EUROPEAN UROLOGY 64 (2013) 588–597

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Platinum Priority – Review – Bladder Cancer

Editorial by Mathew C. Raynor and Raj S. Pruthi on pp. 598–599 of this issue

Definition, Incidence, Risk Factors, and Prevention of Paralytic

Ileus Following Radical Cystectomy: A Systematic Review

Jorge A. Ramirez a, Andrew G. McIntosh a, Robert Strehlow a, Valerie A. Lawrence b,

Dipen J. Parekh a, Robert S. Svatek a,*
a
Department of Urology, The University of Texas Health Science Center San Antonio, San Antonio, TX, USA; b Department of Medicine, The University of Texas
Health Science Center San Antonio, San Antonio, TX, USA

Article info Abstract

Article history: Context: Postoperative paralytic ileus (POI) has profound clinical consequences because
Accepted November 27, 2012 it represents a substantial burden on both patients and health care resources.
Published online ahead of Objective: To determine the knowledge base regarding POI in the radical cystectomy
(RC) population with an emphasis on preventive measures and risk factors.
print on December 5, 2012 Evidence acquisition: A systematic literature search of Medline (1966 to February 2011)
and a study review were conducted. Eligible studies explicitly reported the incidence of
Keywords: POI and/or at least two quantitative measures of gastrointestinal recovery.
Evidence synthesis: The search identified 727 relevant articles; 77 met eligibility criteria,
Cystectomy
comprising 13 793 patients. Of these, 21 used explicit definitions of POI, and they varied
Ileus widely. Across studies, the incidence of POI ranged from 1.58% to 23.5%. Possible risk
Review factors for POI included increasing age and body mass index. Seventeen studies reported
effects of an intervention on POI: 3 randomized controlled studies, 11 observational
cohort studies with concurrent comparison, and 3 observational cohort studies with
nonconcurrent comparison. Gum chewing was associated with shortened times to flatus
(2.4 vs 2.9 d; p < 0.0001) and bowel movement (BM) (3.2 vs 3.9 d; p < 0.001) in one
observational cohort study (n = 102); omission of a postoperative nasogastric tube (NGT)
was associated with shorter time to flatus (4.21 vs 5.33 d; p = 0.0001) and shorter length
of stay (14.4 vs 19.1 d; p = 0.001) in one observational cohort study (n = 430); and the
routine use of bowel preparation was associated with an increased incidence of POI (5%
vs 19%) in another series (n = 86). Additionally, readaptation of the dorsolateral perito-
neal layer was shown to shorten times to flatus ( p = 0.016) and times to BM ( p = 0.011) in
one randomized controlled study (n = 200).
Conclusions: The incidence/definition of POI after RC is highly variable. An improved
reporting strategy is needed to identify true incidence and risk factors, and to guide
future research for both potential preventive and therapeutic interventions.
# 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Department of Urology, Division of Urologic Oncology, The University of

Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Tel. +1 210 567 5676; Fax: +1 210 567 6868.
E-mail address: svatek@uthscsa.edu (R.S. Svatek).

1. Introduction high complication rate [1–3]. One of the most common

complications is postoperative paralytic ileus (POI) [2–5].
Despite major improvements in perioperative patient care, Transient cessation of bowel activity is expected following
radical cystectomy (RC) continues to be associated with a major abdominal surgery with small bowel motility and
0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.eururo.2012.11.051
 EUROPEAN UROLOGY 64 (2013) 588–597
gastric emptying returning quite quickly (within 24 and
48 h, respectively). Large bowel recovery, however, is
typically more protracted, taking up to 3–5 d to resume
activity [6,7]. Despite the expectation of diminished
intestinal motility following surgery, the period without
signs of bowel function often extends beyond what is
acceptable and is then diagnosed as POI.
POI has been mainly studied in patients undergoing
general abdominal surgery. It has been shown to prolong
the length of stay (LOS) by days to weeks and is associated
with increased morbidity and costs [8–10]. Estimates of
incidence vary in the general surgery literature, and clinical
trials have been conducted to identify strategies to prevent
POI. A meta-analysis of the effect of postoperative gum
chewing revealed a decrease in the rate of POI and LOS [11].
A Cochrane review of the effect of prokinetic agents on POI
found that certain medications reduce time to flatus and
duration of hospital stay [12]. Epidural anesthesia, in
contrast to opiate use, was found to reduce POI but not
length of hospital stay [13]. Alvimopan, a peripherally
acting m-opioid receptor antagonist, was found to reduce
time to flatus as well as accelerate time to hospital
discharge [14]. Finally, early commencement of oral fluids
has been shown to reduce time to bowel sounds and solid
diet intake and has demonstrated improvement toward
shorter hospital stays [15].
To improve our understanding of POI as it relates
specifically to RC patients, we conducted a systematic
review of the evidence base on POI for patients undergoing
RC. We sought to capture the reported incidence of POI,
interventions to prevent POI, and risk factors for POI among
RC populations. We also include standardized care path-
ways that, although they do not examine a specific
intervention, have similarly been used to optimize gastro-
intestinal (GI) recovery and/or the incidence of POI.
2. Evidence acquisition
We conducted a systematic review of Medline from 1966 to
February 2011 in adherence with the Preferred Reporting
Items for Systematic Reviews and Meta-analysis guidelines
[16] using the following search criteria:
1. Medical Subject Headings (MeSH) terms: cystectomy,
preoperative care or intraoperative care or postoperative
care or perioperative care or postoperative period or
intraoperative complications or postoperative complications
2. Ovid text word terms: preoperative care or intraoperative
care or postoperative care or perioperative care or
postoperative period or intraoperative complications or
postoperative complications
3. Linkage: Items 1 and 2, limited to human adults and
publications in English
We then conducted an additional search for additional
articles using only the following text word terms: cystectomy
and ileus. We specifically used Ovid text word terms for the
perioperative period to maximize the sensitivity of the search
strategy. Studies reviewed were limited to those that
589
reported primary data. To be eligible for inclusion, studies
had to report one or more of the following: (1) incidence of
POI using an explicit definition or at least two quantitative
measurements of GI recovery including LOS, time to bowel
sounds, time to flatus, time to bowel movement (BM), time to
liquid diet/oral intake, time to regular diet; (2) potential risk
factors for the development of POI; and (3) interventions to
prevent or limit the incidence or duration of POI. Data from
cohorts represented in more than one publication were
only reported once. Exclusion criteria were studies with
<10 patients, case reports, or those studies not reporting any
data on POI or GI recovery.
Study quality and methodology for randomized con-
trolled trials (RCTs) was assessed using the Jadad scale [17]
and the Consolidated Standards for Reporting Trials
(CONSORT) statement [18]. In the Jadad scale, a maximum
score of 5 points (2 for randomization, 2 for blinding, and 1
for accountability of all patients) can be attained, and an
overall score 3 indicates a high-quality study [17]. In the
CONSORT scale, a 22-item checklist receives 0–2 points
depending on the quality of the description (0 = no
description, 1 = inadequate description, 2 = adequate de-
scription). In observational cohort studies, quality was
assessed using the Newcastle-Ottawa scale [19], where
studies are given up to 9 total points for meeting criteria in
selection, comparability, and exposure. We considered
studies as high quality if they received 8 or 9 points,
medium quality if they received 6 or 7 points, and low
quality if they received 5 points [19].
3. Evidence synthesis
3.1. Overview
Initially, our search yielded 727 potentially relevant
publications (Fig. 1). The titles of all 727 results were
reviewed, and if the publication could not be eliminated
based on title alone, the abstract was subsequently
reviewed. The remaining 332 manuscripts were reviewed
in full to determine eligibility. A total of 77 articles
contained data in accordance with the eligibility criteria.
From these 77 articles, we identified 13 793 patients who
underwent RC and who were noted to have experienced or
not experienced POI in the postoperative period. We
identified studies that did not explicitly identify patients
with POI but did note various indicators of the return of
bowel function according to our criteria.
3.2. Incidence of postoperative paralytic ileus
Of the 77 studies, 68 reported the incidence of POI. The rate
of POI for cystectomy patients varied from 1.58% to 23.5%
with an average rate of POI of 9.86% for 13 793 patients.
3.3. Definitions of postoperative paralytic ileus
The definition for POI varied among reports. Only 21 of the
77 studies meeting initial search criteria used explicit
definitions of POI. Among RCTs, no definition of POI was
590 EUROPEAN UROLOGY 64 (2013) 588–597
[(Fig._1)TD$IG]
Initial Search: n = 727
(All potentially relevant articles reviewed
by title initially; abstracts reviewed if
necessary to rule out relevance)
n = 332; Remaining Articles
(All abstracts reviewed for relevance
and manuscript reviewed if needed to
rule out relevance)
n = 77; Manuscripts Reviewed in full
(Contain data meeting search criteria)
Fig. 1 – Flow diagram of the number of articles identified at each step of the systematic literature research. POI = postoperative paralytic ileus.
identified. Within observational cohort studies with con-
current controls, definitions included no return of bowel
function after postoperative day (POD) 6 [20]; absence of
flatus or stool on POD 6 [21,22]; absence of bowel function
after POD 5 [23,24]; and postoperative nausea or vomiting
requiring cessation of oral intake, intravenous support, or
NGT placement by POD 5 [25,26]. Within observational
cohort studies with nonconcurrent controls, definitions
included absence of bowel function beyond POD 4 [27];
return of bowel function after POD 5 [28]; absence of flatus
and/or bowel movement prolonging hospitalization beyond
discharge goal of POD 6–8 [2]; no evidence of bowel
function beyond the anticipated discharge goal of 6 d [29];
lack of bowel activity >5 d following surgery [3]; and
inability to tolerate food by POD 5, the need to place a NGT,
or the need to stop oral intake due to abdominal distension,
nausea, or emesis [30].
3.4. Risk factors for development of postoperative paralytic
ileus
There are few observational cohort studies that identify
specific demographic or perioperative risk factors associat-
ed with the development of POI in RC patients. Svatek and
colleagues [29] identified increasing age and body mass
index (BMI) as risk factors for POI in an observational cohort
study (25.6% of patients with a BMI 30 kg/m2 experienced
POI compared with 11.3% of patients with a BMI <30 kg/m2;
p = 0.005). Lee and colleagues [31] observed that increasing
BMI is significantly associated with an increased incidence
of POI. In addition to increasing age, Hollenbeck and
colleagues [3] noted a history of dyspnea, general anesthe-
sia (vs spinal anesthesia), and increasing operative time to
Exclusions (n = 395):
1. Case reports
2. Case series <10 patients
3. Not a study on radical
cystectomy
4. Functional/physiologic
data only; surgical atlas
only
Exclusion (n = 255):
1. Redundant data from
previously reviewed
study
2. Does not report on POI
or other criteria
be risk factors for the development of POI. Yamanaka and
colleagues [32], however, found no significant difference in
POI among patients 80 yr of age (n = 72) compared with
patients <80 yr (n = 557) in a cohort of RC patients. Chang
and colleagues [2] demonstrated that ethnic minority, the
existence of another major complication, and blood loss
>600 ml were all significantly related to POI.
3.5. Interventions to reduce postoperative paralytic ileus
3.5.1. Randomized controlled trials
We identified three RCTs that studied a perioperative
intervention on RC patients and reported data according to
our criteria (Table 1). Both robot-assisted laparoscopic
radical cystectomy (RALRC) and readaptation of the perito-
neum were found to hasten the return of bowel function.
RALRC was found to have shorter times to flatus (2.3 vs 3.2 d;
p < 0.0001) and BM (3.2 vs 4.3 d; p = 0.0008) when compared
with open radical cystectomy (ORC) (n = 41) [33]. Read-
aptation of the dorsolateral peritoneal layer was shown
(n = 200) to shorten times to flatus (reaching statistical
significance on POD 3; p = 0.016) and times to BM (95% vs 84%
had BM by POD 7; p = 0.011) [34]. Treatment with
erythromycin, a prokinetic agent, showed no difference in
bowel recovery compared with controls (n = 22) [35]. None of
the three trials report explicitly on the incidence of POI.
3.5.2. Observational cohort with concurrent comparison
We additionally identified 11 observational cohort studies
with concurrent comparison groups that reported data on
POI or GI recovery (Table 2). Of the 11 studies, only 4
reported explicitly on the difference in POI rates between
cohorts.
 EUROPEAN UROLOGY 64 (2013) 588–597 591

Table 1 – Randomized controlled trials

Study Definition No. of Intervention/ Results Conclusion Study

of ileus patients Comparison appraisal
*
Lightfoot Not defined 22; 11 received Postoperative erythromycin Median times, (+) vs ( ), Erythromycin is CONSORT score
et al. [35] erythromycin (+); therapy following ORC to normal diet (9 d vs 8 d; not useful in (30/44)
**
11 controls ( ) p = 0.60), bowel sounds reduction of POI Jadad score (5/5)
(2 d vs 3 d; p = 0.88), and
BM (6 d vs 5 d; p = 0.98)
not significantly different
*
Nix Not defined 41; 21 robotic Noninferiority study of RALRC Median times to: flatus Robotic approach CONSORT score
et al. [33] technique; compared with ORC (2.3 d vs 3.2 d; p < 0.0001) compares favorably (33/44)
**
20 open and to BM (3.2 d vs 4.3 d; with open approach Jadad score (2/5)
technique p = 0.0008) significantly for several perioperative
decreased in RALRC group measures including
recovery of bowel
function
*
Roth Not defined 200; 100 had the Bilateral readaptation of Times to flatus earlier in (+) Readaptation of the CONSORT score
et al. [34] peritoneum dorsolateral peritoneal layer group and reached statistical peritoneum following (32/44)
**
readapted by creating lateral flaps of significance ( p = 0.016) on radical cystectomy Jadad score (3/5)
bilaterally (+); peritoneum when accessing POD 3; 95% of (+) group vs hastens postoperative
100 controls the retroperitoneal space and 84% of ( ) group passed recovery of bowel
did not ( ) fixing them to the medial stool by POD 7 ( p = 0.011) function
peritoneal layer following ORC

BM = bowel movement; ORC = open radical cystectomy; POD = postoperative day; RALRC = robot-assisted laparoscopic radical cystectomy.
(+) received treatment; ( ) served as control.
*
CONSORT (Consolidated Standards of Reporting Trials) score: 22-item validated tool; maximum 44 points; score for each item: 0 = no description,
1 = inadequate description, 2 = adequate description.
**
Jadad score: Maximum score of 5 points (2 for randomization, 2 for blinding, and 1 for accountability of all patients) with an overall score 3 indicating a
high-quality study.

Both laparoscopic RC (LRC) and RALRC were associated
with hastened return of bowel function when compared
with ORC. Guillotreau and colleagues [23] demonstrated
that LRC was associated with a lower incidence of POI (11 vs
30%; p = 0.043), shortened times to oral food intake (3.8 vs
6.4 d; p = 0.043), and shortened LOS (2.1 vs 4.4 d; p = 0.009)
when compared with ORC (n = 68). Although they did not
report on the incidence of POI between groups, two studies
[36,37] supported these findings, noting decreased times to
oral intake in the LRC group (3.3 vs 5.7 d; p < 0.05, and 2.8 vs
5 d; p = 0.004, respectively) compared with the ORC group
(n = 42 and n = 24, respectively). Additionally, one study
[38] demonstrated that RALRC was associated with shorter
times to regular diet (4 vs 5 d; p = 0.002) and LOS (5 vs 8 d;
p = 0.007) when compared with ORC (n = 54).
Both prolonged use of NGT decompression and routine
bowel preparation were associated with exacerbated times
to bowel recovery. A large study by Inman and colleagues
[22] demonstrated that prolonged NGT tube decompression
was associated with prolonged time to GI recovery. In this
study, which included 430 patients, omission of routine
NGT decompression after RC, compared with prolonged
nasogastric decompression, was associated with shorter
times to return of bowel sounds (1.99 vs 2.44 d; p = 0.0001),
time to flatus (4.21 vs 5.33 d; p = 0.0001), and LOS (14.4 vs
19.1 d; p = 0.001). However, the incidence of POI was not
significantly different between groups. When combined
with postoperative metoclopramide in a study by Donat and
colleagues [39] (n = 81), NGT omission was again associated
with improved GI recovery according to similar parameters.
Park and colleagues [21] did not show a significant decrease
in the incidence of POI with early NGT removal; however,
they did demonstrate a higher risk of POI in those who had
polyethylene glycol bowel preparation versus sodium
phosphate (40% vs 18%; p = 0.02; n = 101). Shafii and
colleagues [40] demonstrated a lower incidence of POI
(5% vs 19%), shorter LOS (22.8 vs 31.6 d), and time to oral
fluids (3.4 vs 5.8 d) when preoperative bowel preparation
was omitted altogether (n = 86).
With regard to the potential influence of urinary
diversion type on POI rates, Parekh and colleagues [41]
found a higher incidence of POI in their ileal conduit
versus ileal neobladder group (7.4% vs 2.6%). Conversely,
Nieuwenhuijzen and colleagues [42] did not observe a
difference in POI incidence between ileal conduit, Indiana
pouch, and neobladder in their series. The specific effect of
this variable on POI remains less clear.
3.5.3. Observational cohort with nonconcurrent comparison
We identified three observational cohort studies with
nonconcurrent comparisons, only one of which explicitly
reported the incidence of POI (Table 3). Both gum chewing
and the use of RALRC were associated with earlier GI
recovery. Kouba and colleagues [43] demonstrated an
association between postoperative gum chewing and
shorter times to flatus (2.4 vs 2.9 d; p < 0.0001) and BM
(3.2 vs 3.9 d; p < 0.001) when compared with those patients
not receiving gum following RC (n = 102). Additionally,
Abraham and colleagues [44] (n = 34) found an association
between RALRC, compared with LRC, and shorter times to
oral intake (2.3 vs 6.1; p = 0.012) and regular diet (3.7 vs 7.0;
p = 0.011). Combining these findings with that of the
previous section, it appears that RALRC is associated with
hastened GI recovery when compared with both LRC and
 592
Table 2 – Observational cohort with concurrent comparison

Study Definition of ileus No. of patients Intervention/comparison Results Conclusion Study appraisal
*
Park et al. [21] Absence of flatus 101; 20 had NGT removed Early NGT removal in patients POI in 23 patients (23%); rate of Early NGT removal is not associated Newcastle-Ottawa
or stool at POD 6 within 24 h of surgery (+); compared with prolonged NGT POI in (+) vs ( ) groups not with a decrease in POI; however, Scale (8/9)
(additionally, if 81 had NGT removed at decompression following open significantly different use of sodium phosphate for bowel
patients experienced first flatus ( ) radical cystectomy (25% vs 22%); risk of POI higher prep may reduce incidence of POI
nausea, emesis, or gas in those who had polyethylene
distention of abdominal glycol bowel prep vs sodium
x-ray, they were phosphate (40% vs 18%; p = 0.02)
considered to have ileus)
*
Inman et al. [22] Absence of flatus 430; 199 did not receive Effect on GI complications of Mean times to: return of BS NGT decompression after RC with Newcastle-Ottawa
or stool on POD 6 postoperative NGT (+); omission of NGT decompression (1.99 d vs 2.44 d; p = 0.0001), UD may prolong GI recovery, Scale (7/9)
221 received postoperative compared with patients who return of flatus (4.21 d vs increasing hospital stay and should
NGT ( ) received NGT decompression 5.33 d; p = 0.0001), and LOS not be used routinely
following ORC (14.4 d vs 19.1 d; p = 0.001)
shorter in ( ) group; POI

EUROPEAN UROLOGY 64 (2013) 588–597

incidence not significantly different
*
Donat et al. [39] Not defined 81; 27 received metoclopramide Effect of omission of NGT Times to return of normal bowel The combination of early NG Newcastle-Ottawa
combined with early NGT decompression and administration sounds (2.9 d vs 4.0 d; p = 0.0002) removal and metoclopramide may Scale (9/9)
removal (+); 54 received no of metoclopramide on GI recovery and resumption of solid diet hasten return of bowel function
metoclopramide and had compared with controls (6.7 d vs 7.9 d; p = 0.04) shorter
prolonged NGT decompression ( ) in the (+) group.
*
Shafii et al. [40] Not defined 86; 22 received no bowel Effect of omission of preoperative Incidence of POI lower in (+) Routine bowel preparation is Newcastle-Ottawa
preparation (+); 64 received bowel preparation on GI group (5% vs 19%) associated with increased hospital Scale (7/9)
standard bowel preparation ( ) complications compared with LOS (22.8 d vs 31.6 d) and time to stay and POI; it does not improve
controls who received preoperative fluids (3.4 d vs 5.8 d) both shorter surgical outcome
bowel preparation prior to ORC in (+) group
*
Wang et al. [47] Not defined 51; 31 had HALRC; 20 had LRC Clinical outcomes of HALRC LOS longer in LRC than HALRC LOS was significantly lower in Newcastle-Ottawa
compared with controls (19.7 d vs 24.7 d; p = 0.040); time HALRC patients; the choice of Scale (8/9)
undergoing LRC to oral intake not significantly urinary diversion in this group
different was main reason for this
*
Guillotreau Absence of normal 68; 38 had LRC; 30 had ORC Morbidity and mortality of LRC LRC group had lower POI incidence Laparoscopy decreases POI, Newcastle-Ottawa
et al. [23] bowel function compared with controls (11 vs 30%; p = 0.043); LRC group shortens time to fluid intake and Scale (8/9)
after POD 5 undergoing ORC had shorter times to fluid intake oral diet, and thus decreases the
(2.1 vs 4.4 d; p = 0.009), oral food time to resumption of normal
intake (3.8 vs 6.4 d; p = 0.006) and bowel function and LOS
shorter postoperative LOS (12.7 d vs
15.6 d; p = 0.033) than ORC group
*
Wang et al. [38] Not defined 54; 33 had RALRC; 21 had ORC Perioperative outcomes of RALRC RALRC group had shorter time to RALRC associated with hastened Newcastle-Ottawa
compared with controls regular diet (4 d vs 5 d; p = 0.002) return of bowel function Scale (8/9)
undergoing ORC and LOS (5 vs 8 d; p = 0.007) than
ORC group
*
Porpiglia Not defined 42; 20 had LRC; 22 had ORC Perioperative outcomes of LRC Overall POI incidence 4.2%; only LRC may be associated with early Newcastle-Ottawa
et al. [36] compared with controls time to oral intake significantly recovery of bowel function Scale (9/9)
undergoing ORC lower in the LRC group (3.3 vs 5.7 d;
p < 0.05)
*
Basillote Not defined 24; 13 had LRC; 11 had ORC Perioperative outcomes of LRC LRC group had shorter time to oral LRC associated with quicker return Newcastle-Ottawa
et al. [37] compared with controls diet (2.8 d vs 5 d; p = 0.004) and of bowel function and decreased Scale (7/9)
undergoing ORC LOS (5.1 vs 8.4 d; p = 0.0004) hospital stay
than ORC group
 EUROPEAN UROLOGY 64 (2013) 588–597 593

Maximum score of 9 points (4 for selection, 2 for comparability, and 3 for outcome). Studies considered high quality if they received 8 or 9 points; medium quality if they received 6 or 7 points, and low quality if they
ORC, respectively. Metoclopramide was associated with a

GI = gastrointestinal; HALRC = hand-assisted laparoscopic radical cystectomy; LOS = length of stay; LRC = laparoscopic radical cystectomy; NGT = nasogastric tube; ORC = open radical cystectomy; NGT = nasogastric tube;
Newcastle-Ottawa

Newcastle-Ottawa
Study appraisal
reduction in nausea and vomiting but was not significantly
Scale (8/9) associated with the incidence of POI (n = 80) [45].

Scale (9/9)
3.5.4. Standardized care pathways
Standardized care pathways use perioperative standardized
*

order sets, protocols, and/or nursing care to decrease the

Ileal conduit diversion associated

variability associated with perioperative management.

No difference in POI incidence
between ileal conduit, Indiana
with higher incidence of POI

Maffezzini and colleagues [27] applied a care pathway to

a cohort of 107 patients to determine if specific consider-
Conclusion

pouch, 3.2% for orthotopic neobladder, pouch, and neobladder

ations would reduce POI. Components of their care pathway

include no preoperative fasting, no mechanical bowel
preparation, prevention of hypovolemia/hypothermia, pain
control, early postoperative nutrition, and no NGT postop-
eratively. They concluded that decreased median times to
BM and regular diet could be achieved with the care
pathway. They observed a POI incidence of 17.7%.
and 2.0% for sexually preserving RC
Higher incidence of POI in the ileal

Chang and colleagues [2] also examined the effects of a

conduit vs ileal neobladder group

Rates for early POI were 3.4% for

pathway designed to optimize perioperative outcomes in RC

ileal conduit, 2.0% for Indiana

patients. In addition to a standardized operative approach

and postoperative laboratory order sets, patients arrived the
Results

day of surgery after completing bowel preparation at home,

with neobladder

went directly to the surgical floor postoperatively, were not

(7.4% vs 2.6%)

allowed oral intake until bowel function resumed, and did

not receive routine NGT placement. The study concluded
that their complication rates were comparatively favorable
with other institutions when using such pathway. Their
observed incidence of POI was 17%.
Indiana pouch; 62 had orthotopic following the four most widely
Intervention/comparison

orthotopic diversion compared

The value of a fast-track program to optimize periopera-

with controls undergoing ileal

281; 118 had ileal conduit; 52 had Early and late complications

tive care for RC patients was described by Pruthi and

Morbidity and mortality of

colleagues [45]. POI incidence was not included in the

results independently, and instead it was grouped with
POD = postoperative day; POI = postoperative ileus; RC = radical cystectomy; UD = urinary diversion.
conduit diversion

nausea and vomiting as ‘‘GI complications.’’ As a whole,

used UD types

these complications combined for an incidence of 12% in the

final 100 patients studied, and the fast-track program was
deemed favorable in regard to the return of bowel function.

3.6. Discussion
preserving RC with neobladder
diversion; 81 had ileal conduit

neobladder; 50 had sexually

POI has long been recognized as a significant complication

No. of patients
198; 117 had orthotopic

of any major abdominal surgery. In a recent observational

cohort of >17 000 patients undergoing colectomy in the
United States [9], ‘‘ileus, digestive complications, or both’’
occurred in 17.4% of patients. More strikingly, the POI group
diversion

accounted for an average LOS of 4.9 additional days and

overall average additional cost of $8182 compared with the
(+) received treatment; ( ) served as control.

non-POI group. Goldstein [10] found that the annual cost of

treating POI in the United States reaches up to $1.42 billion.
Definition of ileus

Patients undergoing RC are uniquely different among

Inability to resume

demographically broad and pathologically diverse abdomi-

nal surgery patients. Unlike most bowel/abdominal surgery,
oral feeding

Not defined
for >1 wk

RC deperitonealizes the pelvis for extended periods of time

to perform an adequate pelvic lymphadenectomy; patients
Table 2 (Continued )

are older and have a high incidence of comorbid conditions.

received 5 points.
Nieuwenhuijzen

This, combined with the knowledge that almost 100% of

patients undergoing this procedure have a pelvic malig-
et al. [41]

et al. [42]

nancy and are frequently smokers, further specifies the

Parekh
Study

patients we see. Other factors reinforcing the uniquely

categorical nature of RC are the extensive operative times
*
594 EUROPEAN UROLOGY 64 (2013) 588–597

Table 3 – Observational cohort with nonconcurrent comparison

Study Definition No. of patients Comparison Results Conclusion Study

of ileus appraisal
*
Kouba Not defined 102: 51 received Effect of postoperative Gum chewing may
Times to flatus (2.4 vs 2.9 d; Newcastle-Ottawa
et al. [43] gum to chew gum chewing in p < 0.0001) and to BM enhance bowel Scale (7/9)
postoperatively (+); patients following recovery and resumption
(3.2 vs 3.9 d; p < 0.001)
51 received no ORC of function after radical
shorter in (+) group than
gum ( ) controls cystectomy and urinary
diversion
Pruthi Not defined 80; 40 received Postoperative Incidence of nausea/vomiting The use of metoclopramide *Newcastle-Ottawa
et al. [45] metoclopramide (+); metoclopramide lower (2.5% vs 12.5%; reduced rates of nausea Scale (6/9)
40 did not ( ) in patients p = 0.011) in the (+) group; and vomiting and possibly
following ORC POI incidence and length of gastrointestinal
stay were not significantly complications, although
different no definite effect on POI
or resumption of bowel
function was shown
*
Abraham Not defined 34; 14 patients had Compare perioperative RALRC group had shorter time RALRC associated with Newcastle-Ottawa
et al. [44] RALRC; 20 controls outcomes in RALRC to oral intake (2.3 vs 6.1 d; reduced time to Scale (8/9)
had LRC compared with controls p = 0.012) and regular diet resumption of normal
undergoing LRC (3.7 vs 7.0 d; p = 0.011) bowel function; hospital
than LRC group stay was not decreased
by RALRC

BM = bowel movement; LRC = laparoscopic radical cystectomy; ORC = open radical cystectomy; POI = postoperative paralytic ileus; RALRC = robot-assisted
laparoscopic radical cystectomy.
(+) received treatment; ( ) served as control.
*
Maximum score of 9 points (4 for selection, 2 for comparability, and 3 for outcome). Studies were considered high quality if they received 8 or 9 points,
medium quality if they received 6 or 7 points, and low quality if they received 5 points.

often required: 4.73–9.4 h (mean: 6.11 h) [5,26,46,47] and
the presence of urine in the operative field, which has been
theorized to delay the resumption of colonic motility [48].
We conducted a systematic review of the literature
related to the incidence of POI and interventions to reduce
POI as it relates to RC patients. Our review found three
striking findings: (1) There is a paucity of studies addressing
POI following RC, (2) POI in RC populations is ill defined, and
(3) there are very limited data about interventions to
prevent/reduce POI in patients undergoing RC. This area of
research remains largely unexplored.
Our review demonstrates an incidence of POI across all
studies (9.86%) that is lower than data reported by several
other authors (12–25.4%) [2,21,27,29,45,49], and we found
that the reporting of POI is highly variable, observer
dependent, and without a standard definition. Interestingly,
the care pathways designed to optimize the return of bowel
function also all reported relatively higher rates of POI. We
speculate that this is because of improved data collection
with attention directed toward addressing POI directly. The
lower rates reflected by our review, which were remarkably
variable and as low as 2% in one study, suggest possible
underreporting of POI by many published studies.
Throughout our review we observed that the definition
of POI is not given or is inconsistent. When stated, the
definition varied considerably, in many cases grouped with
more general GI complications and bearing a confusing
alternative nomenclature (eg, subileus). However, in most
cases, it is not defined at all. Given that POI is generally a
clinical diagnosis, it is critical to clearly report the definition
being used because it may vary significantly. Alternatively,
an improved reporting strategy may be used routinely to
capture secondary measures of POI including time to flatus,
time to first BM, time to toleration of first oral intake, and LOS.
These outcomes have less heterogeneous definitions and
would be more amenable to the application of statistical
techniques in the future such as in a meta-analysis.
We also found that most of the information on
prophylaxis, prevention, and treatment of POI in RC
populations comes from observational cohort studies, with
scarce data coming from experimental controlled studies.
Studies by Roth and colleagues [34] and by Nix and
colleagues [33] do shed light on the benefits of readaptation
of the peritoneum and robotic techniques, respectively,
with regard to hastened bowel recovery. Additionally,
Lightfoot and colleagues [35] conducted a RCT demonstrat-
ing that erythromycin did not hasten the return of bowel
function in RC patients. However, that study had a sample
size of 22 patients and lacked substantial power to detect a
small difference in treatment effect.
A recently completed large RCT aimed to study the
effectiveness of alvimopan versus placebo among a RC
population [50]. As noted earlier, alvimopan is a peripher-
ally acting m-opioid receptor antagonist, which because of
its limited ability to cross the blood–brain barrier, is
reported to avert the undesirable intestinal side effects of
opioid agonists without affecting analgesia. The results of
this study will provide invaluable information regarding
this potential preventive option.
Robotic surgery has recently changed the face of
emerging literature. In a 2010 prospective cohort, Ng and
colleagues [25] demonstrated that when compared with an
open group, robotic RC had a significantly lower 30-d
complication rate. Our review identified several studies
 EUROPEAN UROLOGY 64 (2013) 588–597
comparing a robotic approach with both a laparoscopic and
open approach. All of these showed a trend toward a
hastened return of bowel function in the robotic groups, but
none were RCTs. A multi-institutional prospective random-
ized trial to evaluate open versus robotic RC is underway,
and the results will be highly informative [51].
Identifying risk factors for POI is also important for
counseling and targeting perioperative management. We
reviewed the available literature addressing risk factors for
POI. Specifically, increasing age and BMI, ethnic minority,
increasing estimated blood loss/transfusion requirement,
and the presence of a major complication were all
associated with POI in RC patients. This information is
the cumulative knowledge from only five observational
cohort studies. As hypothesized by Svatek and colleagues
[29], BMI and age may be associated with increasing POI
because of increased times to ambulation and more
extensive/difficult bowel manipulation. They also noted
increased overall rates of complications in these groups,
consistent with the findings of Chang and colleagues [2]
that the development of a major complication is an
independent risk factor for POI. Conversely, we did not
find any evidence that POI independently predicts occur-
rence of other complications. The available literature
regarding age and POI is conflicting, and addressing the
association of age with POI is challenging because it is
possible that elderly patients, especially those with cogni-
tive impairment, do not reliably report markers of bowel
function such as flatus and thus compound the variability of
such measurements. Standardization in data collection and
reporting of POI and secondary measures is imperative as
we move forward to allow for accurate comparisons among
populations and interventions.
At this time, it would be difficult to give solid
recommendations on POI prevention given the paucity of
data. It seems that gum chewing is a simple measure that
could potentially help prevent POI with minimal risk. Based
on the available data, it also appears that omission of a NGT
may be beneficial in that it can lead to decreased LOS and
not result in an increased risk of POI. Bowel preparation also
seems to be unnecessary and may appear to be detrimental
in some of these cases. It also appears that, when possible,
readaptation of the peritoneum may hasten bowel recovery.
However, it is important to acknowledge that, given the
nonrandomized nature of these studies and the lack of
standardized pathways used, potential confounders exist,
particularly for the control cohorts that may have had a
significant impact on the findings reported. Standardization
of perioperative management via care pathways has the
potential to decrease adverse events, improve care, and
decrease health care expense. As far as robotic RC versus
ORC, it would be prudent to wait for the results of the multi-
institutional prospective RTC before making any recom-
mendations.
This review certainly has limitations. Although we
designed our search criteria to be very flexible and far
reaching, we acknowledge that we may have missed
important factors that might influence POI. Our assessment
of the methodological quality of the studies is limited by the
595
somewhat subjective nature of the current validated tools.
Although inadequate methodology and poor reporting
quality are usually coupled with bias and thus provide an
indirect measure of it, there can certainly be instances of
studies adhering to the highest of reporting standards yet
they have fundamental flaws and biases. Finally, essentially
all of these series come from single-institution studies in
academic centers with relatively high individual surgeon
volume, which might limit the interpretation and gener-
alizability of their findings.
To better understand POI, so that we might curtail the
impact it has on RC patients, future studies are needed
specifically targeting RC populations. It is critical to revisit
those interventions that this review has identified as
beneficial in curtailing POI by conducting prospective
controlled trials specifically for RC patients.
4. Conclusions
The incidence and definition of POI after RC is highly
variable. An improved reporting strategy is needed to
identify true incidence and risk factors and, most important,
to guide future research for both potential preventive and
therapeutic interventions.
Author contributions: Robert S. Svatek had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Svatek, Lawrence.
Acquisition of data: Ramirez, McIntosh, Strehlow.
Analysis and interpretation of data: Svatek, Lawrence, Parekh, Ramirez,
McIntosh, Strehlow.
Drafting of the manuscript: Svatek, Lawrence, Ramirez, McIntosh,
Strehlow.
Critical revision of the manuscript for important intellectual content: Svatek,
Lawrence, Parekh, Ramirez, McIntosh, Strehlow.
Statistical analysis: Svatek.
Obtaining funding: None.
Administrative, technical, or material support: Svatek.
Supervision: Svatek.
Other (specify): None.
Financial disclosures: Robert S. Svatek certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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