University of Southern California Dissertations and Theses

Enhanced recovery pathway following radical cystectomy

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Enhanced recovery pathway following radical cystectomy

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1

Enhanced
Recovery
Pathway
Following
Radical
Cystectomy

From
the
Institute
of
Urology,
USC/Norris
Comprehensive
Cancer
Center,
Los
Angeles,

California

Authors:

1)
Hooman
Djaladat,
M.D.

Assistant
Professor
of
Urology

Norris
Comprehensive
Cancer
Center

USC
Institute
of
Urology

Los
Angeles,
CA

2)
Siamak
Daneshmand,
M.D.

Associate
Professor
of
Urology

Norris
Comprehensive
Cancer
Center

USC
Institute
of
Urology

Los
Angeles,
CA

Corresponding
Author:

Siamak
Daneshmand,
MD

Department
of
Urology

1441
Eastlake
Avenue,
Suite
7416

Los
Angeles,
CA
90089

P:
(323)
865-‐3716

F:
(323)
865-‐0120

daneshma@usc.edu

Word
count
abstract:
122

Word
count
text:

2046

Number
of
tables:

1

Number
of
references:

23

Source
of
Funding:

None

2

Degree
Conferral
date:
August
2014

Table
of
Contents:

Abstract

page
3

Introduction

page
4

ERAS
protocol

page
5

USC
ERAS
protocol

page
7

USC
ERAS
result

page
9

Conclusion

page
10

Conflict
of
interest

page
10

Key
points

page
10

References

page
11

Table
1

page
14

3

Abstract

Purpose
of
review:
To
evaluate
peri-‐operative
enhanced
recovery
protocols
for

patients
undergoing
radical
cystectomy
and
urinary
diversion
and
describe
our

unique
protocol.

Recent
findings:
Radical
cystectomy
is
a
morbid
procedure
with
rather
long

hospital
stay
and
complication
rates.
The
main
reason
for
lengthy
hospital
stay
is

bowel
complication
including
paralytic
ileus.
Different
perioperative
care
plans
have

been
recommended
to
decrease
hospital
stay
and
complication
rate.
Most
of
this

recovery
plans
focus
on
enhancing
gastrointestinal
function
recovery,
pain

management
and
early
mobility.

Summary:
Enhanced
recovery
after
surgery
protocol
includes
pre,
intra
and
post-‐
operative
evidence-‐based
modifications
for
improving
perioperative
care
of

cystectomy
patients.
Significant
shortening
of
hospital
stay
without
increasing
early

complication
or
re-‐admission
rate
could
be
achieved
safely
in
most
of
the
patients.

Keywords
(MeSH)

Radical
cystectomy,
enhanced
recovery,
protocol,
post-‐operative
pathway

4

Introduction:

Enhanced
recovery
after
surgery
(ERAS)
protocols
are
evidence-‐based
multimodal

care
pathways
that
aim
to
provide
optimal
perioperative
care
for
patients

undergoing
complex
surgeries.
The
goal
of
these
protocols
is
to
minimize

perioperative
stress
and
promote
acute
recovery,
demonstrated
by
significant

reduction
in
hospital
stay
with
no
adverse
effects
on
complication
or
re-‐admission

rates.
Enhanced
recovery
protocols
are
first
introduced
in
patients
undergoing

colectomy
and
include
a
considerable
number
of
pre-‐operative,
intraoperative
and

post-‐operative
changes
in
management
compared
to
standard
protocols,
including

reduced
pre-‐operative
fasting
to
early
post-‐operative
feeding
[1].
Results

demonstrated
reduced
post-‐operative
complications
and
faster
recovery
[2].
There

is
scant
data
on
enhanced
recovery
protocols
in
complex
urology
surgeries.
Radical

cystectomy
and
urinary
diversion
remain
one
of
the
most
complex
and
morbid

procedures
in
urology
with
high
complication
rates
and
hospital
stay
[3].
There
has

been
a
significant
lag
in
the
adoption
of
such
protocols
in
urologic
surgery
which
is

most
likely
multi-‐factorial
and
may
include
the
belief
that
urinary
diversion
is
a

more
complex
operation
than
colorectal
surgeries
with
subsequent
higher
gastro-‐
intestinal
complications,
persistence
of
surgical
dogma,
or
the
fact
that

implementation
of
such
protocols
requires
considerable
effort.
The
main
reasons
for

prolonged
hospital
stay
following
cystectomy
remain
gastrointestinal
complications,

mostly
paralytic
ileus
[3].
Improvement
in
surgical
technique,
anesthesia
and

perioperative
care
has
resulted
in
reduced
morbidity
and
length
of
stay
(LOS)
after

cystectomy.
Previous
investigators
have
described
standardized
peri-‐operative
care

for
patients
undergoing
radical
cystectomy,
with
a
reduction
in
the
mean
hospital

stay.
[4].
Herein,
we
discuss
the
current
literature
on
the
topic
and
describe
our

enhanced
recovery
protocol
for
patients
undergoing
radical
cystectomy
and
urinary

diversion
using
our
institutional
evidence-‐based
model.

5

ERAS
protocols

Improvements
in
surgical
technique,
anesthesia
and
perioperative
care
has
recently

resulted
in
reduced
morbidity
and
LOS
after
cystectomy
although
the
mean
hospital

stay
at
most
centers
remains
high
at
10-‐11
days
[5]*.
Pruthi
et
al.
pioneered
to

describe
a
perioperative
care
plan
on
40
patients
underwent
cystectomy
for
bladder

cancer
with
decreased
mean
hospital
stay
of
5.1
days.
[4].
Arumainayagam
et
al.

reported
their
experience
with
enhanced
recovery
protocol
(ERP)
in
patients
with

bladder
cancer
who
underwent
cystectomy
in
the
UK
[3].
The
three
most
important

components
of
their
protocol
were
no
bowel
preparation,
early
enteral
feeding
and

mobilization.
Median
LOS
following
cystectomy
was
13
(11-‐17)
days
in
cases
with

ERP
vs.
17
(15-‐23)
days
in
controls
(p
<
0.001).
The
significant
difference
between

US
and
UK
healthcare
system
model
should
be
taken
into
account
when
interpreting

these
numbers.
In
2010,
Pruthi
et
al.
updated
their
initial
experience
using
their

perioperative
care
plan
on
100
patients
with
focus
on
early
NG
tube
removal,
earlier

feeding
and
use
of
prokinetic
agents.
They
demonstrated
the
beneficial
effect
of
non-‐
narcotic
analgesic
pain
management
and
gum
chewing
with
no
detrimental
effect
of

not
having
an
NG
tube
after
the
surgery.
They
still
used
bowel
preparation
prior
to

surgery
with
advancement
to
regular
diet
by
postop
day
(POD)
4.
They
reported
on

mean
time
to
bowel
movement
of
2.9
days
and
mean
LOS
of
5
days
[6].
Vanderbilt

has
also
described
their
experience
with
a
collaborative
care
pathway
in
a
group
of

304
patients
undergoing
radical
cystectomy
and
urinary
diversion
resulting
in

discharge
at
POD
6-‐8
in
74%
of
patients.
The
pathway
included
mechanical
bowel

preparation,
full
liquid
diet
after
bowel
function
return
and
home
health
support

after
discharge.
Delayed
discharge
is
independently
correlated
with
post-‐operative

ileus
(most
common),
minor
or
major
complication
and
blood
transfusion
[7].

Maffezzini
et
al.
also
reported
on
a
multimodal
care
plan
to
enhance
recovery
in
71

patients
undergoing
radical
cystectomy.
The
pathway
included
preoperative
bowel

preparation,
epidural
catheter,
jejunostomy
cannula
and
early
NG
tube
removal.

6

Median
time
to
return
of
bowel
function
is
2
days
and
median
LOS
is
15
days
[8].

Mechanical
bowel
preparation
has
been
traditionally
recommended
for
patients

undergoing
bowel
resection
but
can
cause
dehydration
and
electrolyte
imbalances.

A
meta-‐analysis
performed
to
investigate
the
effect
of
bowel
preparation
in

reducing
the
incidence
of
postoperative
complications
in
patients
undergoing

elective
colorectal
procedures
showed
no
differences
in
rate
of
mortality,
re-‐
operation,
peritonitis
and
wound
infection
[9].
Preoperative
carbohydrate
loading

has
been
shown
to
play
an
important
role
in
decreasing
hospital
stay
and
recovery

after
colonic
surgery
in
a
randomized
controlled
trial
[10]
Nasogastric

decompression
has
traditionally
been
used
following
cystectomy
to
decompress
the

stomach,
prevent
emesis
and
aspiration
and
protect
the
bowel
anastomosis.
Donat

and
colleagues
described
an
overnight-‐only
NG
tube
with
use
of
metoclopramide

demonstrating
the
benefits
of
early
return
of
bowel
function
and
reduced

pulmonary
complications.
[11].
These
benefits
have
been
confirmed
by
numerous

other
studies
[5][12]
[13]
[9]
[14]
[15],
yet
the
use
of
NG
tubes
following
cystectomy

and
diversion
remains
very
high.

Prokinetics
like
metoclopramide
have
been
shown
to
significantly
reduce
rate
of

postoperative
nausea
and
vomiting
with
an
early
tolerance
of
solid
foods
[12].

Postoperative
ileus
stands
out
as
one
of
the
most
common
causes
of
increased
LOS

after
cystectomy
[8][16].
Opening
the
peritoneum,
bowel
manipulation,
resection

and
anastomosis
and
hypo
or
hypervolemia
may
all
contribute
to
peristalsis

impairment
[8][15].
Opioid
receptors
are
distributed
throughout
the

gastrointestinal
(GI)
tract,
indicating
that
endogenous
and
exogenous
opiates
can

modulate
GI
motor
and
secretory
functions.
Most
opiates
that
have
a
µ
receptor

activity
inhibit
gastric
motility
and
delay
emptying
as
well
[17].
Alvimopan,
a
µ-‐
opioid
receptor
antagonist
has
been
shown
in
multiple
randomized
trials
to

accelerate
gastrointestinal
activity
after
bowel
resection.
In
patients
undergoing

radical
cystectomy,
it
has
been
shown
to
significantly
decrease
time
to
bowel

activity
and
hospital
stay
[18].
Recent
results
of
a
phase
IV
study
on
the
decrease
in

LOS
with
the
use
of
Alvimopan
is
currently
in
press.
Accurate
fluid
delivery

7

perioperatively
can
prevent
both
dehydration
and
hypervolemia,
reducing
surgical

complications
and
shortening
LOS
[19].
Ketorolac,
a
non-‐narcotic
analgesic,
has

been
shown
not
only
to
reduce
narcotic
demand,
but
also
hasten
the
return
of
bowel

myoelectrical
activity
after
laparotomy
[5][20].
Post-‐operative
gum
chewing
has

been
shown
to
stimulate
oral-‐gastric
reflexes
and
bowel
motility
in
both
colorectal

and
cystectomy
literature
[5][21,
22].
Neostigmine,
an
acetyl
cholinesterase

inhibitor,
has
also
been
shown
to
be
associated
with
decreased
time
to
flatus
and

bowel
movement
following
bowel
resection
[23]*.

USC
ERAS
protocol:

This
includes
pre,
intra
and
post
cystectomy
care
modifications.

Pre-‐operative:

Given
the
evidence
against
the
use
of
bowel
preparation,
and
the
potential
for

increasing
complications,
we
have
omitted
all
bowel
preparation
prior
to
surgery

unless
there
is
a
preoperative
plan
for
using
the
colon
for
continent
cutaneous

diversion.
A
high-‐protein
high-‐carbohydrate
liquid
drink
is
recommended
for
few

days
prior
to
surgery,
without
any
other
special
diet
recommendation.
The

preoperative
visit
and
an
educational
class
help
to
detect
any
psychosocial
barriers

that
might
interfere
with
early
recovery
and
discharge.
It
also
improves
patient

compliance
with
ERAS
and
provides
better
understanding
of
meeting
postoperative

milestones
prior
to
discharge.
Alvimopan,
a
µ-‐opioid
receptor
antagonist,
is
given
in

the
pre-‐operative
holding
area
30-‐60
minutes
prior
to
the
operation.
No
epidural

analgesia
is
used
in
order
minimize
the
use
of
narcotics.

Intra-‐operative:

In
general,
cystectomy,
extended
pelvic
lymph
node
dissection
and
urinary

diversion
are
performed
through
an
infraumbilical
incision.

Blood
loss
and
surgical

time
are
kept
to
a
minimum.
Intraoperative
fluid
intake
is
maintained
by
warm

ringer
lactate
solution
plus
albumin
bolus,
if
needed.
Fluid
intake
is
minimized
while

the
ureters
are
clipped.
Intravenous
acetaminophen
acetate
is
started

8

intraoperatively
and
narcotic
use
is
kept
to
a
minimum.
The
patient
is
then

transferred
to
the
ward
unless
there
is
any
indication
for
admission
to
intensive

care
unit.

Post-‐operative:

NG
tube
(if
used)
is
removed
at
the
conclusion
of
surgery.
All
patients
are
monitored

on
telemetry
while
they
receive
neostigmine.

a)
Gastrointestinal
recovery

Alvimopan
is
continued
postoperatively.
Neostigmine
is
also
administered
to

facilitate
the
regaining
of
gastrointestinal
tract
motility.
Both
neostigmine
and

alvimopan
are
discontinued
once
the
patient
has
a
bowel
movement.
A
magnesium-‐
based
lactulose
or
bisacodyl
(suppository)
is
started
on
POD
1
and
continued
daily

until
bowel
movement.
Prophylaxis
for
stress
ulcer
(proton
pump
inhibitor
and
H2

receptor
blocker)
and
nausea
and
vomiting
(ondansetron
and/or
metoclopramide)

is
administered
regularly.
Patients
are
encouraged
to
ambulate
starting
POD
1.
Sips

of
liquids
(including
high-‐carbohydrate
high-‐protein
fluids)
are
started
early
on
the

day
of
surgery
if
tolerated.
On
POD
1,
a
clear
liquid
diet
is
started
and
gradually

increased.
Regular
diet
is
started
on
POD
2
if
the
patient
has
no
nausea,
vomiting
or

abdominal
distention
regardless
of
gas
passage
or
bowel
movement.
More
recently

we
have
implemented
stating
regular
diet
(tailored
for
post-‐operative
surgical

patients)
on
POD
1.
If
the
patient
is
not
tolerating
oral
food
by
POD
6
and
there
is
no

bowel
activity,
the
parenteral
nutrition
is
considered.

b)
Pain
management

Intravenous
ketorolac
tromethamine
and
acetaminophen
acetate
are
the
mainstay

of
early
postoperative
pain
management,
if
not
contraindicated.
Para-‐incisional
sub-‐
fascial
catheters
with
constant
local
anesthetic
(0.2%
Ropivacaine)
release
are
also

used
for
local
pain
control.
Rapid-‐onset
opioid
is
reserved
for
breakthrough
pain.

Oral
painkillers
are
started
on
POD
1
and
most
of
the
patients
are
transitioned
to

oral
analgesics
by
POD
3.

9

c)
Discharge
and
post-‐op
care

Discharge
orders
are
written
when
patient
meets
the
following
criteria:
(1)

adequate
pain
control
with
oral
medications
(2)
adequate
mobility
and

catheter/stoma
care
(3)
normal
laboratory
results
(4)
adequate
oral
intake
(≥
1

liter/day)
(5)
having
bowel
movement.
In
addition,
prophylactic
antibiotic
is
started

and
continued
for
three
weeks
or
until
catheter/stent
removal.
Starting
from
patient

25,
alkalinization
(with
oral
sodium
bicarbonate)
was
also
added
to
the
protocol
if

discharge
bicarbonate
was
low
(<
24
mmol/L).
Patients
are
scheduled
to
return
to

clinic
one
week
after
discharge
for
the
first
postoperative
visit
and
laboratory
check.

In
order
to
ensure
adequate
hydration
during
early
post-‐discharge
period,
patients

are
arranged
to
receive
intravenous
fluid
therapy
at
home
through
a
peripheral
IV

as
well
as
follow-‐up
phone
calls
from
the
nursing
team
every
other
day.

USC
ERAS
result:

In
our
study,
68%
of
the
patients
underwent
continent
urinary
diversion.
The

median
hospital
stay
in
110
consecutive
patients
undergoing
open
radical

cystectomy
and
urinary
diversion
on
our
ERAS
protocol
was
4
days.
This
is
a

significant
reduction
from
the
8-‐day
LOS
in
a
matched
pair
analysis
using
484

patients
on
USC-‐STAR
trial
(Studer
versus
T
pouch
diversion
after
cystectomy,

2002-‐2009),
(p
<
0.0001)
(Table
1).
The
most
likely
significant
contributing
factors

are
using
no
bowel
prep,
decreasing
the
narcotic
use,
usage
of
alvimopan,

cholinergic
drugs,
prokinetic
agents
and
early
feeding.
Other
factors
such
as

suppository
use
and
nutritional
support
with
high
carbohydrate
diet
may
have
a

minor
role
in
our
ERAS
protocol.
Minimizing
the
incision
by
using
an
infra-‐umbilical

approach
may
also
lead
to
less
pain
and
better
control
by
local
anesthetics
through

subfascial
catheters.
Surgical
experience
with
expedited
surgery
and
less
blood
loss

most
likely
plays
an
integral
role
in
accelerated
postoperative
recovery.
Median
OR

time
in
our
study
is
352
minutes
and
median
estimated
blood
loss
(EBL)
is
400
mL.

Median
time
to
flatus
and/or
bowel
movement
is
2
days.
An
NG
tube
was
reinserted

in
5
patients
(4%)
secondary
to
persistent
ileus
and/or
vomiting,
with
no
incidence

10

of
anastomotic
leak
or
early
bowel
obstruction.
30-‐day
complication
and
re-‐
admission
rate
in
the
cohort
of
110
ERAS
patients
is
61%
and
21%
that
is
not

statistically
different
from
the
STAR
trial
cohort
(65%
and
22%
respectively,
p
>

0.05).

Conclusion:

Our
ERAS
protocol
for
radical
cystectomy
includes
evidence-‐based
pre,
intra
and

post-‐operative
modifications
that
decrease
hospital
stay.
The
protocol
is
not
a

substitute
for
meticulous
surgery,
nor
is
it
a
means
of
imposing
patients
to
be

discharged
sooner
to
receive
their
postoperative
care
by
home
health
nurses.
It
is
an

evidence-‐based
protocol
designed
to
enhance
the
patients’
experience
and
recovery

from
cystectomy.
The
protocol
is
feasible
and
safe
for
essentially
all
patients
and
is

associated
with
significant
shortening
of
hospital
stay
without
increasing
re-‐
admission
rate.

Conflicts
of
interest:
None

Key
points:

• Enhanced
recovery
protocol
for
patients
with
radical
cystectomy
includes
pre,
intra

and
post-‐operative
modifications
to
standard
care.

• The
highlights
of
protocol
are
carbohydrate
loading,
no
bowel
prep,
no
post-‐op
NG

tube,
focus
on
non-‐narcotic
pain
management,
peripheral
μ
receptor
opioid

antagonist,
use
of
neostigmine
and
early
feeding.

• The
protocol
is
feasible
and
safe
and
is
associated
with
significant
shortening
of

hospital
stay
without
increasing
complication
or
re-‐admission
rates.

11

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Zhong
Y,
Xue
Z,
Jin
L,
Zhan
S
et
al:

Enhanced
Recovery
After
Surgery
(ERAS)
program
attenuates
stress
and

accelerates
recovery
in
patients
after
radical
resection
for
colorectal
cancer:
a

prospective
randomized
controlled
trial.
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J
Surg
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36(2):407-‐414.

* Ref
23:
Level
I
evidence
as
it
discusses
RCT
in
ERAS
for
colorectal
patients.

* Ref
5:
This
article
shows
the
importance
of
leapfrog
volume
effect
on
the
risk
of

mortality
and
complications
after
radical
cystectomy.

14

Table.1

Comparison
between
ERAS
and
STAR
(Studer
vs.
T
pouch
trial)
cohorts

NS:
Non
significant

Abstract (if available)

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Asset Metadata

Creator Djaladat, Hooman (author)

Core Title Enhanced recovery pathway following radical cystectomy

School Keck School of Medicine

Degree Master of Science

Degree Program Clinical, Biomedical and Translational Investigations

Publication Date 08/08/2014

Defense Date 08/07/2014

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag enhanced recovery,OAI-PMH Harvest,post‐operative pathway,protocol,radical cystectomy

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Lieskovsky, Gary (committee chair), Azen, Stanley P. (committee member), Boyd, Stuart (committee member)

Creator Email djaladat@usc.edu,hoomanj@yahoo.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-457411

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Legacy Identifier etd-DjaladatHo-2789.pdf

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