Open Journal of Urology, 2013, 3, 272-275
Published Online November 2013 (http://www.scirp.org/journal/oju)
Open Access OJU
A Preliminary Investigation: Alvimopan Use to Prevent
Post-Operative Ileus after Radical Cystectomy with
Benjamin F. Katz1*, Geoffrey S. Gaunay1, Basir U. Tareen2, Erik T. Goluboff1
1Department of Urology, Beth Israel Medical Center, New York, USA
2Department of Urology, Metropolitan Urologic Associates, Woodbury, USA
Received July 30, 2013; revised August 28, 2013; accepted September 5, 2013
Copyright © 2013 Benjamin F. Katz et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Background: Postoperative ileus (POI) is a common and frustrating patient complication after a urinary diversion by
using a segment of bowel. Alvimopan is an oral selective antagonist to the peripheral µ-opioid receptor. Our study in-
vestigates the effect of alvimopan on POI in patients undergoing radical cystectomy. There are no documented studies
on alvimopan’s efficacy in urologic surgery literature. Methods: Approval from the Institutional Review Board was
obtained to conduct a retrospective review of patients’ records from August 2009 until August 2011. The study included
sixteen patients who had undergone radical cystectomy with ileal diversion. Exclusion criteria included patients with
chronic opioid use, previous colostomy or ileostomy, or significant comorbidities which could cause increased postop-
erative complications. Statistical analysis was performed to examine the association of alvimopan use with decreased
time to dietary advancement and decreased length of hospital stay. Results: The alvimopan group advanced their diet
more than 24 hours earlier in comparison with the alvimopan naïve group (P < 0.0433), and the alvimopan group had a
greater had a greater or 26% shorter hospital length (P < 0.0451) than one day. We showed a reduced risk of POI and
subsequent decreased hospital course length. There was no significant difference in readmission rate or need for na-
sogastric tube (NGT). Interpretation: To our knowledge we report one of the first uses of alvimopan in reducing POI
in the urological surgery literature. Our novel experience with using this drug is encouraging. Further research will ul-
timately determine if standard use of alvimopan to decrease POI in radical cystectomy with ileal diversion will be
Keywords: Cystectomy; Urinary Diversion; Alvimopan; Ileus
In 2009, there were over 70,000 new diagnoses of blad-
der cancer and more than 14,000 deaths, making bladder
cancer the 5th most common malignancy in the United
States . Although chemotherapy and radiation therapy
are options for select patients, the gold standard for mus-
cle invasive disease continues to be radical cystectomy
with urinary diversion. Reconstruction of the urinary
tract is a necessity in order to preserve renal function.
There are numerous diversions and reconstructions de-
scribed in the literature and most require the use of small
or large bowel.
Radical cystectomy continues to be a morbid proce-
dure fraught with complications. Ileus is a common oc-
currence leading to patient discomfort and increased
length of hospital stay . Post-operative ileus (POI) is
defined as a “transient impairment of bowel motility” .
This condition may lead to nausea, vomiting, prolonged
hospital stay, bowel distention, abdominal pain, and, in
severe cases, aspiration [3,4]. POI may also lead to re-
admission and more expensive hospital stays costing over
$4000 ($4118 - $8785) . The overall healthcare costs
from POI in the United States are estimated to be over
$1.46 billion annually .
It has been hypothesized that POI is caused by both an
inflammatory as well as a neural process. However, the
B. F. KATZ ET AL. 273
process is multifactorial. The inflammatory response is
believed to be directly related to surgical injury of the
viscera triggering an immunologic response, and the
complex neural process involves the somatic, adrenergic,
and endogenous stress mediated pathways . Opioid
use has been shown to exacerbate POI. The peripheral
µ-opioid receptor on the gastrointestinal tract has been
found to be a main contributory factor to POI when the
receptor is activated. By using opioid for post-surgical
pain control, the µ-receptor activation can lead to in-
creased colonic muscle tone and decreased peristalsis in
the GI tract .
Alvimopan is an oral selective antagonist to the pe-
ripheral µ-opioid receptor. Due to alvimopan’s large size,
zwitterionic form, and polarity, alvimopan does not cross
the blood-brain barrier, therefore allowing opioid central
analgesia . Alvimopan has been shown to lower the
incidence of nasogastric tube insertion postoperatively,
and decrease POI and subsequently decrease hospital
stay by approximately one day [8,9]. The efficacy and
safety of the 12 mg oral dose has been well described in
the gastrointestinal and gynecologic surgery literature.
In the present study, our aim was to investigate the ef-
fect of alvimopan on POI in patients undergoing radical
cystectomy. Tolerance of a clear liquid diet and hospital
length of stay were used as surrogate markers for bowel
function. There are no documented studies on alvimo-
pan’s efficacy in urologic surgeries.
2. Material and Methods
Approval from the Institutional Review Board was ob-
tained to conduct a retrospective review of patients’ re-
cords from August 2009 until August 2011. The study
included sixteen patients who had undergone radical cys-
tectomy with ileal diversion. Exclusion criteria included
patients with chronic opioid use, previous colostomy or
ileostomy, or significant comorbidities which could cause
increased postoperative complications. The 16 patients
were consecutive cases performed by two different surgeons
in one institution; no patients were excluded in the trial.
All patients had their complete hospital medical re-
cords and preoperative evaluation reviewed. Patients’ de-
mographics included age, sex, race, BMI, procedure,
morbidities, need for nasogastric tube, days until clear li-
quids, length of stay, surgeon and use of alvimopan were
evaluated. For the purpose of this study, morbidities were
defined as any inpatient serious adverse events or read-
mission within 30 days postoperatively.
The cystectomy postoperative pathway in our patients
includes pain management, encouragement of early am-
bulation, incentive spirometry and advancing the patient
to a clear liquid diet once flatus is reported. Patients were
separated into two arms; alvimopan 12 mg and alvimo-
pan naïve. The alvimopan arm was given 12 mg orally 1
to 2 hours preoperatively in the preoperative holding area
and continued on alvimopan 12 mg twice daily until dis-
Statistical analysis was performed to examine the as-
sociation of alvimopan use with decreased time to dietary
advancement and decreased length of hospital stay. Uni-
variante analysis was obtained with P < 0.05. All statis-
tical tests were achieved using Stata (College Station,
TX), version 12.
Sixteen consecutive patients were identified during the
allocated time period and all 16 patients were included in
our study. Of the 16 patients, 8 received alvimopan and 8
were alvimopan naïve. Mean patient age was 63.5 (range
46 to 78) and mean body mass index was 26 kg/m² (range
17 to 37). There were 4 females (25%) and all cases were
radical cystectomy with ileal noncontinent conduit. The
majority of the patients were Caucasian (56%), followed
by Asian (19%) and Hispanic (19%).
According to Table 1, the naïve arm was younger and
had a lower BMI as compared to the alvimopan group,
which had five patients over the age of 65 compared to
just one in the naïve group. The race and gender of the
two groups were similar. The alvimopan patients had
significantly less POI as compared to the alvimopan na-
ïve arm. Statistical significance was achieved with a P
value 0.0433 when comparing the two arms for advan-
cement to a clear liquid diet. The median time to a clear
liquid diet was 3 days versus 4.1 days in the alvimopan
group versus the naïve group, respectively. The hospital
course was shorter as well, with the alvimopan group
going home in a mean of 5.1 days versus 6.9 days
Table 1. Baseline patient demographics.
Demographics Naïve (n = 8) Alvimopan (n = 8)
Mean ± SD 60.4 ± 7.8 66.6 ± 10.1
≥65, n (%) 1 (13%) 5 (63%)
Race, n (%)
Caucasian 5 (63%) 4 (50%)
Asian 1 (13%) 2 (25%)
Hispanic 2 (25%) 1 (13%)
African American 0 1 (13%)
Gender, n (%)
Female 2 (25%) 2 (25%)
Mean ± SD 24.9 ± 5.8 27.8 ± 3.6
≥30, n (%) 1 (13%) 2 (25%)
*BMI, body mass index; calculated as kg/m².
Open Access OJU
B. F. KATZ ET AL.
in the naïve group (Table 2). This variable also reached
statistical significance with a P value of 0.0451.
The readmission rate also favored the alvimopan group,
with two patients being readmitted for an infection and
bleeding duodenal ulcer (Clavien Classification II and I
respectively). The control group had four out of eight
patients readmitted within 30 days for 2 fevers and 2
abscess formation requiring intervention (Clavien Classi-
fication II and III respectively). It was expected that the
naïve group would have less complications due to their
younger age and lower BMI. None of the patients in ei-
ther group were readmitted for POI, small bowel ob-
struction or failure to thrive. Nasogastric tube insertion
was zero in both arms of the study.
Post-operative ileus is a very expensive and frustrating
condition that affects many post-surgical patients. No
research on the use of alvimopan in preventing POI has
been reported in the urologic literature. This initial study
is the first report of alvimopan use in urologic surgery.
By starting 12 mg alvimopan prior to surgery and sub-
sequently prior to opioid use, our goal was to block the
µ-opioid receptors and diminish POI. Statistical signifi-
cance was achieved in our limited sample size for both
key factors in POI. The alvimopan group advanced their
diet more than 24 hours earlier in comparison to the al-
vimopan naïve group, and the alvimopan group had a
greater than one day or 26% shorter hospital length. We
showed a reduced risk of POI and subsequent decreased
hospital course length.
According to Bell and colleagues, a hospital day costs
an estimated $1300 to $1600 a day for a bowel resection
procedure. The $62.50 per dose of alvimopan if extrapo-
lated out to a five day hospital course would be equiva-
lent to around ten doses . This cost, although not in-
significant, pales in comparison to one or more days in
the hospital. The Bell study goes on to state that the total
hospital savings was averaged to “$977 less for patients
who received alvimopan . Our study had a greater
Table 2. Alvimopan versus control outcomes.
Naïve (n = 8) Alvimopan (n = 8)P Value
Days until PO order
Mean ± SD 4.1 ± 1.5 3 ± 0.9 0.0433
NGT placed, n
Hospital Length Days
Mean ± SD 6.9 ± 2.9 5.1 ± 1.2 0.0451
Readmission 30 Days
n (%) 4 (50%) 2 (25%)
than one and half day shorter hospital course and a much
sooner time to bowel recovery.
The use of alvimopan has been described in the gen-
eral surgery and gynecology literature for the prevention
of ileus [4,10]. According to Herzog et al., a dou-
ble-blind placebo controlled randomized trial using
alvimopan in female patients undergoing total abdominal
hysterectomy which did not resect bowel resulted in first
bowel movement 22 hours earlier and a safety profile
similar to placebo . Our patients did not report any
allergies or adverse reactions; however, our study design
was not specifically designed to look at such results.
The naïve group had an estimated four days until the
patient’s diet was advanced on the report of flatus. Mul-
tiple other novel concepts have been reported to hasten
bowel recovery time. Erythromycin and early removal of
a nasogastric tube was not shown to improve time to
bowel sounds, flatus, passage of first bowel movement or
prevention of ileus [11,12]. Pruthi and colleagues de-
scribed a perioperative care plan involving, but not lim-
ited to, restricting bowel preparation, reducing incisional
length, and limiting narcotic analgesics. The study
showed a significant improvement from 1996-1997 of
mean time to clear liquid diet starting at 6.9 baseline and
improving to 2.0 days in the 2001-2002 current pathway
. Perhaps the easiest and least expensive attempt to
shorten POI has been shown in gum chewing studies.
Kouba study and Choi study both found gum chewing to
improve time to flatus by 0.5 days [13,14]. Our study
found time to flatus and advancement of diet by more
than a day, and unlike the Kouba study, we found a sig-
nificant decrease in hospital length of stay. Choi did not
report data on length of hospital stay.
The alvimopan group had a slightly higher BMI and
age as compared to the controls. Increasing BMI and age
are “independent risk factors for the development of
postoperative paralytic ileus after radical cystectomy”
according to Svatek et al. . They report POI in 10%
of “normal” weight patients (BMI 18.5 - 24.9 kg/m²) and
POI in 22.2% and 30.3% in BMI 30 - 34.9 kg/m² and
≥35 kg/m² respectively. Svatek et al. did not show a dif-
ference in POI when comparing EBL, need for blood
transfusion, operative time, the type of urinary diversion,
or use of epidural anesthesia . Our alvimopan group
had a higher BMI (27.8 vs 24.9) and a higher age cohort
(66.6 vs. 60.4) as compared with the controls. One would
postulate that the alvimopan group should have a higher
rate of POI, but this was not the case. Statistical signifi-
cance was still obtained in our experimental arm.
This is one of the first reports of the use of alvimopan
in the urologic surgery literature to date to our knowl-
edge. There are limitations to this study. The limited
sample size poses a selection and sample bias. We were
able to show statistical significance; however, to deter-
Open Access OJU
B. F. KATZ ET AL.
Open Access OJU
mine the true impact of the results, the study should be
conducted on a much larger scale. The retrospective,
nonrandomized, single institution design implores us to
study this drug further. This initial report was intended to
show a preliminary trend towards decreasing the morbid-
ity of POI in radical cystectomy with ileal diversion by
using the drug alvimopan. Further and more detailed re-
search is evidently needed to decipher objectively the use
of alvimopan in urologic procedures.
To our knowledge we report one of the first uses of alvi-
mopan in reducing POI in the urological surgery litera-
ture. Our novel experience with using this drug is en-
couraging. Further research will ultimately determine if
standard use of alvimopan to decrease POI in radical
cystectomy with ileal diversion will be implemented.
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