gum chewing ameliorate 44.
postoperative ileus? Results of a prospective, randomized, pla-
cebo-controlled trial. J Am Coll Surg. 2006;202(5):773-778.
Noble EJ, Harris R, Hosie KB, et al. Gum chewing reduces postop- 45.
erative ileus? A systematic review and meta-analysis. Int J Surg.
2009;7(2):100-105.
Parnaby CN, MacDonald AJ, Jenkins JT. Sham feed or sham? A 46.
meta-analysis of randomized clinical trials assessing the effect of
gum chewing on gut function after elective colorectal surgery. Int
J Colorectal Dis. 2009;24(5):585-592.
Vasquez W, Hernandez AV, Garcia-Sabrido JL. Is gum chewing 47.
useful for ileus after elective colorectal surgery? A systematic
review and meta-analysis of randomized clinical trials. J Gastroin-
test Surg. 2009;13(4):649-656.
Purkayastha S, Tilney HS, Darzi AW, Tekkis PP. Meta-analy- 48.
sis of randomized studies evaluating chewing gum to enhance
postoperative recovery following colectomy. Arch Surg.
2008;143(8):788-793.
de Castro SM, van den Esschert JW, van Heek NT, et al. A system- 49.
atic review of the efficacy of gum chewing for the amelioration of
postoperative ileus. Dig Surg. 2008;25(1):39-45.
Chan MK, Law WL. Use of chewing gum in reducing postoperative 50.
ileus after elective colorectal resection: a systematic review. Dis
Colon Rectum. 2007;50(12):2149-2157.
Tan KY, Liu CB, Chen AH, et al. The role of traditional Chinese 51.
medicine in colorectal cancer treatment. Tech Coloproctol.
2008;12(1):1-6; discussion 6.
Traut U, Brugger L, Kunz R, et al. Systemic prokinetic pharma- 52.
cologic treatment for postoperative adynamic ileus following
abdominal surgery in adults. Cochrane Database Syst Rev.
2008(1):CD004930.
Progenics and Wyeth Announce FDA has Approved Relistor. 53.
2008; First Drug for Opioid-Induced Constipation to Launch in
United States. http://www.wyeth.com/news?nav=display&navTo=/
wyeth_html/home/news/pressreleases/2008/1209080590441.
html. Accessed 4/27, 2009.
Cannom RR, Mason RJ. Methylnaltrexone: the answer to opi- 54.
oid-induced constipation? Expert Opin Pharmacother.
2009;10(6):1039-1045.
Lightfoot AJ, Eno M, Kreder KJ, et al. Treatment of postoperative 55.
ileus after bowel surgery with low-dose intravenous erythromycin.
Urology. 2007;69(4):611-615.
Narita K, Tsunoda A, Takenaka K, Watanabe M, et al. Effect of 56.
mosapride on recovery of intestinal motility after hand-assisted
laparoscopic colectomy for carcinoma. Dis Colon Rectum.
2008;51(11):1692-1695.
Kaba A, Laurent SR, Detroz BJ, et al. Intravenous lidocaine infu- 57.
sion facilitates acute rehabilitation after laparoscopic colectomy.
Anesthesiology. 2007;106(1):11-18; discussion 15-16.
Marret E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intra- 58.
venous lidocaine and postoperative recovery after abdominal
surgery. Br J Surg. 2008;95(11):1331-1338.
Burke MS, Ragi JM, Karamanoukian HL, et al. New strategies in 59.
nonoperative management of meconium ileus. J Pediatr Surg.
2002;37(5):760-764.
Schermer CR, Hanosh JJ, Davis M, Pitcher DE. Ogilvies syndrome 60.
in the surgical patient: a new therapeutic modality. J Gastrointest
Surg. 1999;3(2):173-177.
Biondo S, Pares D, Mora L, et al. Randomized clinical study of 61.
Gastrografin administration in patients with adhesive small bowel
obstruction. Br J Surg. 2003;90(5):542-546.
Assalia A, Schein M, Kopelman D, et al. Therapeutic effect of oral 62.
Gastrografin in adhesive, partial small-bowel obstruction: a pro-
spective randomized trial. Surgery. 1994;115(4):433-437.
Di Saverio S, Catena F, Ansaloni L, et al. Water-soluble contrast 63.
medium (gastrografin) value in adhesive small intestine obstruc-
tion (ASIO): a prospective, randomized, controlled, clinical trial.
World J Surg. 2008;32(10):2293-2304.
Zhang Y, Gao Y, Ma Q, et al. Randomised clinical trial investigating 64.
the effects of combined administration of octreotide and meth-
ylglucamine diatrizoate in the older persons with adhesive small
bowel obstruction. Dig Liver Dis. 2006;38(3):188-194.
Burge J, Abbas SM, Roadley G, et al. Randomized controlled trial 65.
of Gastrografin in adhesive small bowel obstruction. ANZ J Surg.
2005;75(8):672-674.
Chen SC, Chang KJ, Lee PH, et al. Oral urografin in postoperative 66.
small bowel obstruction. World J Surg. 1999;23(10):1051-1054.
Choi HK, Chu KW, Law WL. Therapeutic value of gastrografin 67.
in adhesive small bowel obstruction after unsuccessful con-
servative treatment: a prospective randomized trial. Ann Surg.
2002;236(1):1-6.
I NDEPENDENTLY DEVELOPED BY MCMAHON PUBLI SHI NG
78
C
o
p
y
r
i
g
h
t

2
0
0
9

M
c
M
a
h
o
n

P
u
b
l
i
s
h
i
n
g

G
r
o
u
p

u
n
l
e
s
s

o
t
h
e
r
w
i
s
e

n
o
t
e
d
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.

R
e
p
r
o
d
u
c
t
i
o
n

i
n

w
h
o
l
e

o
r

i
n

p
a
r
t

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n

i
s

p
r
o
h
i
b
i
t
e
d
.