Full text of DOI:10.1177/0148607100024006351

in
Tube
Children
on
Effect
with Cancer: The
of
Feeding
Nasogastric
Two
Different Formulas
Weight, BodyComposition,
and SerumProtein
Concentrations
Eline den
J.
Martin A. van
Robert J.
’t
Broeder, MSc*;
Tolboom, PhD*;
PhD*;
Hof, PhD†;
Lippens,
Sengers,
Jules J. M.
Robert C. A.
Zandrie
Anneke M. J. van den
A. van
PhD*;
Berg‡;
Nicole B. M. van
and
Houdt‡;
Hofman, IR§;
Staveren,
PhD∥
Wija
and
From the
Statistics,
University
Center,
University
of *Pediatrics
Wageningen;
‡Dietetics,
Hospital
†Department of Medical
Epidemiology, Wageningen
Department
Research,
University
Nijmegen;
of Nijmegen;
The
and
Nutrition and
Netherlands
of Human
§Numico
∥Division
<
of mean
5.2% to
Treatment
of
administration
cancer
of
cachexia
amounts of
ABSTRACT.
involves
.05)
and 10
in the
in
increase,
25.5%;
p
(range
nificantly
Background:
the
the first
4
weeks of intervention. Between
during
variables continued to
weeks,
4
adequate
partly
increase
in
ofthis
wasto assess the tolerance and
volumes of tube
Theaim
energy.
study
significantly
a
of two
one with
energy-enriched group, resulting
adequate repletion,
efficacy
equal
feeding,
The
andonewith
a
contrast to the standard formula
concentration of
returned to
standard
kcal/mL)
(1
(1.5
high energydensity
group.
the
of
serum
at initiation oftube
low
intensive
Nutritional status was assessed
treatment. Methods:
kcal/mL),
during
phase
feeding,
4 weeks
to with no
Conclusions: The
groups.
proteins,
in
2
27 children with
the normal
within
range
arm differences betweenthe two
weekly,
significant
a
solid
tumor,
measuring
and
teins. Tolerance was assessed
energy-
nutri-
the
by
biceps
weight, height, midupper
and serum
in
enriched formula was more effective
circumference,
skinfold,
triceps
pro-
improving
of children with cancer the intensive
status
the occurrence of
tional
by
recording
during
than the standard formula.
and
administered volume
as
the
a
of treatment
Intensive,
formula
vomiting
by
expressing
required
phase
protocolized
of the
well
intake in the
volume. Results: Both formulas
administration of an
percentage
were
energy-enriched
to
a
should therefore be initiated as soon as one ofthe criteria for
tolerated,
equally
leading
energy-enriched
anthropometric
significantly higher
formula In both
tube
Parenteral
and
initiation of
Enteral Nutrition
is met.
energy
formula
of
group.
variables increased
Journal
2000)
feeding
24:351-360,
all
groups,
sig-
Cachexia is common in
with cancer and is
children
reducedoral
the oral
of
a
child with
the
increase
is
ment
intake
or
cancer,
energy
caused
a
relative
or
of
mainly
to energyexpenditure.
the intensive
by
intake,
energy
present
incapable
reversing
develop-
preventing
It canbe
at
of
treat-
and total
of cachexia
the intensive
diagnosis
during
phase
treatment.l-7
anticancer
characterized
ment.1,2,lS
teral nutrition
develop during
This metabolic
tube
Nasogastric
feeding
oftenused
paren-
clin-
complex
syndromeis
therefore are
andhave
(TPN)
a
loss of
weight,
ically
involuntary
by
progressive,
shown to
tional status ofchildren
or
the nutri-
the inten-
maintain
effectively
improve
with cancer
and
an accelerated breakdown of
adipose
through
during
in visceral
decrease
muscle
and
a
tissue,
protein
of
by
sive of treatment. 2,12,16-21
However,
phase
nasogastric
The
a
concentrations. 4,6-8
include
implications
negative
has
in
and tol-
which
shown to be
acceptable
feeding,
to
reduced tolerance
this condition
therapy,
erated
children with
after
cancer soon
is
more
by
diagnosis,
an increased
immune
an
suscepti-
and de-
response,
a
impaired
a
more
considered
and
safer,
simpler,
physiologic,
to
infections,
growth
bility
velopment,
mance,
delayed
allows
economicintervention
which
for
than
TPN. 2,10,21-23
amore
method,
of
reduced state
and
a
a
perfor-
outcwomeel.l-1,b2e,i5,n9g, 10
and
normal life
style
as
activity,
play
Theneed
clinical
or reversal
and
poorer
as
the
func-
tract
Therefore,
tion is
long
gastrointestinal
with
in children
of cachexia
for
prevention
is
to
feeding
preferred
adequate, nasogastric
metabolic
ofthe
involves the correction
which
cancer,
TPN. 2,10,23
child’s
and
is therefore
the
energy
increasing
of
derangements
with
are available
intake of children with
on the
formulas,
Manytube-feeding
varying composi-
and has
the utmost
intake,
been
litiermaptuorret.a1n,c4,e5,11-14
on the
tion and
marketto
cancer.24
of
density,
energy
energy
the
in
emphasized repeatedly
Intensive nutrition
improve
Their
to
alone, aiming
counseling
efficacy mainly depends
feasibility
the
Previous
meeting
patient’s energy requirements.
have shown that these
studies
energy
requirements
low
often are not met because of
of
infusion rates
during
due to
Eline den
of
Pediatrics,
Correspondence:
Broeder, MSc, Department
St
the initial days
medical
feeding, feeding interruptions
and inadvertent
KOC
Box
PO
Radboud,
921,
9101,
University
Hospital Nijmegen,
6500HBNijmegen,
extubation,
gas-
procedures
TheNetherlands.
sentto
mailmaybe
Electronic
trointestinal
and
e.denbroeder@ckskg.azn.nl
intolerance,
suboptimal prescribed
351
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352
19, 25-27
mon- were
to receive
of
chemother-
were eli-
thatcareful
was
It
expected
cycles
the
suggested
cytotoxic
energy
itoring
might
goals.
or
oftube
administration
and
feeding apy
radiotherapy during
study period,
protocolized
and
for the
in
Patientswereincluded the
of
incidence
diminish the
gible
study.
study
complications
tube feed- whenat least oneofthe
was met
and
of
inclusion criteria
or thatthe volume
increase
intake
be
energy
simply
for feed- when none of the exclusion criteria were
to
increased
applicable.
compensate
ing may
The
a
the volume
inclusion criteria were as follows:
(1)
present
However, increasing
ing interruptions.~~°25
to
or
was
volume state ofmalnutrition at
that failed
infuse this
failure to
lead to
a
diagnosis
may
because of
the
persistent
within
>5%
1
not
after
to
loss
intolerance. 21,21
(2)
week;
Increasing
the other
improve
that was
weight
at
<80%
expected
gastrointestinal
fromthe
formula
on
the
of
weight
diag-
of
total
diagnosis
may,
energy density
thatwas
the
and
oral
(3)
intake
intake without
or
increase
nosis
;
increasing
energy
hand,
volume.
energy
below).
(see
study
energy requirements
However,
hyperosmolarity
hypercaloricity
who
combination
were
due to
Excluded from the
were
with
side
lead to
also
effects,
patients
may
delayed gastric emptying,
gastrointestinal
and,
in
to
a
to receive corticosteroids
for >7
expected
subsequently,
an
with
of
in the volume and amount
reduction
chemotherapy
days, patients
energy
received
who
vary.24e,2n6e,r2gy
who
of >3000
even
data on this issue
kcal/d,
requirement
patients
though
provided,
This
ofshort-
nutrition
at
wasinitiated to assess the effect
diagnosis, relapsed patients
therapy
study
had
in
and
due to
and
volumesof
administration of
weeks)
the
who
chemother-
(10
weeks)
(4
before,
feeding
problems
participated
study
patients
long-term
available tube-feed- hadbeen intolerant to tube
two
equal
commercially
within
2
one with
a
standard
andone
on the nutri-
weeks
was
(1 kcal/mL)
formulas,
gastrointestinal
apy-related
ing
with
a
of initiation of tube
1
(1.5
kcal/mL),
high energy density
feeding. Only
patient
tional status ofchildren with
a
solid tumor
the excluded on the basis ofthe last criterion. His
during
gastro-
intensive
Five
standard
oftreatment.
with
intestinal tract was
chemother-
phase
severely damaged by
to the
and
andhe had
to resort to TPN.
(methotrexate),
energy-dense
apy
In
aspects,
respect
were
29
in
were included the
studied:
but
total,
formulas,
patients
in
the
study,
27
1. The effect on
the overall nutri-
couldbe used
of
lost for
the
2
because
weight, reflecting
only
analysis
data,
status.
withdrew and
tional
were
Committee of
the
The
patients
follow-up.
on
reflected in
changes
Medical Ethics
2. Theeffect
bodycomposition,
Hospital
University
in skinfold
circumfer-
study. Awritteninformed con-
thicknesses,
midupperarm
Nijmegen approved
sent was obtained
ence
and armmuscle area
from
the
of each
(AMA).
(MUAC),
parents
patient
the
3. The effect on several serum
nutritional status.
reflecting
entering
study.
proteins,
4. The occurrence of
and the volume admin-
vomiting
of the volume
Tube
Feeding
Regimen
istered as
a
required,
percentage
the tolerance ofthe formulas.
The total
kilocalories
the
in
ofeach
daily
reflecting
energy requirement
child,
24
5. Protocol adherence and dose reductions.
was calculated
performula 29,30 :
hours,
using
weekly
X
Basal metabolic rate
following
+
factor
X
X
Illness
factor -
Growthfactor
1)
(Activity
MATERIALS AND METHODS
factor.
Absorption
Study
Design
Basal metabolic rate
to
(kcal/24
determined
h),
according
age,
the Schofield
and
was
sex,
formulas. 3- The child’s
weight,
using
was
a
double-
The
blind
randomized,
study
prospective,
was
described
physical activity
trial
a
formula
kcal/mL,
slightly
clinical
involving
tube-feeding
the
and
converted
into an
to
factor
by
parents
activity
of
&dquo;standard&dquo;
(1.0
energy density
from 1.2 to
data from
the
ranging
1.7,
according
Nutrison Pediatric
Numico
and formula of
Nutrison Pediatric En-
of both formulas was
Standard;
N.V.,
&dquo;high&dquo;
adapted
Health
of
and Jacobs et al. 33
Department
(London),32
The
a
Netherlands)
Zoetermeer,
The
illness and
factors of
children in
factor,
the
absorption
(1.5
The
kcal/mL,
energy density
this
were
considered to be 1.2 The
study
growth
Numico).
ergy ;
composition
used to correct for
was
determined
(WFH)
loss,
weight
by
by
and
in
differed
that the
of
more
energy-enriched
equal
only
the child’s
for
dividing
target weight
height
formula
1.5 times
nutrient,
provided
every
formula
group
the actual weight. Target WFHwas
determined from
Fifteen
including protein.
patients per
child’s
available from
the
data
the
At
preillness growth
health services and the school
werecalculatedto detect
a
difference in nutrition effect
municipal
physician.
of6%withan
a
.05 and
a
of
an
80%,
power
assuming
in
to 0.5
as
before
of the
time,
every point
years
percentage
up
diagnosis,
SD of6%.21
in
formulas were randomized
Thirty
pairs
was
standard
weight
WFH
expressed
and
were
a
(block
randomization),
patients
assigned
and
to
reference
(P50)
according
age-
sex-specific
formula number in the order of inclusion into the
The
all preillness WFH
meanof
percentiles.34
percent-
for the actual
after
was initiated.
The
which tube
started at the initiation of tube
study,
study period
and ended after 10 weeks.
feeding
the P50 of
was used as
ages
by
weight
multiplied
at
feeding
height
diagnosis
target weight.
(week
0)
The volume of tube
to be
was
administered
100% of the total
the
feeding
child with
each
set to
provide
daily
study
Patients
However,
energy requirement.
during
1
18
it was unknown whether
All children between
and
of
the child received
formula.
years
age,
period,
newly
with
or the
cancer at the
the standard
Therefore,
was calculated under the
diagnosed
Nijmegen
University Hospital
energy-dense
between March 1996 and
who the
in
1998,
milliliters,
volume,
April
Downloaded from pen.sagepub.com at MICHIGAN STATE UNIV LIBRARIES on February 26, 2015

353
for-
Tolerance
the Formulas
that all
received the standard
the total
of
assumption
patients
and, thus,
mula
(1
kcal/mL)
equaled
daily
the adminis-
Tolerance was assessed
tered volume of tube
expressing
by
of
who were
in
the child.
Patients,
energy requirements
the
of
percentage
as
a
feeding
to receive
the
randomized
fact,
formula,
energy-enriched
volume and
the occurrence of
required
vomiting.
by
of
received 150%
their
daily energy requirements.
Bothwererecorded
in
a
the
The
diaryby
parents.
daily
Thevolumewas
full
in 3
consec-
built upto
strength
recorded volume administered was not corrected for
was
because
utive
intractable
monitored,
days. Vomiting
carefully
The occurrence of
was divided into
vomiting.
vomiting
would indicate the need for
vomiting
and
other cause-
infection-related,
therapy-related,
ratherthan
aspiration.27
to
reduce
would consis-
volume
related andwas
transpyloric
nasogastric
in meannumberof
feeding,
expressed
days per
vomiting
per day
risk of
vomit
When
a
child
the
week.
the number
of
on which
Only
days
above
a
certain
occurred was evaluated and
not the
tently
volume, feeding
frequency
to
was reduced
the
tolerated level and or the volume.
in
and
wastreatedwithanti-
previously
when tolerance
of
increased
around
emetics.
when
improved. Vomiting
and
Weight
Height
chemotherapy
periods
were
used,
Furthermore,
promotility agents
and
measurements were
onward
Weight
height
performed
to reduce the occurrence of
necessary,
gastroin-
from
one
observer
for children
weekly
diagnosis
techniques. Height (length
wasmeasuredto the nearest 0.1 cm
by
using
The formula
testinal side effects.28
never diluted. If
to
was, however,
<
standard
of
2
a
child hadnot
sufficiently
responded
transpyloric feeding
years
a
age)
using
King-
have
these
would
measures,
stadiometer
United
determined
(Holtain
Ltd,
Crymych,
was
been initiated.
to
and
the nearest
dom)
(without clothes)
weight
Tube
was administered at home and
admission via
0.1
an
electronic scale
during
feeding
(Berkel,
kg using
silicone duo-
a
small bore
was
The
as
for
Netherlands).
a
z-score,
(9F),
hospital
denal
Ridderkerk,
expressed
Weight
according
height
to the Dutch refer-
tubewith
was
a
Ecouen,
after
auscultation
feeding
(Vygon,
weightedtip
for the child’s individ-
andwascorrected
ence
that
inserted into the
was verified
values,34
France)
which
stomach,
derived from the child’s
ual
z-score,
target
target
by
proper placement
indicated
a
deviation from
z-Scores below zero
over
the abdomen
air into the tube.
while
weight.
injecting
tube
infusion over a 24-hour
the child’s own
indicating weight
growth percentile,
was admin-
feeding
admissions,
During hospital
at
was
Malnutrition
loss and malnutrition.
defined as a
diagnosis
istered
all
in
continuous
by
period
>5%
from
of
loss
preillness body
weight
At
the
routine was flexible
home,
patients.
feeding
weight.
and was tailored
individual needs and
to
most
possibilities,
but
best-tolerated,
ultimately
patients preferred,
Body Composition
and thus received
continuous
feedings overnight by
infusion over a 10- to 12-hour
with
a
combined
and
measured at
skinfold
biceps
skinfold
(TSF)
period,
MUAC,
triceps
and at
2-hour
Nocturnal
stimulate
of continuous infusion
was started after
the child to eat
the
thicknesses were
(BSF)
diagnosis
period
during
in order to
day.
one observer
stan-
intervals thereafter
by
using
weekly
dinner,
feeding
Skinfolds were measured in
nearest0.1
dard
dinner. For
preferably
the same
adminis-
techniques.35>36
during
mm
a
skinfold
MUAC was measured to the
threefold to the
the
was
using
caliper
reason,
daytime
portion
and the
(Holtain
nearest 0.1 cm
both on the
Ltd),
lunch.
after
In someofthe older
tered
children,
feeding
feeding, pro-
administered,
a
nonstretchable
measure,
tape
using
to continuous
volume
was restricted
vided the
nocturnal
could be
arm.
arm
nondominant
muscle area
Upper
required
from the
thickness and the
TSF
was calculated
(AMA)
MUAC
of
to remove the tube
because
the
they preferred
and reinsert it
during
to Frisancho et al. 35 Measurements
according
in the
for
social rea-
ad libitum but did
administered.
evening,
day-time
sons.
TSF
were
and
thicknesses
below or above the standard
MUAC, BSF,
expressed
Oral
was
feeding
permitted
as
weekly
(P50)
of
percentages
the
oftube
influence
volume
not
All
feeding
10th
The
a
reference
of
MUAC
percentile
population.37
intake was recorded
in
a
food
The
and
oral
daily
diary.
of BSF andTSFthicknesses was consid-
and
amount
oftotal
(:::’:::20%
composition
daily energyrequirements)
for
but
achiev-
was
ered to be the cutoff
the 50th
malnutrition,
reference
point
of
oral
intake will be described
the
the near future.
Mucheffort was
energy
of
a
ing
the
percentiles
population
in
measure considered to indicate
only
adequate
on
the
ofthe
com-
15
achieving
highest
spent
repletion.
in the administration
volume. Parents were
pliance
possible
prescribed
to
weekly
provide
encouraged
prescribed
Proteins
Serum
their
were
child with the
volume and
Serum
allowedto call
occurred. To
dueto
the infusion rate was
at all times
ifanyproblems
transferrin,
prealbumin,
retinol-binding
pro-
for
tein
mined
and albumin concentrations were deter-
(RBP),
interruptions
feeding
maximallycompensate
medical
at
at initiation of tube
and
planned
procedures,
diagnosis,
feeding,
when
or the
fewhours onthe
of
weekthereafter
the
tolerated,
increased,
every
temporarily
period
during
study
During
period.
tube
before the
of
wasextended
a
fever and infection
4
these
no
(>38°C;
feeding
by
day(s)
periods
blood
days),
chil-
were
because
factors
(and
Furthermore,
taken,
are known to
influence serum
procedure.
samples
parents
when
were
howto insertthetube
time lost because ofinad-
concentra-
concentrations below the
dren),
willing,
taught
feeding
protein
to
were considered
in order
to minimize
tions. 17,18,38,39 Serum
lower limit of
protein
vertent extubation at home.
normal
the
range
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354
TABLE
I
indicate
considered to be
The normal
were
protein depletion.
ranges
characteristics at initiation
tube
of
Summaryof patient
feeding
follows: serum
0.17 to
as
prealbumin,
0.42
and
All blood
30to 60
35 to 50
2.2
3.6
to
transferrin,
g/L; RBP,
albumin,
mg/L;
g/L;
g/L. 40
were measured in the same labo-
samples
the same
under
and transferrin
control
concen-
technique,
ratory, by
quality
standards.
Prealbumin, RBP,
trations were
determined
by immunonephelometry
a
II
Cobas Fara
(Hoffmann-La
Roche,
using
Basel,
120
analyzer
a
for
and
Disc
for the
Switzerland)
prealbumin
Hyland
Nephelometer (Hyland, Bruges, Belgium)
serum
Albumin concentrations in
two
serum were
other
proteins.
determined
Hitachi
747
a
using
analyzer (Hitachi,
spectro-
and the
and
Certified Ref-
International
photometric
Brom-Cresol
transferrin
erence Material 470
Federation ofClinical
Tokyo, Japan)
Green
method.
RBP,
Prealbumin,
were
the
the
calibrated
against
of
(CRM-470)
Chemistry.
Protocol
andDose
the
Adherence
Reductions
For
ofdose reductions and
each
number
patient,
therapy
in
were
Per formula
recorded.
group,
delays
as the mean
the
andreductionswere
expressed
delays
over the 10-week
study period.
arm
for
MUAC,
circumference; WFH,
weight
midupper
height.
*Values are
means
SD.
from reference
tdifference
population.
Statistical
Analysis
The
SPSS (SPSS
to
If
datawasthe
statistical
used
analyze
program
Chicago,
were
data
IL).
Inc,
necessary,
in
the
formula
significantly
energy-enriched
higher
before further
to obtain &dquo;nor-
transformed
analysis
log
the whole and suffi-
covered the child’s
study period
group throughout
Differences in baseline
were
characteristics
mality.&dquo;
ciently
daily energy
requirements,
tested for
to confirm that ran-
differences
a
t test,
To
test
significance by
in contrast to
formula.
of84to
A
mean
standard
the
tube
daily
require-
domization had
between
means,
worked.
significant
14%of
intake
energy
by
feeding
a t test
or Mann
U
test was
Whitney
in the
ments was achieved
standard
formula
group
energy-enriched
whichever was
in
Relative
used,
appropriate.
changes
with
in
112%
group (t test; p
15%
the
compared
variables
and
in serum
pro-
anthropometric
changes
<
A
formula
mean
.001).
daily protein
concentrations after
4
and 10
tein
within and
weeks,
in
the
intake of 1.27
was observed
with
g/kg body weight
group
energy-enriched
allowance for
between
were
tested for
re-
groups,
by
significance
standard
formula
1.54
group.
compared
g/kgbody
ANOVA
2
To
with
deal
(RMA).
peated-measures
values,
missing
in
formula
Therec-
the
daily
weight
the values of
weeks were aver-
subsequent
ommended
was the same
protein
the
of
the
with
initiation of
value
at
in
aged,
exception
The
for both
i.12
namely
body weight.
groups,
g/kg
tube
If
a
value were
1
the
week,
feeding.
missing
subsequent
+
of fluids
recordedathomeand
ad libitum
intake
(tube
[in
daily
feeding
value in the
week
was used.
available
admission,
both
groups.
mold,
during
hospital
in
fluid
met
adequately
requirements
RESULTS
and
the
Tolerance
Formulas
of
Tube-Feeding
the
Intake
of
Description
Sample
Energy
of
The administered volume
tube
feeding, expressed
in
A
characteristics
in Table I.
initiation
were sim-
of
at
summary
patients’
as
a
of the
is shown
volume,
percentage
required
oftube
is
shown
Groups
feeding
1. Onaverage,
in
standard
the
formula
Figure
group daily
ume,
patients
because no
ilar on baseline
characteristics,
groups
significant
age,
sarcoma or
received 84%
14% of the
vol-
required
for
found
between the
differences
were
in
whereas
received
the
10%
the
formula
patients
energy-enriched
of
tumor load
distribution
disseminated
sex,
high
and
Ewing
75%
the
of
(t
.108)
test;
group
required
p
of
the
disease,
and biochemical variables.
any
anthropometric
volume,
during
study period.
of
The occurrence of
and the
vomiting
percentage
of
in
the different
which
occurred are shown
vomiting
patients
types
Intake
Tube
Energy
by
Feeding
was initiated 2.8
energy-enriched
in
II. Ahigh
Table
numberof
days
a
3.8 weeks after does not
or
Tube
diagnosis
after 1.6
feeding
in the
necessarily imply
high
only
large
frequency
and
formula
volume of
number of
the
because
occurredwastakeninto
was
days
In
group
vomiting,
2.6 weeks
in the standard onwhich
.38)
account.
(t
The mean
test;
p
vomiting
formula
intake
both
daily energy
per
group.
groups, vomiting
mainly therapy-related,
as
a
of the total
with no differences between
the two
week,
expressed
percentage
shownin
daily
groups. Therapy-
1.
intakewas related
requirements, is
Figure
wellto theuseof
antiemet-
Energy
vomitingresponded
Downloaded from pen.sagepub.com at MICHIGAN STATE UNIV LIBRARIES on February 26, 2015

355
FIG. 2.
the
in z-score of
for
formula
in the standard and
10 weeks of
Changes
weight
height
energy-enriched tube-feeding
group during
tube
formula
The increase in z-score in the
feeding.
energy-
in
nasogastric
than
the increase
enriched
was
group
significantlyhigher
group (repeated-measures
formula
ANOVA
the standard
between
.006).
groups:
p
Weight
WFH
illus-
tube
in the z-score
2.
the z-score increased
of
are
of
( SEM)
During
Changes
trated in
the first
4
weeks
Figure
in both for-
feeding,
significantly
in
mula
.003 and
the
respec-
groups,
.002,
(RMA;
p
p
groups
standard and
formula
energy-enriched
with no
Between and 10
difference between the two
tively)
groups.
continued to increase
riched
significant
4
the z-score ofWFH
Fm. 1.
mean
week
tube
intake
weeks,
Top:
daily energy
per
provided by
as
a
ofthe total
in the
daily energy require-
feeding, expressed
percentage
energy-en-
significantly
bottom: mean
oftube
administered
volume
ments ;
week,
daily
percentage
feeding
per
the
formula
whereas
no
was
(RMA;
.003),
group
p
group
a
as
ofthe
volume.
expressed
required
increase in the standard
This
formula
longer
resulted in
z-score of WFHin the
energy-en-
a
significant.
ultimately
significantly
in
increase
higher
and its occurrence was
than
richedformula
with
the standardfor-
ics,
significantly higher
group, compared
that ofinfection-related
and
related
mula
after 10 weeks of
tube
vomiting
vomiting
the occurrence
(RMA;
p
feeding
group
of
different
10
formula
WFH
in
&dquo;normalized&dquo; the
to other causes
infection-related
these
weeks
.006).
.001).
(p :5;
Only
significantly
During
inthe
butnot
standard
formula
was
energy-enriched
group
In the
vomiting
formula
2).
between the two
was not
The total occurrence of vom-
different.
group (Fig.
energy-enriched
groups.
11
of 15
increased their z-score
(73%)
to above
group,
from below
in the standard formula
patients
significantly
iting
with
2
of 12
(17%)
zero,
compared
not
of
Diarrhea did
seemto be anadverse side effect
of the children. In most
patients
group.
tube
in
children,
the
any
feeding
stools were less solid than usual
of tube
however,
during
Composition
Body
In the
children
younger
(<3
period
years),
feeding.
of
was
the first weeks
diarrhea
in MUACandin BSFandTSF
population,
present during
thicknesses,
Changes
after which it
shownin
are
weeks of tube
relative to the reference
administration,
disappeared.
Fig-
sig-
a
the first
4
ure 3.
nificant
During
feeding
increase in
andTSFthicknesses
in both formula
MUAC, BSF,
was observed
.001)
(RMA;p :!5;
groups,
groups.
II
TABLE
cause,
of
no
differences betweenthetwo
with
and the
in
patients
The occurrence
of
significant
of
by
vomiting,
percentage
which that
was observed
4
and 10 weeks of tube
Between
type
vomiting
however,
feeding,
increase
to
in
these variables continued
formula
significantly
in
where BSF
the
(RMA;
.001),
energy-enriched
group
p ~
contrast to the standard formula
group,
TSF
and
thicknesses remained stable or even
MUAC increased
and
This
increase
decreased,
(RMA;
only slightly
resulted in
a
.05).
p
ultimately
in
significantly
thicknesses,
with
tube
group MUAC,
with
Values are the meannumber of
the
week,
days per
percentage
and TSF
group, compared
MUAC,
BSF,
higher
of
in
the
of
on which
vom-
number
patients
parentheses. Only
days
frequency per day
in
the
formula
energy-enriched
occurred were evaluated and not the
or the
iting
the standard formula
after 10 weeks of
vomited volume.
group,
<
In
.05
the
formula
(t-test).
*p
feeding.
energy-enriched
Downloaded from pen.sagepub.com at MICHIGAN STATE UNIV LIBRARIES on February 26, 2015

356
FIG. 3.
folds
in
skin-
triceps and
Changes
and
biceps
and in
bot-
middle,
(top
respectively)
circumference
(MUAC;
midupperarm
in
the standard and the
formula
tom)
riched
energy-en-
tube-feeding
group, during
10 weeks
tube
under or
of
as
nasogastric
percentage
feeding,
above
expressed
the reference value
thesethree
The increase of
variables were
(P50).
anthropometric
all
riched
in the
significantly
higher
energy-en-
with the
formula
group, compared
standard formula
sures ANOVAbetween
group (repeated-mea-
groups:
p
.002,
<
and
p
.004,
p
.001, respectively).
and
BSF
normalized
whereas these
in AMA
thicknesses
after
and
5
Relative
in TableIII.
in both
and their
increases wereobserved
are
TSF,
4, 7,
changes
significance
variables all shown
weeks,
respectively,
Significant
the first
below the
in
4
remained
standard
the
weeks and were fol-
standard
(P50)
groups during
an additional
4
between
formula
lowed
increase,
group.
by
significant
10
in the
and
formula
weeks,
group.
in
energy-enriched
This was in contrast to the standard formula
group
III
TABLE
was
which
observed
a
borderline
increase
muscle area in children with
4
only
Relative
in arm
and 10 weeks
solid tumors
significant
after
changes
after 10 weeks of tube
of
.06).
Ultimately,
nasogastric tube feeding
(p
in AMA
formula
energy-enriched group.
the increase
the
feeding,
higher
appeared significantly
in
and
Protocol Adherence
Dose Reductions
in
occurred in
3
of 12
with
formula
(25%)
Delays
chemotherapy
inthe standardformula
patients
group, compared
Values are means
value
SD.
arm muscle area.
AMA,
6
of
in the
The mean number of
15
(40%)
group.
patients
energy-enriched
ANOVA for difference between stan-
*p
repeated-measures
was not
delays
signifi-
dard
and
formula.
energy-enriched
increasewithin
different between the two
did not
Dose reduc-
<
cantly
groups.
ANOVA;
·’‘Significant
.05).
group (repeated-measures
p
tions
the
in
of
occur,
during
study period,
any
Downloaded from pen.sagepub.com at MICHIGAN STATE UNIV LIBRARIES on February 26, 2015

357
in
the standard
and the
energy-
FIG. 4.
enriched formula
in serum
albumin concentrations
increased
Thelowerlimit ofthe normal
retinol
tube
differences betweenthe two
and
prealbumin, transferrin,
10 weeks
binding
feeding.
Changes
protein
4
2
to
weeks
All serum
the first
group, during
of nasogastric
proteins
significantly during
<
withno
is shownfor each serum
range
.05)
(RMA; p
significant
groups.
protein
(horizontal line).
in
the
the
formula
the standard formula
and formula
both
cancer
is needed to
(1.5 kcal/mL)
patients
energy-enriched
in
adequately improve
in children with
oftreatment. To our
group
group.
in
1
and
only
patient
weight
body composition
the intensive
during
phase
Proteins
Serum
no
data are available
the effect
formulas on
the nutri-
knowledge
comparing
in mean
and albumin concentrations
serum
of two different
transferrin,
Changes
prealbumin,
tube-feeding
10 weeks of tional status ofchildrenwithcancer
this
RBP,
during
are shown in
no
during
period.
tube
4.
differ-
Because
studies have shownthat the absence
feeding
nasogastric
Figure
previous
will
a
deterioration of
Between the two formula
ences were observed in the concentrations at initiation
of nutrition
support
lead to
most children with
groups,
significant
in
a
nutritional status
cancer,’, 2,15
of
tube
and in the
of the serum
control
without nutrition
wasnot added
feeding
changes
pro-
group
support
teins after initiation of tube
At initiation of
and RBP
the lower limit of
for ethical reasons.
of
feeding.
nature of
caloric
tube
serum
Because
the
randomized
transferrin,
double-blind,
it was to
not
feeding
prealbumin,
the
concentrations were below
the nor-
weeks,
study,
so
provide equal
possible
2
As
first
the
and RBP concentrations had
volumes were
was to be
mal
serum
in both
levels,
range
groups. During
equal
provided.
a
from
the
of
studies,19,2S-27
expected
previous
prescribed
monitoring
compliance
not
prealbumin
<
in
100% of
increased into the normal
after which no
both
volume was
achieved,
range
groups (p
careful
and
adminis-
occurred.
.02),
significant changes
increased
despite
protocolized
Serum
tration. Thesemeasures
haveincreased
because
approx-
transferrin concentrations
within weeks in the
however,
may,
energy
signifi-
thus
(and
84%ofthe
2
formula
intake),
cantly
group
group
compliance
energy-enriched
4
in
volume ofstandard
and within
and continued to increase until
After this initial
weeks
the standard formula
(iso-
com-
al. 26
imately
prescribed
formula was administered in this
6
weeks after
tonic)
study,
with 67% in
a
Keohane et
initiation of tube
increase,
in both
study by
feeding.
pared
serum
in
studybyAbernathyet
only 61%
transferrin
a
concentrations decreased
al,25
Furthermore,
the
of
energy
was
Serum albumin concentrations increased in
of
amount
administered
groups.
both
required
98%
of
(mean
but the
with
both
increase was within the normal
groups,
compared
approximately
in
this
range.
study.
not
groups)
Compliance
two
different between
was
(84%
significantly
DISCUSSION
us
Wemay,
con-
the
for-
the
clude
increased
75~/c).
therefore,
formula,
energy-enriched
groups
with the standard
The
istration
results ofthis
show
admin-
that
that,
compared
study
ofan
long-term
of the
(10
weeks)
energy density
energy-enrichedtube-feeding
Downloaded from pen.sagepub.com at MICHIGAN STATE UNIV LIBRARIES on February 26, 2015

358
mula did not lead
increase in
a
in
decrease
to an
the volume administered has
which
stores and
continuation ofthe
fat
of
gastrointestinal
slight
lead to accelerated
stores would
muscle
side
to be
the occurrence of
dueto
eventually
wasting
effects,
with
reduced.
the fact that
differ-
proteins.
significantly
Together
was not
These data do not
that the stan-
necessarily imply
vomiting
significantly
the
se is inferior to
dard formula
energy-enriched
the two
find-
per
greater
ent between
ings
our data confirm
groups,
the stan-
have
formula.
A
of nutrients
by
provision
fromKeohaneet
which
nodiffer-
showedthat
al,26
in
dard
resulted in
dueto anincrease
formula,
volume, might
in
ence
intolerance was
gastrointestinal
hyperosmolar
appreciated
a
similar to the
formula.
weight gain
the
weight gain
and
A
between
osmolar
intake
isotonic formulas.
led to
hyper-
energy
achieved
this
in
However,
by
energy-enriched
a
formula, therefore,
higher
this
of
of
group
patients during
phase
treatment,
was
volumes are
(when
which,
repletion
equal),26
naturally,
this
the administered volume of standard formula
of
resulted in
nutritional
(in
superior
a
incapable
meetingenergyrequirements, indicating
study).
Even
in the
maximum
tolerated volume. Volume
to
appears
all
of
(ie,
therapy-re-
cause-related)
was not
though
types
vomiting
be the main determinant of tolerance and not
energy
and other
lated, infection-related,
in
of
as
been
assumed.26
has
Therefore,
density,
the
increasing
occurred
the
majority
patients, vomiting
intakevia the standardformula
increas-
by
energy
the
troublesome. This
that found
andtolerated
confirmed data from other
studies
in
withthecurrent
administration
ing
volume, would,
tube
to be
nasogastric
feeding
acceptable
not be tolerated. Smith et a121 also
found
schedules,
childrenwith
intensive
cancer,
by
during
that
volumes of isotonic
nasogastric
large
feedings
or bone marrow
chemotherapy
transplantation. 21,11
well
volume and
increase
in children with
in
tolerated children with cancer.
were not
The
well to antiemetic
reduc-
Vomitingresponded
of the standard formula
therapy,
efficacy
might,
treatment
or
in
tions
volume of
the use of
and
another
feeding,
promotility
however,
during
phase
We
no
believed that
a
disease other than cancer.
was,
means,
agents.
vomiting
by
intractable and
of
not
increase the risk
Continuation oftube
in the
weekswould
did
feeding
significantly
energy-enriched
was no need to initiate formula
after 10
result
in
recom-
there
aspiration. Therefore,
group
probably
an excess of
mended to
decrease the volume of
and fat. It
in
ofthe
is, therefore,
transpyloric
patients. 27
weight
feeding
any
Studies
of
in cancer
have
patients
body
energy-enriched
composition
of tube
to theextentthatthe administered
demonstrated that
fat is the
major component
feeding
energy
WFH
individual
percen-
body
loss4,7,8,42
mechanisms
is able to maintainthe child’s
with
mass.
as
weight
protect
compensatory
the
the needto use themas
fat stores and muscle
tile,
protein
body
body
corresponding
proteins,
byreducing
a
source of
of
fat.43 When
at the
body
energy,
expense
fat stores
becomes
continues and
Because ofthe absence ofreference data for AMAin
are
used
wasting
up, protein
accelerated
it is
with all the
Dutch
of muscle
difficult to commentonthe
at initiation of tube
children,
coinciding
impera-
restore
to
degree
markedly
feed-
It
is, therefore,
negative implications.2,14,43,44
protein depletion
are
to
fat stores or
the
withthe achievementof knownwhetherthe
American reference
which
tive
maintain
available,
data,
body
ing.
adequate
is not
because it
inten- have to be
with
fat stores
oftreatment.
initial,
caution,
throughout
depleted body
applied
ofAmericanchil-
sive
a
phase
body
Along
composition
child’s
dren resembles that of Dutch children.
these reference values were
would show
than the
however,
these
body
If,
target weight,
ofnutrition in
weight greater
this is one ofthe
to our
data,
applied
general goals
support
both
children
In the
cancer. 2,9,11,45
energy-enriched
at initiation oftube
the use
with
that,
feeding,
mini-
store had indeed been
energy
formula
of
as an
group
general
protein
of nutrition
were attained after 10 mized at the
of fat
AMA
because AMAwas
stores,
goals
support
protein
expense
below the
were
weeks.
and
restoration
and an increase in muscle
intakes
sufficient for
offat
mass
of the reference
in the of
presence
only slightly
tion not
popula-
Energy
of
(data
skinfold thicknesses.
shown)
loss,
metabolism,
weight
considerably
repletion
stores,
the
protein
during depleted
intensive
in skinfold thicknesses did
oftreatment. The increase
Because
available
data on
all the children
and
were
initial,
preillness
for
weight
in
the
height
phase
not lead to
excessive
weused the
fat,
study,
did not exceed the child’s WFH
to
inasmuch as skinfold thicknesses
determine
by
percentile
history
target
weight
which was considered extra
of In
loss at
and the
for nutrition
standard
(P50)
>10%,
diagnosis
weight
by
Wefound this
the 50th
to
of WFH of
more
intensive
be
accurate
energy storage during periods
therapy.
support.
approach
percentile
standard formula
both
and fat than
a
the
reserves were
healthy
who,
percen-
aboveor
group
weight
using
not
restored
reference
for all children. Children
for
after 10 weeks.
intake
adequately
population
4
and 10weeksoftube
meetmetabolic
decreased
have
beenon the 10th or 90th
a
Between
was not
instance,
feeding, energy
always
wouldbe
WFH
enoughto
assigned target
to
inasmuch
fat stores
tile of
demands,
weight
below the
as skinfolds
their individual
would not be accu-
and TSF thick-
target weight according
slightly. Apparently,
in
and
loss
were used as additional source of
order to
intake
energy
growth percentile,
weight
the use of
even
was more than sufficient. This resulted in an increase
assessed. For
MUAC, BSF,
spare
protein,
though protein
rately
reference data from
a
were
nesses,
usedto
healthy population
on
in muscle
in
mass concomitantwith
can be concluded from the borderline because
a
decrease
information
provide
the
of
protein
as
degree
depletion,
fat
increase AMAand MUACbetween
no
data were
available for these
stores,
preillness
in
4
and 10 weeks.
variables.
A
A
similar
low
observation
a1.46
fat
In
enced
was described
Fomonet
children with
can be influ-
weight
cancer,
by
body
reserve due
to insufficient
fluid
and
tumor mass.
energy
edema,
repleted
by
retention,
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359
of fat and skeletal
influenced
with the standard formula does not contribute to an
the loss
can mask
These factors
in serum
effects of malnutrition
withcancer are nodifferent fromthose seen in noncan-
concentrations.
additional increase
is not
or edema and
muscle.3,47 The
limb
protein
by
directly
upper
in
As the
be used as
moreaccurate andcom-
tumor
additional
mass
general
patients
can, therefore,
a
methodto
provide
cer
in
all
be of
malnutrition should be
of
patients,
prevented
therefore,
might,
characterization
skinfold measurements
body
composition. Biceps
plete
of
data
These
groups
use
patients.
an esti-
and
mate
provide
triceps
of
area can
in
children who are malnourished because of
whereas arm muscle
reserves,
estimate of muscle
fat
as
the
body’s
serve
causes other than cancer. Children with the human
protein
for
have increased
children.
virus,
requirements
instance,
immunodeficiency
As in
a
Rickard et
reserves.3,10,lS,20,3S-37,47
study
by
with
energy
compared
healthy
ourdata
that
a
al 16
nutrition,
suggest
parenteral
using
Astudy
of
tube feed-
the effects
assessing
nasogastric
ofchildren showed that tube
AMAand
in skinfolds
evaluation of
combined
changes
in this
ing
group
feeding
information on the
of
can
efficacy
provide important
was able to
unableto
was
and arm fat area but was
improve
significantly
weight
tube
feeding.
AMAeven
increase
tube
of 8.5
though
rate
influence
mayalso
status
changes
mass
Tumor
in nutritional
lism.
(the
its influence on metabo-
of)
administered over a mean
months.49 Administration of the
feeding
period
through
for-
energy-enriched
the
ofthis
to
It was, however,
beyond
scope
study
mula in these
result in
a more
patients might
rapid
signifi-
issue.
the random-
elaborate further onthis
Because of
of
a
nutritional
ofmuscle
status, including
improvement
cant
it was assumed that tumor
ized nature of the
study,
improvement
proteins.
was
divided between the two formula
not considered
load
It is concluded from this
that
intensive
equally
was,
study
during
of an
and
anticancer
riched
ent from that of
the
tolerance
therefore,
for the observed difference
tumor on basal metabolic
responsible
groups
treatment,
energy-en-
in
Theeffect ofthe
formula is not
standard formula.
tolerated volume of standard formula was not able
the child with its total
differ-
efficacy.
rate
significantly
tube-feeding
a
the
(BMR)
was, however,
However,
to
in
whowere
ofchildren with solid
older than the children
studied
another
tumors,
in
this
group
energy require-
the
provide
daily
considerably
the increased
ments. Because of
These
which showed BMRto be increased
energy density,
data,
study.
same volume of
meet the child’s
formula was able to
and
elsewhere.
at
will be described
from other studies
energy-enriched
energy
diagnosis,
Data
that nutrition
suggest
sup-
and
requirements
compensate
lost because of
and
bone marrow
for
attenuate
may
suppression
energy
intolerance. The
feeding interruptions
port
administration of an en-
tolerance.
Furthermore,
long-term
improve chemotherapy
it may
and reduce the occur-
formula
more
immune
(1.5 kcal/mL)
is, therefore,
ergy-enriched
effective than
improve infections. c2,o4m8petence
in
can-
rence of
In this
no dif-
a
standard formula
(1 kcal/mL)
the nutritional status of
however,
study,
was
children
with
ference in treatment
and dose reductions
delays
improving
the two formula
and occur-
cer
the intensive
of
as this
recommend
administration of an en-
observed between
in
groups,
be
during
treatment,
phase
low. This
were
was
demonstrates.
We, therefore,
rence,
may
included
explained by study clearly
general,
in
the fact
most
the
that
that
intensive,
patients
study
protocolized
tube-feeding
first
of
whereas treatment
at
the
calculated
formula,
stage
therapy,
ergy-enriched
during
delays
during
are
and dose reductions
later of
courses
more
to occur 150% ofthe child’s total
number of
is
likely
daily energy
requirements,
after
a
in chil-
the
initiated and continued for at least 10 weeks
therapy
havebeen
stages
administered. This is
with treatment
dren with solid tumors as soon as one ofthe
criteria is met.
inclusion
chemotherapy
fact that
the
confirmed
by
patients
received more bone
courses before
marrow
had
delays
already
sup-
entered
ACKNOWLEDGMENTS
chemotherapy
being
pressive
into the
in which no
than
were observed.
treatment
study
patients
We thank Numico Research BV for their financial
in
Patients
whom treatment
delays
for
distribution ofthe
and
and
the
support
preparation
formulas.
included into the
occur were
did
study, approx-
delays
nasogastric tube-feeding
3.9 weeks after
treatment
whereas
5.0
diagnosis,
imately
patients
were included after
without
1.8 weeks
delays
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