Oral Rehydration Therapy for Acute Diarrhea in Ambulatory Children

Oral
Rehydration
Ambulatory
Therapy
for Acute
Diarrhea
in
Children in the United States:
A Double-Blind
Solutions
Comparison
of Four
Different
Mathuram
Santosham,
MD, MPH, Barbara Bums, PNP, MPH,
Vinay Nadkami,
BS, Stephan
Foster, Pharm D, Steven Garrett, RPh,
Larry CrolI, RPh, J. Crosson
O’Donovan,
MD, Radha Pathak, MD, and
R. Bradley Sack, MD, ScD
From the Division of Geographic Medicine and Eudowood Division of Pediatric Infectious
Diseases, The Johns Hopkins University School of Medicine; Departments
of Pediatrics
and Medicine, Francis Scott Key Medical Center (formerly Baltimore City Hospital) and
The Johns Hopkins University School of Medicine, Baltimore, and US Public Health
Service Indian Hospital, Whiteriver, Arizona
ABSTRACT.
Oral rehydration
solutions
containing
50 to
90 mmol/L
of sodium
have recently
been recommended
for the treatment
of diarrhea
in both hospitalized
and
ambulatory
children
in the
available,
however,
fore, we conducted
paring
United
States.
Few
data
are
from ambulatory
US children.
Therea randomized
double-blind
study com-
the use of four different
oral rehydration
solutions
with differing
concentrations
of sodium,
glucose,
and
base. Ambulatory
children
less than 2 years of age with
acute diarrhea
(N = 140) were randomly
chosen to receive
solutions
containing
sodium
at 90 (solution
A), 50 (solution B), and 30 mmol/L
(solutions
C and D). All oral
rehydration
solutions
solution
A contained
other
contained
D which
contained
bicarbonate
three
contained
20 g/L
50 g/L
as its
citrate.
except
of glucose
of glucose.
base
source
All but three
Solution
whereas
(98%)
the
children
were treated uneventfully
according
to the study protocol,
and there were no differences
among groups in measurements
of clinical
outcome.
It was concluded
that in amUS children,
oral rehydration
solutions
containing 90, 50, or 30 mmol/L
of sodium
can be used safely for
the treatment
of mild acute diarrhea
and that citrate
is
as efficacious
as bicarbonate
in the correction
of acidosis.
bulatory
Pediatrics
1985;76:159-166;
oral rehydration,
diarrhea,
Received
for publication
The opinions
and
do not
expressed
necessarily
June
oral
rehydration
dehydration.
6, 1984;
in this article
reflect
the
solutions,
of the
patients
in
Indian
Health
Service.
have
also
been
with
the
tion
solutions
of acute
States’
of these
and
oral
successfully
use
in
developing
rehydration
used
of standard
for
solutions
nehydration
of
solutions
rehydration
commercial
oral
used
for the
management
United
States.
commonly
diarrhea
in the
containing
and
in the United
marketed
oral
50 to 90 mmol/L
maintenance
therapy
rehydra-
States
have
rehydration
of sodium
for
in ambula-
tony patients.
However,
pediatricians
in the United
States
are reluctant
to use these products
because
their
safety
and efficacy
have not been tested
in
tinue
American
of sodium
of Pediatrics.
United
Both
well-nourished
ambulatory
infants
suffering
from
acute
diarrhea
in Panama.5
However,
no data are
available
comparing
the use of these two solutions
Reprint
requests
to (M.S.)
Division
of Geographic
Medicine,
Francis
Scott Key Medical
Center,
4940 Eastern
Aye, Baltimore,
MD 21224.
PEDIATRICS
(ISSN 0031 4005). Copyright
© 1985 by the
Academy
the
countries.4
A number
ofcompanies
recently
produced
and
accepted Oct 2, 1984.
are those of the authors
views
Recent
studies
have demonstrated
the safety and
efficacy
of oral nehydration
solutions
containing
90
mmol/L
of sodium
and 20 g/L of glucose.
These
concentrations
of glucose
and sodium
have been
recommended
by the World
Health
Organization
(WHO)
for hydrating
hospitalized
infants
in both
developing
and developed
countries.’3
It has also
been
shown
that
an oral
rehydration
solution
(ORS)
similar
to the WHO-ORS
in its composition
except
for its reduced
sodium
concentration
(50
mmol/L)
can be used safely to hydrate
hospitalized
ambulatory
to
dration
US
be
children.
concerned
solutions
containing
in minimally
PEDIATRICS
These
about
pediatricians
the
use
“high”
dehydrated
Vol. 76 No. 2 August
Downloaded from www.aappublications.org/news at Indonesia:AAP Sponsored on July 23, 2021
of oral
conrehy-
concentrations
ambulatory
pa-
1 985
159
tients.6’7
They
in ambulatory
fear that
US children
the
use of these
solutions
may induce
hypennatre-
mia.
treat
Therefore,
ambulatory
many
patients
pediatricians
who have
with
solutions
containing
low
sodium
(25 to 30 mmol/L)
ofglucose
(5%
In 1982,
rheal
and
continue
to
acute
diarrhea
concentrations
a high
a group
of experts
concentration
the
sodium
and
mented
tenance
with free water
for nehydration
therapy
in ambulatory
patients
2%
diarrhea
developing
were
in
based
many
on the
both
in the
These
on extensive
clinical
However,
recommended
unlikely
from
rehy-
mmol/L
of
supple-
studies
and
US
developing
States
seven
and
pediatricians
and
trained
solutions
containing
50 and
should
be tested
in ambulatory
we
comparing
the
differing
base
in
(Table
diarrhea.
g/L
(2% or 5%)
ability
in two
ORS
and
was
TABLE
This
were
studied
solutions,
for
in
comparison
Oral
storage
Rehydration
S
Made
B,
C,
and
D
in
the
first
160
ORAL REHYDRATION
4%;
tn-glucose,
5%;
tended
All
cit-
Used
90
20
0
0
80
0
30
0
20
80
333
50
20
4
4
50
23
0
5
20
80
251
30
20
4
4
30
23
0
5
20
80
211
30
20
4
4
30
28
0
0
50
200
388
tetra
and
FOR
in
Albert
Out-
Key
Medical
City Hospitals),
of the Johns
ComHopkins
Pediatric/Medical
Whiteniver,
population
Arizona.
residing
The
study
Fort
period
1983.
by
of the
was
meeting
parents
This
on the
May
1, 1981 to April
30,
were
initially
examined
one
in the
Public
ex-
the
pni-
investigators.
obtained
from
the
the above
criteria.
Chilwere randomly
assigned
of four groups:
A, B, C, or D. The randomicode was maintained
at our Baltimore
office
or the
pharmacy
the
Patients
vided
US
protocol
study
Public
Arizona.
to the persons
Treatment
solutions
solutions
of the
Whiteniven,
study
until
DIARRHEA
Baltimore:
to one
zation
the
di-
in
Pediatric
were also enrolled
clinic
of the US
Hospital,
parents
of patients
dren of consenting
so-
to enrollment
were
recruited
Scott
Witzke
children
outpatient
many
cane physicians
or
Written
informed
consent
available
(Frodex
1%;
from
patients
Hospital,
higher-glucose,
ACUTE
and
five
Patients
clinically
rehydration
sites
Baltimore
Care Clinic
than
least
dehydration
had
received
(J.C.O.),
Francis
Reservation.
except
study
the
Indian
D
the
of
Apache
C
of
Clinic
the
in solution,
mono-glucose,
following
office
serves
B
contains
the
practice
Service
A5
phase
Laboratories]
study
hospital
the following to 1 liter of water: sodium
3.5 g; sodium
bicarbonate,
2.5 g; potassium
1.5 g; and glucose,
20 g.
polymer
used instead
of glucose
for solutions
[Wyeth
glucose,
90%).
at
private
Health
by adding
chloride,
chloride,
t Glucose
the
one
(at
oral
of age
(less
or severe
if they
or
above
2 years
acute
illness
prior
children
with
Study
Sodium
(mmol/L)
Potassium
(mmol/L)
Magnesium
(mmol/L)
Calcium
(mmol/L)
Chloride
(mmol/L)
Citrate
(mmol/L)
Bicarbonate
(mmol/L)
Phosphate
(mmol/L)
Glucose
(g/L)t
Calories
(/L)
Osmolality
(mosm/kg)
for
than
24 hours).
if they were
a commercial
diarrheal
Eighty-one
and
Because
Solutions
with
well-nounpublished
for Health
diarrhea
in the previous
from the study
Fifty-nine
from
the
WHO-
solutions
powder
weight
standards
Center
with
watery
lution
for the
into the study.
and
less
seen
Clinic.
study
avail-
the
Laboratories).
is unstable
Four
of their
treatment
Hospital,
of 20 or 50
because
used
(Ross
the
patients
were
duration)
Center
(formerly
prehensive
Child
at
glucose,
concentrations
commonly
used
1.
sodium,
who
initially
to have
moderate
standard
criteria’
patient
study
solutions
1) in ambulatory
Pedialyte
bicarbonate
rate
nehydration
of
Glucose
90 mmol
US chil-
a double-blind
of oral
concentrations
source
acute
conducted
use
were
days
assessed
using
the United
States
unless
they are shown
to be safe
and efficacious
in treating
US children.
In addition,
a recent
editorial9
suggested
that
the use of oral
rehydnation
of sodium
dren.
Therefore,
in dry
of 140
(height
according
to
States
National
1976)10
who
consisted
children
watery
stools
were excluded
committee8
countries
population
Statistics,
rehydration
expert
study
ambulatory
third
percentile
by the United
and mainsuffering
conducted
oral
The
ished
recommendations
the
by
60
United
the
by
to be used
pediatricians
to
is packaged
METHODS
of dian-
WHO-ORS
countries.
countries.
solutions
are
glucose
50
which
Patients
of oral
solutions
in
containing
use
dration
acute
of
in treatment
recommended8
WHO-ORS,
form.
to 8%).
diseases
from
in the
responsible
or the
was
Health
This
code
Service
was
not
for conducting
parents
of study
patients
concluded.
Groups
in
groups
A,
B,
C,
and
D were
given
A, B, C, and D, respectively
(Table
1). All
except
solution
A were prepared
and pro-
by Wyeth
of solution
A were
Health
Organization.
Laboratories.
The
provided
in packets
Solution
A was
dry
ingredients
by the World
reconstituted
by either
a pharmacist
at the US Public
Health
Service
Hospital
at Whiteniver
or an individual
at
our Baltimore
office
(neither
of these
individuals
Downloaded from www.aappublications.org/news at Indonesia:AAP Sponsored on July 23, 2021
participated
in conducting
the clinical
trial)
by
mixing
the appropriate
prepackaged
ingredients
with tap water
to a total
volume
of 1 liter. The
reconstituted
solution
was dispensed
to the patient
in 8-oz (.03 L) bottles,
which
were identical
with
those containing
solutions
B, C, and D provided
by
the manufacturer.
During
the first phase
of the study
(N = 49) in
Baltimore
(May
1, 1981 through
April
30, 1982),
the manufacturer
had used a glucose
polymer
instead of plain
glucose
in solutions
B, C, and D in
the same concentrations
(Table
1).
All patients
were given 8-oz (.03 L) bottles
of the
appropriate
oral rehydration
solutions
in quantities
of approximately
200 mL/kg
to be used in a 24hour period.
Infants
less than
12 months
of age
were also given
1 liter of soy-based
formula
every
24 hours
(Nursoy,
Wyeth
Laboratories)
unless
the
infants
were breast-fed,
in which case breast-feeding was continued,
and parents
of infants
older
than 12 months
were instructed
to use non-lactosecontaining
the
fluids.
Mothers
were
instructed
rehydration
solution
ad libitum
up to the
amount
dispensed
every
24 hours
as long as the
child was having
watery
stools,
and to alternate
it
with
the formula
or breast-feeding.
After the thanrhea had resolved
(no watery
stools in the previous
eight hours),
the oral rehydration
solution
was discontinued
and the patient
was returned
to a regular
diet.
Patients
were seen every day either
at clinic
or
at their home until the diarrhea
stopped.
Total body
weight
was obtained
on admission
to the study,
daily until the diarrhea
resolved,
and 2 weeks after
initial
presentation.
During
the follow-up
clinic on
home visits,
the amount
of oral rehydration
solution
remaining
in the bottles
was measured
by one
of the study
staff. The volume
of soy formula
remaining
in the liter
can was also measured
when
available.
If the can was not available
for inspection,
the mother
was asked
about
the volume
of
formula
ingested
by the infant.
Patients
were considered
to be treatment
failures
after 24 hours of therapy
if their degree
of dehydration was considered
to be more than 5% (by clinical
at any
of the
or weight
loss)
were found
follow-up
or if their
serum
to be abnormal
visits.
for
enteric
Escherichia
teniologic
cultures
from
from
were obtained
bicarbonate,
teins,
and
and
hematocnit)
Laboratory
cluded
blood
(see
electro-
potassium,
blood
mens
chloride,
urea
were
enzyme-linked
nitrogen,
examined
immunosorbent
total
hematocnit.
rotavirus
assay”
chloride,
serum
pro-
after
(no
initial
watery
visit
stools
in
Methods
Analysis
of variance
testing
when
ysis was used
(ANOVA)
was
performed
on
en’s
exact
x2 anal-
ANOVA
showed
significance.
on frequency
data
except
analysis
was
more
when
Fish-
appropriate.
RESULTS
All but three
of the 140 children
were treated
successfully
according
to the protocol
of the treatment
group
into which
they had randomly
been
assigned.
Clinical Comparison
(Tables 2 to 4)
protein,
Stool
antigen
and
on Admission
At the time of admission
to the study, there were
no statistically
significant
differences
in clinical
characteristics
within
the population
groups.
A bactenial etiologic
agent was identified
in 20% of the
99 infants
who had bacterial
cultures
done. Sixteen
of the
20 positive
bacterial
cultures
contained
en-
terotoxigenic
E coli, six from
Baltimore
and ten
from Whiteniver.
Nineteen
of the 118 (16%) stool
samples
tested
for rotavirus
antigens
were positive.
An
etiologic
(35%)
agent
patients
was
in whom
thus
identified
both
bacterial
rotavirus
antigen
assays
were
tients
were receiving
antibiotics
enrollment
in the
Clinical Course
on admission
inlevels of sodium,
bicarbonate,
and
for
hours
pa-
studies
appropriate
variables
among
treatment
groups
at
each site, among
treatment
groups
between
sites,
and among
treatment
groups
after the data were
merged,
followed
by Newman
Keuls multiple-range
percentage
performed
for serum
81 (53%)
in 28 of 80
cultures
and
performed.
Four
paat the time of their
study.
below)
Studies
studies
sampling
24
bac-
patients
laboratory
(serum
sodium,
potassium,
blood urea nitrogen,
total
Comparisons
Laboratory
for
all
43 of the
and at resolution
of diarrhea
previous
eight hours).
Statistical
on
Follow-up
enter-
samples
collected
from
Baltimore.
including
Stool
12
were
Whiteniver
tients
pathogens,
to give
oral
assessment
lyte values
niologically
otoxigenic
speciby the
bacte-
weight
of Illness (Tables
5 and 6)
of intake,
of diarrhea,
and
among
four
gain
duration
were
made
the
treatment
groups
in the two phases
of the study.
The mean intake of sodium
during
the first 24 hours
and throughout
the entire
illness
was significantly
higher
in group A compared
with the other
groups
(Table
5). Also,
group
A patients
gained
significantly
more weight
than
group
C patients
by the
ARTICLES
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161
TABLE 2.
Features
Clinical
of Fo ur Treatment
Group
(n =
Mean age (mo)5
Sex (M/F ratio)
Mean body weight
tion (kg)5
No. with history
Mean
No.
at resoluof vomiting
of days
of diarrhea
by initial visit5
No. with temperature
>38.5#{176}Con initial
No. given antibiotics
initial
visit
prior
Values
are means
listed used
t Three
A, two
at T ime of Admi ssion
Group
B
Group
C
(n = 35)
(n = 36)
9.6 ± 0.9
9.7 ± 1.1
9.5 ± 1.1
1.4/1
1.9/1
1.8/1
8.4 ± 0.4
8.8 ± 0.4
8.5 ± 0.4
34)
to Study
Group
D
(n = 35)
± 1.0
1.5/1
8.9 ± 0.4
9.8
16 (47%)
15 (43%)
12 (33%)
12 (34%)
2.0 ± 0.2
2.8
2.3 ± 0.2
2.3 ± 0.2
± 0.3
2 (6%)
5 (14%)
4 (11%)
3 (9%)
2 (6%)
1 (3%)
0
1 (3%)
2
2 (6%)
0
2 (6%)
1
2 (6%)
32 (94%)
33 (94%)
34 (94%)
to
visit
No. breast-feedingt
No. with degree of dehydration 5%-7%
No. with <5% dehydration
S
Groups
A
in group
B, and
of milk and
D = 2).
also
TABLE
Laboratory
3.
± SE.
only breast.feeding
during
two
for source
in group
illness
D) used
used
breast-feeding
of Four
Features
of milk.
Five
breast-feeding
other
and
and
Groups
35 (100%)
infants
(one
in group
formula
as regular
source
(A = 1, B = 2, C = 0,
soy formula
Treatment
0
0
at Time
of Admission
to
Study5
Group
A
Group
(n=34)
Serum
Serum
Serum
Blood
sodium
(mmoi/L)
potassium
(mmol/L)
bicarbonate
(CO2) (mmol/L)
glucose (mg/dL)
Blood urea
Hematocrit
Total
S
136.7
4.8
15.4
84.4
10.1
37.2
nitrogen
(%)
serum
Values
TABLE
protein
are means
4.
(g/dL)
Enteropathogens
Isolated
from
Group
Rotavirus
Salmonella
5/29
Shigella
Campylobacter
Enterotoxigenic
7/25
coli
Bacterial
136.9
± 0.5
137.9
4.7 ± 0.1
16.0
±
±
±
±
±
87.1
9.6
36.9
6.9
Group
0.5
2.5
0.7
± 0.4
16.2
85.5
10.1
±
±
±
36.0 ±
6.6 ±
0.4
0.1
D
(n=35)
137.5
4.6
16.2
82.6
9.7
±
±
±
±
±
37.2 ±
6.7 ±
4.8 ± 0.1
Four
Groups
A
0.6
2.7
0.7
0.5
0.1
0.6
0.1
0.8
2.6
1.0
0.5
0.1
of Patients5
Group
(17%)t
0
0
0
5/31
3/22
(28%)
B
Group
3/28
1/22
(16%)
(14%)
0
(5%)
6/18
(33%)
2/24
cultures
were performed
3
2
2
3
2
1
for 99 patients
(70.7%)
with
C
Group
(11%)
0
0
0
6/30
(8%)
1/24
1/25
D
(20%)
0
(4%)
0
(4%)
resolution
of illness
(Table
6). There
were no statistically
significant
differences
between
the groups
in any other
measurements
in both phases
of the
study.
All of the groups
demonstrated
either
no or
minimal
(1% or less) weight
gain after 24 hours
of
therapy.
Serum
0
1
0
0
1
ELISA
(84%)
for a pathogen
(enzyme-linked
with 19 positive
Electrolytes
None
Na4
<125
1
20 positive
(20%).
(One culture
was positive
for two bacterial
pathogens.)
immunosorbent
assay) for rotavirus
was performed
for 118 patients
(16%). (Three
patients
also had positive
bacterial
cultures.)
t Indicates
number positive/number
tested.
162
C
(n=36)
(ETEC)
Heat-stable
enterotoxin
Heat-labile
enterotoxin
Both enterotoxins
5
Group
± SE.
Pathogens
Escherichia
± 0.7
± 0.1
± 0.7
± 3.0
± 1.0
± 0.5
6.9 ± 0.1
(mg/dL)
B
(n=35)
of the
patients
was
hypernatremic
>150
mmol/L),
hyponatnemic
mmol/L),
hyperkalemic
(serum
L) or hypokalemic
(serum
K <2.5
ORAL REHYDRATION
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www.aappublications.org/news
(serum
(serum
Na’
K >6 mmol/
mmol/L)
on the
TABLE 5.
Intake
of Fluids
During
Therapy
for Four
Group
Groups
of Patients5
A
Group
(N=34)
First
24-h
intake
treatment
intake
intake
solution
B
Group
(N=35)
C
Group
(N=36)
D
(N=35)
67.6 ± 8.2 (34)
66.0
± 8.0
(34)
65.4
± 6.4
(36)
61.5
± 7.0
(35)
soy formula
76.5 ± 7.9 (27)
67.7
± 7.3
(31)
59.1
± 6.5
(28)
61.7
± 6.4
(30)
other
24.4 ± 7.9 (11)
29.9
± 15.2
(5)
18.0
± 4.3
(9)
18.3
± 3.3
(11)
(mL/kg)
First
24-h
(mL/kg)
First
24-h
(mL/kg)
Total intake
ing illness
Total intake
ness
fluids
treatment
solution
(mL/kg)
soy formula during
dun-
111.3
± 16.6
(32)
102.6
± 15.2
(34)
135.1
± 18.1
(36)
121.6
± 16.4
(35)
ill-
120.5 ± 21.0
(27)
144.9
± 26.1
(30)
113.8
± 17.2
(30)
116.7
± 12.6
(29)
other
ill-
43.4 ± 15.5
(14)
42.0
± 12.1
(9)
41.3
± 11.6
(16)
(mL/kg)
Total
intake
ness
fluids
during
First 24-h intaket
sodium (ORS)
(mmol/kg)
Total intake
sodium (ORS)1
during
5
38.2
± 8.5
(10)
(mL/kg)
illness
(mmol/kg)
Values
are means
± SE.
6.1 ± 0.7 (34)
10.4 ± 1.5 (32)
Number
of patients
is shown
3.3
± 0.4
(34)
2.0 ± 0.2
(36)
1.8 ± 0.2
(35)
5.0 ± 0.7
(34)
4.1
(36)
3.6
(35)
in parentheses.
± 0.5
Abbreviation
used
is: ORS,
± 0.5
oral
rehydration
solution.
t
P
:1:P
.001 difference
.006 difference
<
=
were
data
group
A and groups
B, C, and D; and between
Duration
of Diarrhea
and Weight
Gain
for Fou r Groups
Group
Duration
of diarrhea
(days) after
treatment
started
% Weight gain 24 h after therapy
started
% Weight
% Weight
gain
at end
of illness
with
well
A
B and groups
C and D.
not all infants
B
Group
(N
1.9 ± 0.2 (32)
1.8 ± 0.2
(34)t
1.0 ± 0.4 (34)
0.8
± 0.5
(33)
-0.2
1.4 ± 0.4
1.1 ± 0.5
2.6 ± 0.7
(29)
(27)
-0.1
4.5
(32)
category
(and
of Patients5
Group
(N = 34)
4.3 ± 0.8 (31)
gain at 2-wk follow-up
compared
group
between
group
A and groups
B, C, and D. The “N” of some variables
differ:
(a)
and/or
other
fluids
by the parent;
(b) data of admitted
patients
were not used in “total”
receiving
<24-h
treatment
not used in 24-h categories).
given
soy
for patients
TABLE 6.
between
= 35)
(N
C
Group
= 36)
(N
D
= 35)
(36)
1.9 ± 0.2
(35)
± 0.3
(34)
0.6
± 0.3
(35)
± 0.4
± 0.7
(34)
(29)
0.9 ± 0.4
3.2 ± 0.7
(33)
(28)
2.0 ± 0.2
weight
S Values
are means ± SE. Number
of patients
is shown in parentheses.
weight data in a given category are not used if one of two paired weights
t Patients
hospitalized
not included in the “N”.
:1:P = .042 difference
between group A and group C only.
The “N” of some
is missing.
variables
differ
because
initial
or follow-up
visits. There
were no differences
in the mean
serum
electrolyte
values
between
the
groups
(data
not shown).
The mean
serum
bicarbonate
values
were also similar
between
the groups
at each of the follow-up
visits.
No differences
were
found
in the mean
bicarbonate
values
between
group A (patients
who were given bicarbonate-con-
hospitalized
during
the study: two at Baltimore
and
one at Whiteniver.
The patients
in Baltimore
were hospitalized
after
36 and 18 hours
of treatment,
respectively,
by the
patients’
private
physicians
because
the infants
were
vomiting
during
therapy.
These
patients
were
taming
domly
three
oral
groups,
solutions.
values
mmol/L
±
2.4,
groups
Treatment
the
rehydration
which
However,
solution)
were
the
given
mean
and
the
other
Both
citrate-containing
serum
bicarbonate
resolution
of illness
were less than
20
in all groups
(17.9 ± 3.0, 16.6 ± 3.2, 16.3
and 17.6 ± 3.4 mmol/L
[mean
± SE]
in
A, B, C, and D, respectively).
at
treatment
however,
failures
three
according
patients
to
were
18
months
and
assigned
had
to
normal
hospitalization;
to have slight
on admission
the
and
A and
they
B,
electrolyte
were
levels
at
The
18-month-old
of dehydration
at the
9-month-old
ran-
respectively.
infant
the
infant
time of
continued
loss of skin turgor
(which was present
to the study),
but had no other clinical
of dehydration
of body weight
The patient
3 months
and
9 months,
groups
serum
time of hospitalization.
had no clinical
signs
signs
Failures
There
were no
study
criteria;
aged
and
had
lost
an additional
from the initial
weight.
hospitalized
at Whiteniver
was randomly
assigned
1%
was aged
to group
A.
ARTICLES
Downloaded from www.aappublications.org/news at Indonesia:AAP Sponsored on July 23, 2021
163
This
patient
was
assessed
to have
at the time of admission
to have diarrhea
during
5%
markedly
dehydration
with
mulas
to the study.
He continued
the first 96 hours
of therapy
during
the
use
of lactose-containing
diarrheal
illnesses.
the
world,
dilutions
at home,
but had no clinical
signs of dehydration.
At the 96-hour
visit,
he was found
to have
no
clinical
signs of dehydration
and had normal
serum
this
phase
of therapy;
able evaluating
We felt that
its use during
it was reasonable
electrolyte
from
patients
treated
and
D
On
values
physical
severe
but
refused
monilial
membrane.
the
oral
he
infection
a nasogastnic
monilial
hours.
None
the
fluids.
to
have
phases
mucosal
hospitalized,
and
was
continued
The
resolved
oral
found
buccal
he was
solution
drip.
infection
drink
was
of
At this time
nehydration
through
to
examination,
diarrhea
within
and
the
48
of
these
three
patients
in the stool;
for rotavirus
had
a recognized
however,
in one
was done.
patient,
only
DISCUSSION
This
(98%)
study
children
demonstrated
were treated
to the study
protocol
plications
occurred
and
in any
34 patients
with
treated
containing
that
137
successfully
diarrhea
rehydration
to be
children
solution
dehydration.
concerned
US
about
pernatremia
being
dration
solutions
United
States,
does
not
is administered
important
an additional
to the child.
water,
breast
feeding.
that
if either
with
treating
this
present
formula
provide
during
therapy
it does
not
sodium
content
study,
for
an
we
the
alternated
with
oral
contain
is minimal
164
ORAL
that
and
(13
a soy-
reasons:
source
(1)
solutions;
(3)
mEqJL),
Elimination
as lactose
REHYDRATION
output
it
(2)
because
its
it would
of lactose
intolerance
more
than
70%
of
Some
investigators’4
stool
in
to
of nutrients
rehydration
lactose;
reported
in
from diarrhea.’3
demonstrated
B,
solutions
We chose
following
additional
act as a source
of free water.
was thought
to be desirable
has been
suffering
patients
source
of free water should
be offered
This
may be done
by offering
free
milk, or some other form of low-solute
In the
would
is
A and
based
formula
with oral rehydration
children
less than
12 months
of age.
use
It
solutions
also
FOR ACUTE
few
first
together
because
between
patients
data
of
during
are
avail-
(solutions
polymer)
all the admission
characteristics
ables that were analyzed.
Patients
in group A ingested
as the
used
diarrheal
illness.
to present
the data
glucose
differences
B,
and
there
were
the
two
and
outcome
three
in groups
no
phases
times
C and
C,
second
in
vanas much
D. In spite
of being exposed
to a relatively
“high”
sodium
load,
hypernatremia
was not seen in any of the patients.
As demonstrated
in our previous
study among
hospitalized
patients,’
the excess sodium
was undoubtedly excreted
in the urine.
We have previously
demonstrated’
that hospitalized US children
can be treated
with oral rehydration
solutions
containing
90
or
50
mmol/L
of so-
This
study
infants
have
increases
DIARRHEA
also
demonstrates
that
citrate-based
oral rehydration
solutions
are as efficacious
as the
bicarbonate-based
oral
rehydration
solutions
in
correcting
mild acidosis.
Because
citrate
is more
stable than bicarbonate,
citrate-based
oral nehydration solutions
can be stored
and dispensed
in the
solution
form.
Furthermore,
this study
also demonstrates
that
the 2% glucose
polymer
used in the first part of the
Baltimore
of these
recommended.’
while
dehydration
study
conchildren
we demonstrated
occur
as
to recognize
minimal
of hy-
The
present
in hospitalized
in which
hypernatremia
solutions
con-
possibility
by the use of oral rehy90 or 50 mmol/L
of
sodium
in US children.6’7
firms
our previous
findings
in the
minimal
pediatricians
the
induced
containing
with
study
the
are
areas
dium even if they are initially
seen with mild hypernatremia.
Recent
studies
in Costa
Rica’5 have
confirmed
these
findings
in hospitalized
patients
with moderate-to-severe
hypernatremia.
com(including
of sodium).
ambulatory
and
tinue
with
the
140
according
present
study
was specifically
designed
to
the safety
and efficacy
of four oral rehysolutions
of differing
sodium
concentrain treating
that
of
no therapy-related
of the groups
oral
90 mmol/L
The
evaluate
dration
tions
of the
sodium
pathogen
the assay
in
for-
many
milk
however,
contained
significant
the
next
of cow’s
In
study
omenic
The
glucose
present
lutions
tested
was
equally
as
efficacious
as
at the same concentration.
study demonstrates
that
are
equally
effective
and
mon-
all the
safe
so-
in treat-
ing US patients
with mild diarrhea.
The commercial solutions
that have been commonly
used in the
past for ambulatory
US children
initially
seen with
diarrhea
contain
30 mmol/L
of sodium
and 5% to
8% glucose.
The sodium
content
in the latter
solutions
and in solutions
C and D used
in the present
study
is not
adequate
moderate-to-severe
use
of these
for treatment
diarrhea
solutions
may
of patients
because
lead
with
the prolonged
to hyponatremia.’6
An additional
disadvantage
with
the commonly
used commercial
oral rehydration
solutions
is their
high glucose
content.
It has been shown
that
in
order to obtain
optimal
water
and sodium
absorption from the gut, a solution
containing
1 10 to 140
mmol/L
of glucose
(approximately
2% to 2.5%)
should
be used.’7
If glucose
absorption
is incomplete,
solutions
containing
5% to 8% glucose
will
create
a high
osmotic
load
in the
Downloaded from www.aappublications.org/news at Indonesia:AAP Sponsored on July 23, 2021
gut
and
interfere
with absorption
of water,
possibly
leading
to osmotic diarrhea
and the development
of hypernatremia. This phenomenon
was observed
in a recent
clinical
study by Mahalanabis
and Patra’8
in which
carbonate-based
ing ambulatory
they
compared
a solution
containing
glucose
with a solution
containing
20 g/L
ACKNOWLEDGMENTS
The study
was
marked
increase
40 g/L
prematurely
in diarrhea
of glucose.
seven
terminated
in the group
In addition,
isonatremic
40 g/L
of
of glucose.
patients
Sandhu
with
due to
receiving
a
et al treated
an oral
rehydration
of a glucose
polymer.
had an increase
of
serum
greater
sodium
concentration
than
3 mmol/
L after 48 hours of therapy.
In one of these patients,
the serum
sodium
concentration
rose to 162 mmol/
L.’9 Physiologic
studies
of absorption
of water and
sodium
from
the
gut
in relationship
to glucose
polymer
concentrations
of
oral
solutions
are
not
available.
Two
ent
patients
study
infants
by
each
thought
to
the time of
infant
had
We believe
were
their
hospitalized
private
vomited
two
the
during
physicians
times.
One
resolved
their
diarrhea
the
infant
was
without
rehydration
therapy.
On
the
contrary,
we
have
shown
among
US children’
and others
have shown
in a number
of developing
countries2’3
that
the
majority
of children
initially
seen with vomiting
can be rehydrated
with oral rehydration
therapy
provided
the rehydration
solution
is offered in small
volumes.
One
to
infant
take
oral
infection.
States,
was hospitalized
fluids
due
In our anecdotal
we
have
administered
to
because
a severe
experience
oral
of his refusal
oral
monilial
in the United
rehydration
so-
lutions
through
a nasogastnic
tube in a number
of
patients
who have refused
oral intake
due to monilial infection
of the buccal
mucosal
membrane.
This
infection
tially
offers
seen
an
is occasionally
seen
in children
with
diarrhea,
and the nasogastnic
alternate
method
of administering
Witzke
by National
Institutes
of Health
grant
Pediatric/Medical
Clinic,
and the Comprehensive
Child Care Clinic of the Johns
Hopkins
Hospital,
Baltimore, and the medical
and nursing
staff of the US Public
Health
Service
Indian
Hospital,
Whiteriver,
Arizona.
We
also thank
Andrea
Lee for secretarial
help, and Leslie
Benson
and Jean Froehlich
for technical
help.
REFERENCES
1.
mitube
oral
rehydration
solutions
to such
children.
We only
recommend
this method
of hydration
in hospitalized children.
We conclude
that (1) this study
supports
recent
recommendations8
that oral rehydration
solutions
containing
90 or 50 mmol/L
of sodium
can be used
safely to hydrate
both hospitalized
and ambulatory
children
in the United
States
and (2) citrate-based
oral rehydration
solutions
are as efficacious
as bi-
Santosham
M, Daum
therapy of infantile
nourished
children
RS, Dillman
diarrhea:
hospitalized
L, et al: Oral rehydration
study of wellin the United
States
and
A controlled
Panama.
N Engl J Med
1982;306:1070-1076
2. Hirschhorn
N: The treatment
of acute diarrhea
An historical
and physiological
perspective.
Am
com-
plications
if they
had been
allowed
to continue
therapy
on the study
protocol.
These
two cases
serve to illustrate
a common
belief among
US pediatnicians,
ie, vomiting
is a contraindication
for
oral
sponsored
#5M01RR35-20.
The authors
thank
the physicians
and nursing
staff of
the Pediatric
Clinic
of the Francis
Scott
Key Medical
Center
(formerly
Baltimore
City Hospital),
the Albert
pres-
because
have no clinical
signs of dehydration
at
admission
to the hospital
and the other
not yet completed
24 hours
of therapy.
that both of these patients
would have
successfully
in treatdiarrhea.
This work was supported
by a grant
from the Wyeth
Laboratories
and National
Institutes
of Health,
National
Institute
of Allergy
and Infectious
Diseases
Contract
No.
NO1-AI-02660.
Computational
assistance
was received
from CLIN.
FLO,
solution
containing
125 g/L
Four
of these
seven
patients
oral rehydration
solutions
patients
with mild acute
in children:
J Clin Nutr
1980;33:637-663
3. Population
Reports:
Oral
Rehydration
Therapy
(ORT) for
Childhood
Diarrhea
(series L44-75,
no 2). Baltimore,
Population
Information
Program,
The Johns
Hopkins
University, Nov-Dec
1980
4. Chatterjee
A, Mahalanabis
D, Jalan
KN, et al: Oral rehydration in infantile
diarrhea:
Controlled
trial of low sodium
glucose electrolyte
solution.
Arch Dis Child 1978;53:284-289
5. Santosham
M, Carrera
E, Sack RB: Oral rehydration
therapy in well nourished
ambulatory
patients.
Am J Trop Med
Hyg 1983;32:804-808
6.
Walker
SH: Hypernatremia
from oral electrolyte
solutions
in infantile
7. Bart KJ,
diarrhea,
letter. N EngI J Med 1981;304:1238
Finberg
L: Single
solution
for oral therapy
of
diarrhea,
letter. Lancet 1976;2:633-634
8. Finberg
L, Harper
PA, Harrison
HE, et al: Oral rehydration
for diarrhea.
J Pediatr
1982;101:497-499
9. Carpenter
CCJ: Oral rehydration:
Is it as good as parenteral
therapy?
N EngI J Med
1982;306:1103-1104
10. National
Center
for Health
Statistics:
NCHS
Growth Curves
for Children
Birth-18
Years,
United
States,
US Dept of
Health,
DHEW
Education
and
Welfare,
publication
No.
(PHS)
Public
78-1650,
Health
Hyattsville,
Service,
MD,
1977
11. Yolken
RH, Wyatt
RG, Zissis G, et al: Epidemiology
of
human
rotavirus
types 1 and 2 as studied
by enzyme-linked
immunosorbent
assay. N EnglJ
Med
1978;299:1156-1161
12. Santosham
M, Sack RB, Froehlich
J, et al: Biweekly
prophylactic
doxycycline
for travelers’
diarrhea.
J Infect Dis
1981;143:598-602
13. Lifshitz
F, Coello-Ramircz
Carbohydrate
intolerance
P, Gutierrez-Topete
in infants
with diarrhea.
G, et al:
J Pediatr
1971;70:760-767
14. Torres-Pinedo
infant diarrhea:
R, Lavastida
M, Rivera CL, et al: Studies
on
I. A comparison
ofthe effects ofmilk
feeding
and intravenous
therapy upon the composition
and volume
of the stool and urine. J Clin Invest
1966;4:469-480
15. Pizarro
D, Posada G, Villavicencio
N, et al: Oral rehydration
in hypernatremic
and hyponatremic
diarrheal
dehydration.
Am J Dis Child 1983;137:730-734
16. Finberg
L: The role of oral electrolyte-glucose
solutions
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165
hydration
for children:
J Pediatr
1980;96:51-54
17. Sladen
GE, Dawson
sorption
jejunum.
18. Mahalanabis
of glucose,
International
and domestic
AM:
Interrelationship
sodium
and water
Clin Sci 1969;36:119-132
D, Patra FC: In search
aspects.
the ab-
between
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of a super
oral
human
19.
optimum
use of organic
lead to the development
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Dis Res
BJM, Brook
1983;1:76-81
CGD, et al: Oral rehydration
T. GRANT
SCHOLARS
FOUNDATION
AWARD
1985
Each year William
T. Grant
Foundation
makes awards
to five young research
workers
in the field of children’s
mental
health.
Institutions
where the scholars
work receive
$150,000,
plus indirect
costs for partial
support
for the scholars
for five years.
The purpose
of the award
is to protect
the research
time of the
scholars
during
the critical
early years of their careers.
Preference
is given to
scholars
working
in the field of the Foundation’s
principal
interest-understanding
how
school-age
children
fulfill their potential.
This year the Foundation
were
made to:
1. Deborah
Psychology,
Belle,
EdD,
Boston
has
Director
cope
chosen
Stress
with
stresses
four
scholars,
and
Families
that
may
and
the
Project,
lead
to failure
awards
to
for 1985
Department
of
University
2. Polly Ellen Bijur, PhD, Associate
Professor,
Department
of Pediatrics,
Albert
Einstein
College
of Medicine
3. Candice
Feiring,
PhD,
Assistant
Professor
of Pediatrics,
Rutgers
Medical
School,
University
of Medicine
and Dentistry
of New Jersey
4. Lonnie
Zeltzer,
MD, Head, Division
of Adolescent
Medicine,
Department
of
Pediatrics,
University
of Texas
Health
Science
Center
The Foundation
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Deadlines
tions are July 1 of each year. Information
on application
procedures
from the Foundation,
919 Third
Aye, New York, NY 10022. (212)
166
solute-mediated
of an absorption
in acute infantile
diarrhoea
with a glucose-polymer
lyte solution.
Arch Dis Child 1982;57:152-160
rehydra-
WILLIAM
FACULTY
tion solution: Can
sodium absorption
promoting
drug? J
Sandhu BK, Jones
for applicais available
752-0071.
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Oral Rehydration Therapy for Acute Diarrhea in Ambulatory Children in the United
States: A Double-Blind Comparison of Four Different Solutions
Mathuram Santosham, Barbara Burns, Vinay Nadkarni, Stephan Foster, Steven Garrett,
Larry Croll, J. Crosson O'Donovan, Radha Pathak and R. Bradley Sack
Pediatrics 1985;76;159
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Oral Rehydration Therapy for Acute Diarrhea in Ambulatory Children in the United
States: A Double-Blind Comparison of Four Different Solutions
Mathuram Santosham, Barbara Burns, Vinay Nadkarni, Stephan Foster, Steven Garrett,
Larry Croll, J. Crosson O'Donovan, Radha Pathak and R. Bradley Sack
Pediatrics 1985;76;159
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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has
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American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1985 by the
American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.
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