ARTICLE

Bowel Preparations for Colonoscopy: An RCT

AUTHORS: Giovanni Di Nardo, MD, PhD,a Marina Aloi, MD,
PhD,a Salvatore Cucchiara, MD, PhD,a Cristiano Spada,
MD,b Cesare Hassan, MD,b Fortunata Civitelli, MD,a
Federica Nuti, MD, PhD,a Chiara Ziparo, MD,a Andrea
Pession, MD, PhD,c Mario Lima, MD, PhD,d Giuseppe La
Torre, MD, PhD,e and Salvatore Oliva, MDa

WHATS KNOWN ON THIS SUBJECT: Available bowel preparation

solutions for colonoscopy continue to represent a challenge for
children and their families due to poor taste, high volume, and
dietary restrictions with subsequent poor compliance and need to
place nasogastric tube for administration.

Departments of aPediatrics, Pediatric Gastroenterology Unit, and

ePublic Health and Infectious Diseases, Sapienza University of
Rome, Rome, Italy; bDigestive Endoscopy Unit, Universit Cattolica
del Sacro Cuore, Rome, Italy; and Departments of cPaediatrics,
Pediatric Gastroenterology and Nutrition Unit, and dPediatric
Surgery, S. Orsola-Malpighi Hospital, University of Bologna,
Bologna, Italy

WHAT THIS STUDY ADDS: Low-volume polyethylene glycol (PEG)

preparations and sodium picosulphate plus magnesium oxide and
citric acid (NaPico+MgCit) are noninferior to PEG 4000 with
simethicon for bowel preparation before colonoscopy in children.
Given its higher tolerability and acceptability prole, NaPico+MgCit
should be preferred in children.

KEY WORDS
colonoscopy, colon cleansing, children
ABBREVIATIONS
BBPSBoston Bowel Preparation scale
CIcondence interval
NaPico+MgCitsodium picosulphate plus magnesium oxide and
citric acid
PEGpolyethylene glycol
PEG-Ascpolyethylene glycol 3350 with ascorbic acid
PEG-CSpolyethylene glycol 4000 with citrates
PEG-ELSpolyethylene glycol 4000 with simethicon
Drs Di Nardo and Oliva conceptualized and designed the study,
performed endoscopy, drafted the initial manuscript; Drs Aloi,
Civitelli, Nuti, and Ziparo conceptualized and designed the study
and enrolled and followed-up patients; Drs Hassan, Spada,
Pession, and Lima conceptualized and designed the study and
contributed signicantly to the nal revision of the manuscript;
Dr La Torre carried out the statistical analyses and reviewed
and revised the manuscript; Dr Cucchiara is the head of the
Pediatric Gastroenterology Unit, performed endoscopy and
reviewed and revised the manuscript; and all authors approved
the nal manuscript as submitted.
This trial has been registered at www.clinicaltrials.gov
(identier NCT01711437).
www.pediatrics.org/cgi/doi/10.1542/peds.2014-0131
doi:10.1542/peds.2014-0131
Accepted for publication May 1, 2014
Address correspondence to Giovanni Di Nardo, Department of
Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza
University of Rome, University Hospital Umberto I, Viale Regina
Elena 324-00161 Rome, Italy. E-mail: giovanni.dinardo@uniroma1.it
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2014 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated
they have no potential conicts of interest to disclose.

abstract
BACKGROUND: The ideal preparation regimen for pediatric colonoscopy
remains elusive, and available preparations continue to represent a challenge for children. The aim of this study was to compare the efcacy,
safety, tolerability, and acceptance of 4 methods of bowel cleansing before
colonoscopy in children.
METHODS: This randomized, investigator-blinded, noninferiority trial
enrolled all children aged 2 to 18 years undergoing elective colonoscopy
in a referral center for pediatric gastroenterology. Patients were randomly
assigned to receive polyethylene glycol (PEG) 4000 with simethicon (PEGELS group) or PEG-4000 with citrates and simethicone plus bisacodyl (PEGCS+Bisacodyl group), or PEG 3350 with ascorbic acid (PEG-Asc group), or
sodium picosulfate plus magnesium oxide and citric acid (NaPico+MgCit
group). Bowel cleansing was evaluated according to the Boston Bowel
Preparation Scale. The primary end point was overall colon cleansing.
Tolerability, acceptability, and compliance were also evaluated.
RESULTS: Two hundred ninety-nine patients were randomly allocated to
the 4 groups. In the per-protocol analysis, PEG-CS+Bisacodyl, PEG-Asc, and
NaPico+MgCit were noninferior to PEG-ELS in bowel-cleansing efcacy of
both the whole colon (P = .910) and colonic segments. No serious adverse
events occurred in any group. Rates of tolerability, acceptability, and
compliance were signicantly higher in the NaPico+MgCit group.
CONCLUSIONS: Low-volume PEG preparations (PEG-CS+Bisacodyl, PEG-Asc)
and NaPico+MgCit are noninferior to PEG-ELS in children, representing an
attractive alternative to high-volume regimens in clinical practice. Because
of the higher tolerability and acceptability prole, NaPico+MgCit would
appear as the most suitable regimen for bowel preparation in children.
Pediatrics 2014;134:249256

PEDIATRICS Volume 134, Number 2, August 2014

249

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Colonoscopy is an established diagnostic

and therapeutic tool in a variety of gastrointestinal tract conditions affecting
children and adolescents. For example, it
is crucial for establishing the diagnosis of
inammatory bowel disease and provides denitive therapeutic options in
patients with colonic polyps or lower
gastrointestinal bleeding.1 The success of
colonoscopy relies on multiple factors,
and bowel preparation is among the
most important of these. Inadequate
bowel cleansing may have negative consequences for the examination, including
incomplete visualization of the colon,
missed detection of lesions, lower procedural safety, prolonged procedure
time, and reduced interval time for
follow-up with signicant economic impact.2 Up to 20% to 30% of incomplete
colonoscopies are due to inadequate
bowel cleansing, often attributed to the
signicant discomfort associated with
the various preparation regimens.35

METHODS
Study Design
This is a single center, randomized,
observer-blind, parallel group study
conducted in Italy. The study design
was dened according to the international recognized guidelines for clinical
studies (www.clinicaltrials.gov, Identier NCT01711437) and was approved
by the local ethics committee. Written
assent from young patients and informed consent from the legal guardian and patients aged .14 years were
obtained.
Participants
Eligibleparticipantswereall childrenaged
2 to 18 years undergoing elective colonoscopyin our institution. Exclusion criteria
were (1) requirement for urgent colonoscopy, (2) bowel obstruction, (3) known or
suspected hypersensitivity to the active or
other ingredients, (4) clinically signicant
electrolyte imbalance, (5) previous intestinal resection, and (6) known metabolic, renal, or cardiac disease.

The ideal preparation should be of low

volume, palatable, and successful in
complete colon cleansing. Additionally, it
should not be associated with adverse
events including no signicant uid or
electrolyte abnormalities or effects on
histology ndings. Despite the availability
of various bowel preparations, the ideal
preparation regimen for pediatric colonoscopy remains elusive, and only few
well-controlled studies in pediatric population have been published.6,7 Available
preparations continue to represent
a challenge for children and their families because of poor taste, large volume,
and dietary restrictions with subsequent
poor compliance and need to place nasogastric tube for the administration of
intestinal lavage solution.6

Group A patients received a polyethylene

glycol 4000 (PEG) solution with simethicon
(PEG-ELS; Selg Esse, Promefarm, Italy)
starting at 4 PM the day before colonoscopy at a dose of 100 mL/Kg (maximum
4 L). The patients were instructed to drink
all the solution in 4 to 6 hours.

The primary aim of this investigatorblinded, randomized, controlled trial was

to compare the efcacy of four methods of
bowel cleansing before colonoscopy in
children. Secondary aims were to compare safety, tolerability and acceptance of
these four bowel cleansing solutions.

Group B patients received a combination of

PEG 4000 with citrates and bisacodyl (PEGCS+Bisacodyl). PEG-CS is a new sulfate-free
iso-osmotic formulation of PEG 4000 with
citrates and simethicone (Lovol-esse;
Promefarm, Milan, Italy) available as
powder to be dissolved in 2 L of water.

250

The study took place in the Pediatric

Gastroenterology Unit of the University
of Rome, Sapienza in Rome, Italy, from
January 2011 to February 2013. This unit
is an academic tertiary referral center
for pediatric IBD and for gastrointestinal endoscopy.
Interventions

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Subjects allocated to this study group

were instructed to take 1 to 4 (based
on the weight and on the constipation
questionnaire) bisacodyl 5-mg tablets
(Lovoldyl; Promefarm, Milan, Italy) at 4 PM,
followed 2 to 3 hours later by 50 mL/kg
(maximum 2 L) of PEG-CS solution. Patients were instructed to drink all the
solution in 2 to 3 hours.
Stool appearance was assessed by the
children and their parents with the
Bristol stool form chart.8 Stool type 1 or
2 was considered consistent with constipation.
Because bisacodyl could not be administered in a crushed tablet form per manufacturers recommendations, we decided
to use the following dosage: 1 tablet in
children #20 kg, 2 tablets for children
between 20 and 30 kg, and 3 tablets for
children $30 kg. In children with constipation, dosages were increased as follows: 2 tablets in children #20 kg, 3 tablets
in children between 20 and 30 kg, and 3
tablets in children $30 kg, respectively.
Group C patients received a PEG 3350
hyperosmotic solution with ascorbic acid
(PEG-Asc; Moviprep, Norgine Ltd, Hareeld,
United Kingdom) starting at 4 PM the day
before the colonoscopy at a dose of 50
mL/kg (maximum 2 L) with 25 mL/kg additional clear uid (maximum 1 L) after
completing solution intake according to
the instruction of the manufacturing
company. The patients were instructed to
drink all the solution in 2 to 3 hours.
Group D patients received 2 oral doses of
sodium picosulfate plus magnesium oxide
and citric acid (NaPico+MgCit; Picoprep,
Ferring Italia, Milan, Italy), each diluted in
150 mL of water, at 4 PM and 5 hours later
in the evening before the colonoscopy (on
quarter sachet for children ,6 years,
a half sachet for children 6 to 12 years,
and 1 sachet for children .12 years). Intake of at least 40 to 50 mL/kg (maximum
2 L) of clear uids (cold tea, sports drink,
etc) was recommended after each dose.
The age-adjusted dosage was dictated by
the instructions of the manufacturing

ARTICLE

company. No solid food intake was

allowed during the 24 hours before the
examination according to the instructions
of the manufacturing company.
In all 4 groups, a nasogastric tube was
inserted if the child failed to drink the
prescribed amount of cleanout preparation within the rst hour.
The preparations were dispensed by
a nurse who carefully explained how the
products should be taken, emphasizing
the importance of complete intake of the
solution to ensure a safe and effective
procedure. Moreover, each patient was
provided with dietary instructions: low
residue diet for 3 days before colonoscopy. During and after bowel preparation,
solid food was not allowed. Clear liquid
could be taken until 2 hours before the
procedure. All patients enrolled in this
study were scheduled for colonoscopy
before 11 AM to avoid a large variability in
the interval between bowel preparation
and colonoscopy.

TABLE 1 Boston Bowel Preparation Scale

Gradea

Findings

0
1

Unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared.
Portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen
due to staining, residual stool, and/or opaque liquid.
Minor amount of residual staining, small fragments of stool, and/or opaque liquid, but mucosa of
colon segment seen well.
Entire mucosa of colon segment seen well with no residual staining, small fragments of stool, or
opaque liquid.

2
3

a Applied to each of the 3 broad regions of the colon: right colon (including the cecum and ascending colon), transverse colon
(including the hepatic and splenic exures), and left colon (including descending colon, sigmoid colon, and rectum). Total
BBPS score ranges from 0 to 9.

a satisfactory level of concordance among

the physicians involved in the assessment
of the degree of bowel cleansing.
All examinations were performed with
a pediatric colonoscope (EVIS EXERA II
video colonoscope PCF-Q180I, Olympus,
Hamburg, Germany) under general
anesthesia (in patients ,10 years of
age, undergoing both upper and lower
endoscopy or with poor clinical conditions) or with moderate intravenous
sedation (ie, midazolam 0.1 mg/kg intravenous, maximum dosage 5 mg).

Evaluation of Bowel Preparations

Safety

Efcacy

Vital signs, complete physical examination, and blood tests were performed at
the time of patient enrollment and on the
day of colonoscopy and included liver and
kidney function test, potassium, magnesium, sodium, chlorides, and calcium.
Adverse events were assessed on the day
of colonoscopy by direct questioning and
telephone interview 48 to 96 hours after
colonoscopy. All new symptoms were
considered to be treatment related and
are included in the analysis. Any symptom
that manifested after treatment (except
those expected and included in the
evaluation of gastrointestinal tolerability)
and exacerbations of preexisting symptoms were assumed to be related to the
bowel preparation regimen.

Preparation efcacy was evaluated by the

blinded endoscopist according to the
Boston Bowel Preparation Scale (BBPS)9
consisting of a 4-point scoring system
applied to each of the 3 broad regions of
the colon: right colon, transverse colon,
and left colon (see Table 1 for details). In
addition, overall cleansing of the colon
was scored by summing up the scores of
each segment. For the study, the total
score ranging from 0 to 9 was divided into
4 classes: excellent cleansing (total score
89), good cleansing (total score 67),
poor cleansing (total score 45), and inadequate cleansing (total score 03). For
the primary efcacy variable, excellent
and good cleansing were considered
successful and poor or inadequate as
failure. Before study initiation, the 3
endoscopists (GDN, SO, and SC) performed a calibration exercise on 20 colonoscopies using the scoring system
adopted in this study (BBPS) to reach

her experience by using a standardized

questionnaire. Patients were asked
about tolerability, need for nasogastric
tube placement, acceptability, and compliance. The endoscopist was not allowed to take part in the questioning or
to supervise the questionnaire before
colonoscopy.
Tolerability assessment was based on the
recording of occurrence and severity of
gastrointestinal symptoms such as nausea, bloating, abdominal, pain/cramps,
and anal discomfort. A 5-point scale (1 =
severely distressing, 2 = distressing, 3 =
bothersome, 4 = mild, and 5 = none) was
used to score the tolerability.10 The need
for nasogastric tube insertion was also
assessed.
The easiness of taking or swallowing the
solution was graded according to the
following scale: very severe distress = 4,
severe distress = 3, moderate distress =
2, mild distress = 1, no distress = 0.
Willingness to repeat the same type of
bowel preparation if necessary was
also evaluated.
Compliance was scored on a 3-point scale
according to the percentage of solution
consumed (excellent: intake of the whole
solution; good: intakeof atleast 75%ofthe
solution; poor: intake of ,75%).
Study End Points

Tolerability, Acceptability, and

Compliance
On the morning of colonoscopy, immediately before the procedure, a nurse
questioned each patient about his or

PEDIATRICS Volume 134, Number 2, August 2014

The primary efcacy end point was the

overall colon cleansing dened as the
rate of successful cleansing (excellent and good scores in the BBPS, ie,
$6 points).
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Secondary end points included (1) the

rate of adverse events, (2) the rate of
specic symptoms associated to colonic
lavage solutions, (3) the rate of children
who declared that the intake of the solution was easy, (4) the rate of children
who declared that they would be willing to
repeat the same preparation regimen if
needed, and (5) the rate of children taking
an amount of solution $75%.
Randomization and Blinding
A randomized computer-generated list in
blocksof6waspreparedbyabiostatistician,
and eligible children were allocated to receive1ofthe4bowelpreparations,stratied
by 3 age groups: 2 to 7 years, 8 to 13 years,
and 14 to 18 years. Opaque, sealed, and
signed envelopes were prepared and
numbered to ensure sequential allocation.
Treatment was assigned by a clinic nurse
using the next numbered envelope, opened
onlyafterwrittenconsentwasobtained.The
cleanout regimen was dispensed directly to
the family.
The study was observer blind: the endoscopists were not allowed to perform any
activities associated with study preparation before and after colonoscopy and
had to avoid any discussion with the
patients and the staff, which could disclose the type of bowel preparation.
Statistical Analysis
The samples size was calculated with the
assumption of noninferiority between
high-volume and low-volume regimen. Efcacy rate of high-volume regimens was
assumed to be 80%.11 In addition, a difference of $20% of efcacy (ie, rate of
successful bowel cleansing) between the
high-volume and each of the low-volume
regimens was assumed to be clinically
relevant. To maintain the hypothesis, 5%
type I error (a), and 80% power (= 1 b),
the required sample size was estimated
to be 70 patients per each arm.
The statistical analysis was performed by
using absolute and relative frequency
tables and contingency tables. The uni-

252

variateanalysiswasconductedbyusingx2
test for categorical variables and Students test for continuous ones. Differences in prepost laboratory variables for
each group were assessed using the Wilcoxon signed-ranks test. Both intention-totreat and per protocol analysis were
provided. The noninferiority study was
limited to the primary end point, whereas
for tolerability, safety, and acceptance,
superiority of the new treatment over the
reference standard was analyzed. Because of the lack of data on the possible
improvement in tolerability and acceptance in both adult and pediatric populations, it was necessary to base our
sample size evaluation only in the primary
end point.
The statistical signicance was set at
P , .05. The analysis was conducted by
using SPSS, version 19.0.

RESULTS
Figure 1 shows the patients study ow. Of
the 299 randomized patients 11 were excluded from the per protocol analysis
(colonoscopy not performed in 8, randomized despite not meeting eligibility
criteria 1, insufcient compliance 2). The 8
patients did not perform colonoscopy for
reasons related to the hospital organization of the clinical activity and not related
to the doctor choice or to patient refusal
of the bowel solution. Two patients were
excluded from the analysis because they
added to the prescribed preparation
a PEG-based laxative in the week before
colonoscopy as commonly used in our
institution before the study.
The baseline and clinical characteristics of patients were similar for the 2
groups and are reported in Table 2.
Efcacy of Bowel Cleansing
No difference was found between the 4
groups in any of the parameters used to
evaluate the efcacy of bowel cleansing
(Table 3).
A successful cleansing level (excellent
and good scores in the BBPS, ie $6

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points) was observed in 91.7% (95%

condence interval [CI]: 83.596.5) of
PEG-ELS, in 87.5% of PEG-CS+Bisacodyl
(95% CI: 78.393.7), in 83.3% (95% CI:
73.490.6) of PEG-Asc, and in 90.3%
(95% CI: 81.795.6) of NaPico+MgCit
patients in the per protocol analysis
(P = .910).
The results were similar at intention-totreat analysis (88% vs 85.1% vs 78.9% vs
87.8%; P = .366). Details on the degrees
of level of preparation according to
BBPS scale are provided in Table 3.
Bowel cleansing was also evaluated by
colonic segment. As showed in Table 3,
no statistical signicant difference in
the efcacy of the 4 bowel-cleansing
solutions was found in the different
colonic segments.
Low-volume solutions(PEG-CS+Bisacodyl,
PEG-Asc) and NaPico+MgCit were noninferior to standard high-volume solution
(PEG-ELS) in the bowel-cleansing efcacy
of thedifferent colonic segment and of the
whole colon.
Cecal intubation rate and the time required to reach the cecum were similar
in the study groups (Table 3).
Safety and Tolerability
There was no difference in the incidence
of dehydration between the 4 study
arms, as judged by vital signs and
clinical need for intravenous uids.
Only 1 clinical adverse event occurred in
a 10-year-old girl of the PEG-ELS group
who required intravenous uid for 6
hours because of lethargy and dehydration (dryness of the oral mucosa
and orthostatic hypotension) with serum electrolyte and glucose serum
levels within the normal range.
No statistically signicant difference between the pre- and posttreatment laboratory values of kidney, liver function, and
serum electrolytes was found (Table 4).
Table 4 presents the data on patient
tolerance for the bowel preparations.
The rate of patients with none of the

ARTICLE

FIGURE 1

Study owchart.

specic symptoms associated with bowel

lavage solutions was signicantly higher in
the NaPico+MgCit group (80.6%; 95%
CI: 70.288.5) compared with PEGELS (45.8%; 95% CI: 34.657.4), PEG-

CS+Bisacodyl (51.4%; 95% CI: 39.9

62.8), and PEG-Asc (50%; 95% CI: 38.6
61.4; P , .001).
Nausea,bloating,andabdominalpainwere
the most commonly reported symptoms

TABLE 2 Demographic Characteristics of the Study Groups at Per Protocol Analysis

Variable
Sex
Male
Female
Age (y) mean (SD)
27 y, n (%)
813 y, n (%)
1418 y, n (%)
Race, n (%)
White
Black
Asian
BMI (SD), kg/m2
Indication for colonoscopy, n (%)
Suspected IBD
Bloody stools
Known IBD evaluation
Abdominal pain
Other
Constipation before bowel cleanout, n (%)
Diagnosis at colonoscopy, n (%)
Normal
Colitis (IBD)
Polyp
Other

PEG-ELS
(n = 72)

PEG-CS+Bisacodyl
(n = 72)

PEG-Asc
(n = 72)

NaPico+MgCit
(n = 72)

42 (58.3)
30 (41.7)
12.9 (4.6)
11 (15.3)
20 (27.8)
41 (56.9)

46 (63.9)
26 (36.1)
12.3 (4.2)
10 (13.9)
33 (45.8)
29 (40.3)

43 (59.7)
29 (40.3)
13 (4.5)
11 (15.3)
20 (27.8)
39 (56.9)

36 (50)
36 (50)
12.2 (4.7)
13 (18.1)
25 (34.7)
34 (47.2)

70 (97.2)
1 (1.4)
1(1.4)
20.2 (4.1)

70 (97.2)
1 (1.4)
1(1.4)
20.3 (4.1)

70 (97.2)
2 (2.8)
0 (0)
20.6 (4.4)

70 (97.2)
1 (1.4)
1(1.4)
20 (3.7)

7 (9.7)
13 (18.1)
46 (63.9)
3 (4.2)
3 (4.2)
5 (6.9)

8 (11.1)
19 (26.4)
35 (48.6)
4 (5.6)
6 (8.3)
4 (5.6)

8 (11.1)
21 (29.2)
38 (52.8)
2 (2.8)
3 (4.2)
7 (9.7)

5 (6.9)
17 (23.6)
40 (55.6)
5 (6.9)
5 (6.9)
6 (8.3)

45 (62.5)
23 (31.9)
1 (1.4)
3 (4.2)

35 (48.6)
24 (33.3)
10 (13.9)
3 (4.2)

42 (58.3)
24 (33.3)
2 (2.8)
4 (5.6)

36 (50)
24 (33.3)
5 (6.9)
7 (9.7)

and were signicantly lower in the NaPico

+MgCit group compared with PEG-ELS, PEGCS+Bysacodyl, and PEG-Asc (P , .001; Table 5).
Anal irritation was signicantly higher in
the PEG-ELS group (8.3%; 95% CI: 3.416.5)
compared with the PEG-CS+Bisacodyl
(1.4%; 95% CI: 0.016.7), PEG-Asc (1.4%;
95% CI: 0.016.7), and NaPico+MgCit (0%;
P , .001).
The percentage of children needing
nasogastric tube placement for the
infusion of the bowel-cleansing solution
was signicantly lower in the NaPico
+MgCit group (1.4%) compared with
PEG-ELS (20.8%), PEG-CS+Bysacodyl
(2.8%), and PEG-Asc (5.6%; P , .001).
Acceptability and Compliance

IBD, inammatory bowel disease.

PEDIATRICS Volume 134, Number 2, August 2014

The rate of children who stated that the

intake of the solution was easy was significantly higher in the NaPico+MgCit (91.7%;
95% CI: 83.596.6) compared with PEG-ELS
(34.7%; 95% CI: 24.446.2), PEG-CS
+Bisacodyl (81.9%; 95% CI: 30.355.2), and
PEG-Asc (61.1%; 95% CI: 49.571.8; P , .001).
The rate of children who declared that
they would be willing to repeat the same

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TABLE 3 Efcacy Outcomes Analysis at Per Protocol and Intention-to-Treat Analysis

Variable

PEG-ELS

PEG-CS+Bisacodyl

PEG-Asc

NaPico+MgCit

n = 72

n = 72

n = 72

Per protocol population

n = 72
Qualitative preparation rating, n (%)
Excellent
30 (41.7)
Good
36 (50)
Poor
6 (8.3)
Inadequate
0 (0)
Successful bowel cleansing, n (%)
66 (91.7)
BBPS score per segment, mean 6 SD
Right colon
2.13 (0.58)
Transverse colon
2.4 (0.52)
Left colon
2.38 (0.57)
Time to cecum (min), mean 6 SD
10.7 (4.3)
Caecal intubation rate (%)
72 (100)
Intention-to-treat population
N = 75
Successful bowel cleansing, n (%)
63 (88)

P
NSa

31 (43.1)
32 (44.4)
8 (11.1)
1 (1.4)
63 (87.5)

29 (40.3)
31 (43.1)
10 (13.9)
2 (2.8)
60 (83.3)

31 (43.1)
34 (47.2)
6 (8.3)
1 (1.4)
65 (90.3)

2.19 (0.66)
2.4 (0.57)
2.29 (0.61)
10.1 (3.5)
72 (100)
N = 74
61 (85.1)

2.03 (0.67)
2.32 (0.65)
2.22 (0.68)
10.4 (3.6)
72 (100)
N = 76
56 (78.9)

2.11 (0.62)
2.39 (0.59)
2.43 (0.50)
10.1 (3.8)
71 (98.6)
N = 74
63 (87.8)

NSb
NSc

NSd
NSe
NSf

NS, nonsignicant.
a P = .910, x 2 test.
b P = .423, x 2 test.
c PEG-ELS versus PEG-CS: right, P = .5; transverse: P = .9; left, P = .4. PEG-ELS versus PEG-Asc: right, P = .3; transverse: P = .4; left,
P = .1. PEG-ELS versus NaPico+MgCit: right, P = .9; transverse: P = .9; left, P = .5. Students t test in all cases.
d PEG-ELS versus PEG-CS (P = .4); PEG-ELS versus PEG-Asc (P = .6); PEG-ELS versus NaPico+MgCit (P = .4).
e P = .39, x 2 test.
f P = .4, x 2 test.

preparation regimen if needed was

signicantly higher in the NaPico+MgCit
(94.4%; 95% CI: 87.198.2) compared
with PEG-ELS (34.7%; 95% CI: 24.446.2),
PEG-CS+Bisacodyl (79.2%; 95% CI: 68.7
87.4), and PEG-Asc (66.7%; 95% CI: 55.2
76.8; P , .001).

DISCUSSION
Since the withdrawal of oral sodium
phosphate from the US market, PEG-ELS
is among the most commonly used
agents for colonoscopy preparation in
children, particularly in Europe. However, children do not tolerate well the
large volume and salty taste of these
solutions, and thus in-patient administration through nasogastric tube is
often required.7 In pediatric clinical
trials, PEG-ELS has been more effective
than active laxatives, including bisacodyl,
senna, and magnesium citrate, 5 also
showing a cleansing effectiveness

The rate of children taking an amount of

solution $75% was signicantly
higher in the NaPico+MgCit (95.8%;
95% CI: 89.098.9) compared with PEGELS (63.9%; 95% CI: 52.374.3), PEG-CS
+Bisacodyl (88.9%; 95% CI: 80.094.7),
and PEG-Asc (80.6%; 95% CI: 70.288.5;
P , .001).

similar to that of NaPico+MgCit but

with more adverse events.11
In contrast to adults, in whom lowvolume PEG solutions represent an
important alternative to standard volume formulations,12,13 there are no
pediatric data on the use of low-volume
PEG solutions.7
Our results showed, for the rst time in
children, that the tested low-volume PEG
regimens (PEG-CS+bisacodyl, PEG-Asc)
and NaPico+MgCit were noninferior
to standard high volume solution (PEGELS) in bowel-cleansing efcacy. The
high efcacy rate could be due to several factors. First, nurses expended
much time to explain, especially among
outpatients, how to take the bowel
preparations and how important it is to
take them as directed for a good colonoscopy outcome. Second, all colonoscopies were performed close to the end
of the bowel preparation (before 11 AM).
This is a factor that is well known to
positively inuence efcacy rate.14
Our data also conrmed both adult and
pediatric data on the safety of NaPico
+MgCit compared with PEG-ELS11,1517
and, for the rst time in a pediatric
population, with 2 low-volume PEG solutions (PEG-CS+bisacodyl and PEGAsc). Indeed, in our series there was
no statistically signicant difference in
the incidence of dehydration or in preand posttreatment laboratory values of
kidney and liver function and serum

TABLE 4 Mean Changes in Laboratory Values

Laboratory Variable

PEG-ELS, Mean
(SD)

Pa

PEG-CS+Bisacodyl,
Mean (SD)

Pa

PEG-Asc, Mean
(SD)

Pa

NaPico+MgCit,
Mean (SD)

Pa

Sodium (mmol/L)
Potassium (mmol/L)
Chloride (mmol/L)
Magnesium (mmol/L)
Calcium (mmol/L)
Phosphorus (mmol/L)
Creatinine (mg/dL)
AST (U/L)
ALT (U/L)
g-GT (U/L)

20.03 (5.10)
20.06 (0.60)
0.86 (5.71)
0.00 (0.13)
0.02 (0.27)
0.09 (0.38)
0.00 (0.36)
20.78 (15.01)
20.64 (12.84)
0.80 (7.88)

.969
.440
.202
.517
.650
.077
.862
.970
.575
.368

4.13 (19.98)
20.05 (0.58)
0.45 (5.47)
0.01 (0.13)
0.03 (0.30)
0.08 (0.39)
0.02 (0.32)
0.06 (14.54)
20.31 (12.40)
0.87 (9.67)

.584
.529
.472
.517
.471
.094
.591
.484
.795
.531

4.14 (19.97)
20.04 (0.56)
0.46 (5.50)
0.00 (0.14)
0.02 (0.28)
0.07 (0.40)
0.00 (0.34)
21.25 (16.78)
20.07 (12.50)
1.29 (10.14)

.583
.530
.471
.520
.467
.172
.985
.807
.904
.239

4.97 (23.25)
20.16 (0.54)
0.46 (5.50)
0.00 (0.13)
20.04 (0.27)
0.12 (0.37)
0.05 (0.36)
0.54 (12.70)
22.79 (10.48)
21.04 (9.47)

.742
.120
.068
.549
.103
.078
.244
.560
.058
.669

ALT, alanine transaminase; AST, aspartate transaminase; GT, glutamyl transpeptidase.

a Test of signicant change from screening to examination visit.

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ARTICLE

TABLE 5 Secondary End Points at Per Protocol Analysis

Variable
Tolerability
Absence of any of the following
symptoms, n (%)
Nausea
Bloating
Abdominal pain
Anal discomfort
Need for nasogastric tube
Acceptability
Ease of taking: no distress, n (%)
Willingness to repeat, n (%)
Compliance
Amount of solution intake $75%, n (%)
a

PEG-ELS PEG-CS+Bisacodyl PEG-Asc NaPico+MgCit

Pa

33 (45.8)

37 (51.4)

36 (50)

58 (80.6)

,.001

38 (52.8)
33 (45.8)
22 (30.6)
6 (8.3)
15 (20.8)

28 (38.9)
16 (22.2)
6 (8.3)
1 (1.4)
2 (2.8)

29 (40.3)
23 (31.9)
12 (16.7)
1 (1.4)
4 (5.6)

10 (13.9)
5 (6.9)
2 (2.8)
0 (0)
1 (1.4)

,.001
,.001
,.001
.010
,.001

25 (34.7)
25 (34.7)

59 (81.9)
57 (79.2)

44 (61.1)
48 (66.7)

66 (91.7)
68 (94.4)

,.001
,.001

46 (63.9)

64 (88.9)

58 (80.6)

69 (95.8)

,.001

x 2 test.

electrolytes in the 4 study groups.

There was only 1 clinical adverse event
in a 10-year-old girl from the PEG-ELS
group who required intravenous uid.
The clinical relevance of our study is
also related with the different tolerability and acceptability prole of the
four bowel-cleansing solutions. Indeed,
our data showed that NaPico+MgCit
appeared to be noninferior to the other
solutions but better tolerated and
accepted than both the standard highvolume preparation and the 2 lowvolume PEG solutions. In our opinion,
the higher tolerability and acceptability
of NaPico+MgCit accounts, at least
partially, for the noninferior efcacy of
this regimen compared with the standard 4-L PEG preparation. In contrast,
the 4-L PEG presented with an opposite
ratio between efcacy and compliance.

Meta-analyses in adult patients have

shownthattheuseofasplit-doseofPEGfor
bowel preparation signicantly improved
the number of satisfactory bowel preparations,increasedpatientcompliance, and
decreased nausea compared with the fulldose PEG.18 We did not use this approach
because in our unit, colonoscopy was
performed early in the morning, which
made it impossible to use this bowel
preparation method. We acknowledge
that this could also be a promising approach in children, and future studies are
warranted to test this hypothesis.
The main limitations of the present analysis are the single-center design; however,
the assessment of the efcacy was performed by 3 endoscopists blinded to the
method of the preparation, which makes
our results less prone to performance
bias. Second, the majority of patients had

suspected or known inammatory bowel

disease as an indication for the colonoscopy; this is mainly related to the setting
of the study and could potentially limit the
generalizability of the results. Third, the
bowel cleansing was performed in both
outpatient and inpatient settings; however,
most of the procedures were performed
on outpatients (95%), ensuring the
generalizability of the study results.
Fourth, because of the lack of comparative studies, we adopted a 3-day period of
low-residue diet before colonoscopy,
irrespectively of the regimen adopted. We
cannot exclude that a shorter period
would have similarly decreased the mean
level of bowel cleansing in all the groups.

CONCLUSIONS
In conclusion, our study shows for the
rst timein childrenthatlow-volume PEG
preparations (PEG-CS+Bisacodyl and
PEG-Asc) and NaPico+MgCit are noninferior toPEG-ELSforbowelpreparation
before colonoscopy in children. NaPico
+MgCit also appear to be better tolerated, representing a promising regimen
for bowel preparation in children.

ACKNOWLEDGMENTS
We thank Alessandra Persi and Debora
Panattoni for undertaking the important role of dispensing the products
and explaining how they should be
taken.

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BIRDING IN THE ELECTRONIC AGE: I have an aunt who is an avid birder. She can
identify an innumerable number of birds both by sight and the calls they make.
She occasionally competes in birding competitions where she tries to identify as
many birds as possible in a limited amount of time. When she does compete, she
only brings her binoculars and eld notes. Evidently, that is an old school approach. As reported in The New York Times (City Room: May 10, 2014), the world of
competitive birding is struggling with how to incorporate the use of technology.
Younger birders may compete with expensive cameras, smartphones laden with
digital eld guides, applications that play recordings of bird songs, GPS, and even
maps suggesting the best places to nd specic birds. At the heart of the issue is
whether the honor system inherent in birding is simply outdated. Birding competitions do not require proof of a sighting, relying solely on the honesty of the
contestants. Questionable sightings, called stringing, may result from inexperienced birders eager to identify birds or, more deviously, cheating. While it
is unclear that more birders are cheating in competitions, one reason to require
photographic proof of a sighting, particularly of a rare bird, is to combat
stringing. On a happier note, one reason to embrace technology is that it allows
more and younger enthusiasts to engage in the sport. Even those that eschew the
use of technology agree that anything that increases the popularity of the sport
and helps protect bird habitats is welcome, but that some balance must be
struck. After all, it is likely that sometime in the near future binoculars used for
birding will come equipped with programs that identify the birds, removing all
skill involved. As for me, I prefer walking with my aunt without any special
equipment. I take her word that the song we heard was indeed that of a specic
bird and simply enjoy our time together.
Noted by WVR, MD

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Bowel Preparations for Colonoscopy: An RCT

Giovanni Di Nardo, Marina Aloi, Salvatore Cucchiara, Cristiano Spada, Cesare
Hassan, Fortunata Civitelli, Federica Nuti, Chiara Ziparo, Andrea Pession, Mario
Lima, Giuseppe La Torre and Salvatore Oliva
Pediatrics 2014;134;249; originally published online July 7, 2014;
DOI: 10.1542/peds.2014-0131
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2014 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Bowel Preparations for Colonoscopy: An RCT

Giovanni Di Nardo, Marina Aloi, Salvatore Cucchiara, Cristiano Spada, Cesare
Hassan, Fortunata Civitelli, Federica Nuti, Chiara Ziparo, Andrea Pession, Mario
Lima, Giuseppe La Torre and Salvatore Oliva
Pediatrics 2014;134;249; originally published online July 7, 2014;
DOI: 10.1542/peds.2014-0131

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/134/2/249.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2014 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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