1. health and fitness
2. disease
3. ibs and crohn's disease

Dose response of PEG 3350 for the treatment of
childhood fecal impaction
Nader N. Youssef, MD, John M. Peters, DO, Wendy Henderson, CRNP, Sandra Shultz-Peters, CRNP,
Danielle K. Lockhart, CRNP, and Carlo Di Lorenzo, MD
Objective: To investigate the efficacy and safety of polyethylene glycol
(PEG) 3350 in the treatment of childhood fecal impaction.
Methods: This was a prospective, double-blind, parallel, randomized study
of 4 doses of PEG 3350; 0.25 g/kg per day, 0.5 g/kg per day, 1 g/kg per day,
1.5 g/kg per day, given for 3 days in children with constipation for >3 months
and evidence of fecal impaction.
Results: Forty patients completed the study (27 boys, median age 7.5, range
3.3-13.1 years). Disimpaction occurred in 75% of children, with a significant
difference between the two higher doses and the lower doses (95% vs 55%,
P < .005). All groups had an increased number of bowel movements during
the 5-day study versus baseline, respectively: 6.5 versus 1.1 (P < .005), 8.0
versus 1.3 (P < .005), 10.9 versus 1.7 (P < .005), and 12.3 versus 1.4
(P < .005). Adverse effects included nausea (5%), vomiting (5%), bloating
(18%), cramping (5%), and diarrhea (13%). Diarrhea and bloating were
more prevalent (P < .02) in the higher-dose than in the lower-dose group.
No clinically significant changes in electrolytes were noted.
Conclusions: The 3-day administration of PEG 3350 is safe and effective in
the treatment of childhood fecal impaction at doses of 1 and 1.5 g/kg per day.
(J Pediatr 2002;141:410-4)
Functional fecal retention is the most
common cause of chronic constipation
and fecal soiling in children.1 In this
condition, there are repetitive attempts
to avoid defecation because of fears of a
painful evacuation. Consequently, a
large fecal mass accumulates in the rectum. The North American Society for
Pediatric Gastroenterology, Hepatology, and Nutrition, in a recently published statement on the evaluation and
treatment of childhood constipation,
suggested that fecal disimpaction is
beneficial before initiation of maintenance therapy.2 Clearance of fecal material may be achieved with oral or
From the Division of Pediatric Gastroenterology, University of Pittsburgh School of Medicine and Children’s Hospital
of Pittsburgh, Pennsylvania.
Supported by Braintree Laboratories Incorporated, General Clinical Research Center, Children’s
Hospital of Pittsburgh, Pittsburgh, Pennsylvania, National Institutes of Health Grant No.
M01RR00084.
Submitted for publication Feb 1, 2002; revisions received Mar 20, 2002 and May 6, 2002; accepted May 15, 2002.
Reprint requests: Nader N. Youssef, MD, 3705 Fifth Ave at DeSoto St, Pittsburgh, PA 15213.
Copyright © 2002, Mosby, Inc. All rights reserved.
0022-3476/2002/$35.00 + 0 9/21/126603
doi:10.1067/mpd.2002.126603
410
rectal agents.3-5 There is often reluctance by parents and children to use
oral agents such as mineral oil, polyethylene glycol electrolyte solutions
(PEG-ELS), and magnesium citrate
secondary to poor palatability, nausea,
and cramping. Enemas using phosphate
soda, saline, and mineral oil solutions
are commonly used and appear to be effective.3 Unfortunately, repeated administration of enemas is strongly
disliked by children and often leads to
use of inadequate doses and failure of
treatment.
PEG
Polyethylene glycol
Polyethylene glycol solution (PEG)
3350 without added electrolytes (MiraLax, Braintree Labs, Braintree,
Mass) is a newly developed, flavorless
and odorless osmotic laxative in powder
form that is absorbed only in trace
amounts from the gastrointestinal
tract.6 To date, it has been approved by
the Food and Drug Administration for
the treatment of chronic constipation
only in adults.7 Unlike other colonic
lavage solutions, there is no risk for salt
absorption.8 The effective dose of PEG
3350 for maintenance treatment of
childhood constipation has recently
been reported.9 PEG 3350 as an oral
agent in the clearance of fecal impaction
before maintenance treatment has not
been studied in children.
METHODS
Design
The study was designed to test the efficacy and safety of 4 different doses of
PEG 3350 in the treatment of fecal
YOUSSEF ET AL
THE JOURNAL OF PEDIATRICS
VOLUME 141, NUMBER 3
impaction in children. The design was
a prospective, double-blind, parallel
study. Patients enrolled were children
examined in the pediatric gastroenterology clinic with complaints of chronic
constipation and/or soiling and who had
a fecal impaction. The primary outcome
measure of the study was clearance of
fecal impaction. Presence or absence of
fecal impaction was assessed by abdominal and rectal examination. Secondary
outcome measures included number of
bowel movements during the study versus baseline. In addition, we evaluated
characteristics of stools in the 4 different dose groups as measured by diaries
provided to the parents. Safety was
measured by laboratory evaluation of
sodium, potassium, chloride, bicarbonate, magnesium, phosphorous, calcium,
blood urea nitrogen, creatinine, and
serum osmolarity, checked before and
after treatment.
Study Population
Only new patients referred to the pediatric gastroenterology clinic for evaluation of constipation with evidence of
fecal impaction were enrolled into the
study. Patients initially underwent a
telephone screen to evaluate the presence of functional fecal retention as defined by the Rome criteria.10 These
criteria include difficulty passing stools
>3 months (straining, grunting, stool
“getting stuck”) and passage of stools <3
times per week.
Inclusion Criteria
Eligible children for the study were
those 3 to 18 years of age, male or female, with no previous gastrointestinal
surgery, no allergy/sensitivity to PEG
solution or phosphates, and willing to
participate in the study. All medications
for constipation had to be discontinued
7 days before examination. All children
had to have evidence of a fecal impaction defined as a palpable mass in
the left lower abdomen and/or a dilated
rectum filled with a large amount of
hard stool on rectal examination. No
patient was enrolled that had signs and
Fig 1. Disimpaction response by dose. *P < .005, 1.0 and 1.5 g/kg per day versus 0.25 and 0.5 g/kg
per day.
symptoms suggestive of obstruction;
this included vomiting, abdominal distension, and an abdominal mass that
extended beyond the level of the umbilicus. Physical examinations were preformed by two examiners to confirm
presence of the fecal impaction. We
planned to enroll 10 children in each of
4 dose groups.
Baseline Visit
At this visit, an informed consent was
obtained from parents and assent from
children. The initial visit included history, complete physical exam, and assessment of constipation and bowel habits
by a scoring system previously used in
constipated adults11 (Table available at
www.mosby.com/jpeds). The scoring
system was used as a tool for evaluation
to help quantify historic data as reported by parents and not as a measure of
severity of constipation. Diaries aimed
at assessing stool characteristics and
monitoring symptoms during the study
were distributed. The diaries had visual
analog scales marked from 0 to 10; each
mark evenly spaced 1 cm apart, where
0 was the minimum and 10 was the
maximum. In the diaries, children and
their parents were asked to report each
defecation and its associated straining
(0, very easy and no pushing; 1-10, very
difficult and much effort), consistency
of stool (0, too loose and watery; 1-10,
very hard), amount of stool per defecation (0, very little; 1-10, a lot), associated gas (0, none; 1-10, too much), and
cramping (0, none; 1-10, very painful).
Random Assignment
Once entry criteria were met, patients
were randomly assigned to receive PEG
3350 in 1 of 4 doses, 0.25 g/kg per day,
0.5 g/kg per day, 1 g/kg per day, or 1.5
g/kg per day for 3 consecutive days.
The maximum dose was 100 g daily. All
medications were dispensed to families
premixed in a solution flavored in orange Crystal Light (Kraft Foods, Inc,
Northfield, Ill) in a clear container labeled with only a random sequence
number generated by the manufacturer.
All containers initially contained PEG
3350: 50 g, 100 g, 200 g, or 300 g. Each
container was then constituted to a
2000-mL solution for respective doses
of 0.025 g/mL, 0.05 g/mL, 0.1 g/mL, or
0.15 g/mL. Patients then received a
dose of 10 mL/kg per day. Patients were
given written instructions on the daily
amount to be taken and provided with
measuring cups. All patients were instructed to take the medication in the
morning with breakfast. If the volume
exceeded 240 mL, the remaining daily
dose was equally divided throughout
the remaining meals. Investigators were
blinded to the randomization allocation
sequence and its concealment was
411
YOUSSEF ET AL
THE JOURNAL OF PEDIATRICS
SEPTEMBER 2002
Table I. Patient data and constipation score
Age (y)
Sex (male)
Weight (kg)
Duration (mo)
Previous medication (%)
Constipation score‡
0.25 g/kg/day
(n = 10)
0.5 g/kg/day
(n = 10)
1 g/kg/day
(n = 10)
1.5 g/kg/day
(n = 10)
7.98 ± 2.5
7
27.3 ± 10.3
36 ± 28
50
10.7 ± 2.6
5.7 ± 1.72*
7
25.7 ± 15.4
33.8 ± 26.2†
70
13 ± 3.7
7.8 ± 2.9
8
26.8 ± 10.6
48.3 ± 24.3
20
9.4 ± 2.7
8.6 ± 2.9
7
37.9 ± 20.1
42 ± 33.2
50
11.5 ± 3.9
*P < .03 versus 1.5 g/kg/day.
†P < .04 versus 1 g/kg per day.
‡See Table III, available at www.mosby.com/jpeds.
Table II. Stool characteristics and symptoms during treatment
PEG 3350 dose
Straining
Consistency
Stool amount
Gas
Cramping
0.25 g/kg/day
0.5 g/kg/day
1.0 g/kg/day
1.5 g/kg/day
3.1 ± 2.0
4.8 ± 2.2
4.7 ± 2.3
1.8 ± 1.7
1.0 ± 0.7
4.2 ± 3.1
5.6 ± 3.1
3.9 ± 2.5
1.3 ± 0.9
2.4 ± 2.8
2.6 ± 0.7
3.3 ± 0.4
4.1 ± 1.6
1.7 ± 0.7
1.0 ± .37
1.6 + 1.1
2.5 + 1.4
4.2 + 1.7
1.2 + 1.1
0.7 + 1.0
Scores described in Methods section. No significant difference was found in any of the parameters among the 4 groups.
maintained until all patients enrolled
completed the study and all data had
been collected. Patients had access to a
physician 24 hours a day during the
study. All other medications used for
the treatment of constipation had to be
discontinued during the study.
lower quadrant mass in addition to an
empty rectal vault was defined as a successful disimpaction. Clearance of fecal
impaction was confirmed by two examiners. The same laboratory evaluation
performed at enrollment was repeated.
The Human Rights Committee at the
Children’s Hospital of Pittsburgh approved the study.
Follow-up Visit
Data Analysis and
Interpretation
Patients were examined on the 5th
day after starting treatment, 48 hours
after their last drug dose, to assess outcome of disimpaction, record adverse
events, and collect bowel diaries and
medication containers. The 5th day
after initiation of treatment was chosen
because of our previous clinical experience with PEG 3350, which showed an
initial effect between 1 and 2 days after
beginning the use of the medication.
Clearance of fecal impaction was defined as a rectal vault that was either
empty or had a small amount of soft
stools. In those with abdominal examination findings, resolution of the left
In the analysis, only patients who
completed the 3-day treatment and returned for follow-up were considered.
For all analyses, an effective treatment
was defined as clearance of the impaction. Analysis of variance was used
to compare continuous outcomes, and
the χ2 test was used to compare categoric outcomes. We used the Student t
test for paired samples to calculate
P values related to laboratory evaluation. The comparison was with values
before the start of therapy. All
P values are 2-sided, with P value < .05
being considered as statistically
significant.
Forty-one children fulfilled the inclusion criteria; 40 children (27 male, median age 7.5, range 3.3-13.1 years)
completed the study. One child receiving a dose of 1.5 g/kg per day did not
show up at the follow-up visit. Overflow fecal soiling occurred in 35 children, with 91% having it daily.
Associated symptoms included straining (90%), hard consistency stools
(85%), feeling of incomplete evacuation
(55%), feeling of blockage (40%), and
defecation only achieved using manual
maneuvers such as suppositories or enemas (13%).
Baseline patient characteristics and
constipation scores in the different dose
groups are summarized in Table I. At
412
RESULTS
YOUSSEF ET AL
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VOLUME 141, NUMBER 3
the time of evaluation, 41 patients had
evidence of large amount of hard stool
in the rectal vault; 28 of these patients
(distributed through all groups) also
had evidence of a left lower abdominal
mass. Twenty-three patients (58%) were
receiving no medications for constipation at time of evaluation. The mean duration of symptoms of constipation was
39.6 months (range 6-120 months).
Primary Outcome
At follow-up, disimpaction had been
achieved in 30 children (75%). Three of
10 patients whose fecal impaction had
not cleared on digital rectal examination
also had persistent abdominal left lower
quadrant fecal mass. There was a significant difference between higher doses
(1 and 1.5 g/kg/day) and lower doses
(0.25 and 0.5 g/kg/day) in the rate of
disimpaction (95% vs 55%, P < .005).
Results in each subgroup are shown in
Fig 1. Success of disimpaction was not
significantly related to the independent
factors of age, duration of constipation,
current use of medications for constipation, and baseline constipation score.
Secondary Outcomes
Thirty-three children (83%) had >3
bowel movements during the 5-day
study. All doses used led to an increase
in the number of stools (Fig 2). It took
a mean of 1.89 ± 0.46 days for patients
to have their first bowel movement
after initiation of treatment. Stool characteristics and associated symptoms in
the 4 dose groups during the treatment
are reported in Table II. A trend for
defecations to be associated with less
straining and looser consistency was
noted with increasing doses, with no
statistical significance noted between
the dose groups in any of the stool
characteristics.
Adverse events included nausea
(5%), vomiting (5%), bloating/flatulence (18%), pain/cramping (5%), and
loose stools (13%). Diarrhea was more
prevalent (P < .02) in the higher dose
groups (5 of 20 patients) versus the
lower doses (2 of 20 patients). No pa-
Fig 2. Number of bowel movements during treatment versus baseline.
tient had clinically significant abnormal laboratory values after the use of
PEG 3350. Statistical significance was
found in serum calcium in the 0.25
g/kg per day group (9.7 mg/dL after
treatment vs 9.5 mg/dL before treatment, P < .02).
Parents were polled about the acceptance of study medication by their children; 95% of children took PEG 3350
on the first attempt. There were no statistical differences in the mean daily volumes required to take the appropriate
study dose between groups: (1) 273 ±
103 mL (range, 140-665 mL); (2) 257 ±
154 mL (range, 150-665 mL); (3) 268 ±
106 mL (range, 170-480 mL); and (4)
379 ± 201 mL (range, 130-620 mL), respectively. All children said that they
would repeat a 3-day regimen of PEG
3350 to help treat a future fecal impaction.
DISCUSSION
In this prospective, double-blind, parallel study we found that children with
fecal impaction can be treated effectively and safely with PEG 3350. Doses of
1.0 and 1.5 g/kg per day for 3 days were
more effective than lower doses, regardless of age of patients, duration of symptoms, or severity of constipation. The
effective doses can be administered in
relatively small daily volumes.
The use of PEG-ELS–based solutions has become increasingly popular
in the treatment of childhood constipation.3,4 The main advantage of PEG
3350 is that it is virtually tasteless and
odorless when mixed in solution.7 Studies in adults receiving PEG 3350
showed a significant increase in weekly
bowel movement frequency and significant decrease in straining, stool consistency, and laxative use.7 A recent
open-label study using PEG 3350 in the
treatment of childhood chronic constipation showed an increase in weekly
stool frequency, decrease in stool consistency, and decline in weekly soiling
events.9 As in our study, Pashankar et
al9 required higher than the manufacturers recommended dose of 17 grams
daily, reporting that a dose of 0.8 g/kg
per day was needed for children to
evacuate 2 soft stools per day. In this
study, doses up to 36 g of PEG 3350 diluted in 8 ounces of fluid were used over
a short term to achieve fecal disimpaction and appeared to be well tolerated without disturbing electrolytes and
osmolarity.
In our series, >85% of children had
episodes of overflow soiling, a common
consequence of functional fecal retention. When defecation is delayed purposefully secondary to fear of a painful
evacuation, there is an accumulation of
hard, difficult-to-pass feces in the rectum, and if not cleared, liquid stools will
413
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THE JOURNAL OF PEDIATRICS
SEPTEMBER 2002
begin leak around the rectal mass with
negative emotional impact on the child.
Frequently, stool retention begins at the
time of toilet training, when toddlers
may refuse to use the potty because of
excessive parental pressure, inappropriate timing, or the decision to “exercise
their will.”12 The findings of this study
confirm that toilet training is a critical
time in the onset of childhood constipation, in view of the mean age of the study
patients being 7.5 years with a mean duration of symptoms of over 3 years.
Since the clinical presentation of constipation is variable, a scoring system
was used at time of the initial visit. The
scoring system has been used by other
investigators in adult patients to help
standardize evaluation.11 We used the
system to quantify historic data as reported by children’s parents and not to
grade the severity of constipation. The
baseline constipation score was not significantly different among the four different dose groups and did not predict
those who were successfully disimpacted or those who had more bowel movements, suggesting that adequate doses
of PEG 3350 may be effective even in
the most severe cases of fecal impaction.
Adverse effects related to PEG 3350
were related mostly to its osmotic laxative effect. Families judged side effects
as minor and acceptable. Adverse
events included nausea, vomiting, bloating and increased flatulence, and abdominal cramping. Bloating and
increased flatulence were seen mostly in
the higher doses. It is questionable if
loose stools in the treatment of consti-
pation should be considered a success
or an adverse effect since 95% of children on the higher doses were successfully disimpacted safely.
In conclusion, this study demonstrates that fecal impaction in children
can be treated effectively by PEG
3350. Patients with signs and symptoms suggestive of a fecaloma and possible obstruction such as vomiting,
abdominal distension, and abdominal
fecal mass that extended beyond the
level of the umbilicus were not studied. The most likely mechanism of success of disimpaction is due to the
osmotic and stool softening effect of
PEG 3350. This leads to more bowel
movements that are easier to pass. The
most effective doses in this study were
in the range of 1.0 to 1.5 g/kg per day
with a maximum daily dose of 100 g
given for 3 consecutive days. It is likely that PEG 3350 will become the
agent of choice in treating childhood
constipation during both disimpaction
and maintenance phases of treatment
because of its effectiveness and patient
acceptance.
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Brady CE III, DiPalma JA, Morawski SG,
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You can find additional data from this study by logging onto
The Journal of Pediatrics Online at www.mosby.com/jpeds.
414
Table III. Constipation scoring system
Score
Frequency of bowel movements
1–2 times/1–2 d
2 times/wk
1 time/wk
1 time/wk
1 time/mo
Difficulty: painful evacuation
Never
Rarely
Sometimes
Usually
Always
Completeness: feeling of incomplete evacuation
Never
Rarely
Sometimes
Usually
Always
Pain: abdominal pain
Never
Rarely
Sometimes
Usually
Always
Time: minutes in bathroom per attempt
5
5–10
10–20
20–30
>30
Assistance: type of assistance
Without assistance
Stimulative laxatives
Digital assistance or enema
Failure: unsuccessful attempts for evacuation/24 h
Never
1–3
3–6
6–9
>9
History: duration of constipation (y)
0
1–5
5–10
10–20
>20
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
0
1
2
3
4
0
1
2
3
4