Dimenhydrinate in Children With Infectious

Gastroenteritis: A Prospective, RCT

WHATS KNOWN ON THIS SUBJECT: Dimenhydrinate has
traditionally been used for children with gastroenteritis and
vomiting in Canada and Germany, but there has been no study to
evaluate its efcacy.

AUTHORS: Ulrike Uhlig, MD,a,b Nicole Pfeil, MD(sci),a,c

Gotz Gelbrich, PhD,c Christian Spranger, MD,a,c Steffen
Syrbe, MD,a Boris Huegle, MD,a Barbara Teichmann, MD,d
Thomas Kapellen, MD,a,c Peggy Houben, PhD,c Wieland
Kiess, MD,a and Hans Holm Uhlig, MD, DPhila

WHAT THIS STUDY ADDS: We performed a randomized,

controlled trial to determine the efcacy of dimenhydrinate.
Dimenhydrinate signicantly reduced vomiting but did not
improve oral rehydration and did not decrease the rate of
hospitalization.

aSection of Pediatric Gastroenterology, University Hospital for

Children and Adolescents, University of Leipzig, Leipzig,
Germany; bSection of Pediatric Gastroenterology, University
Hospital for Children and Adolescents, Martin Luther University
Halle, Halle, Germany; cCoordination Centre for Clinical Studies
Leipzig, Leipzig, Germany; and dPrivate Pediatric Practice,
Leipzig, Germany

KEY WORDS
gastroenteritis, vomiting, dimenhydrinate, children, randomized,
controlled trial

abstract
OBJECTIVE: Vomiting is a common symptom in children with infectious
gastroenteritis. It contributes to uid loss and is a limiting factor for
oral rehydration therapy. Dimenhydrinate has traditionally been used
for children with gastroenteritis in countries such as Canada and Germany. We investigated the efcacy and safety of dimenhydrinate in
children with acute gastroenteritis.
METHODS: We performed a prospective, randomized, placebocontrolled, multicenter trial. We randomly assigned 243 children with
presumed gastroenteritis and vomiting to rectal dimenhydrinate or
placebo. Children with no or mild dehydration were included. All children received oral rehydration therapy. Primary outcome was dened
as weight gain within 18 to 24 hours after randomization. Secondary
outcomes were number of vomiting episodes, uid intake, parents
assessment of well-being, number of diarrheal episodes, and admission rate to hospital. We recorded potential adverse effects.
RESULTS: Change of weight did not differ between children who received dimenhydrinate or placebo. The mean number of vomiting episodes between randomization and follow-up visit was 0.64 in the dimenhydrinate group and 1.36 in the placebo group. In total, 69.6% of
the children in the dimenhydrinate group versus 47.4% in the placebo
group were free of vomiting between randomization and the follow-up
visit. Hospital admission rate, uid intake, general well-being of the
children, and potential adverse effects, including the number of diarrhea episodes, were similar in both groups.

ABBREVIATIONS
CI condence interval
NNTnumber needed to treat
Drs U. Uhlig and H. Uhlig initiated the study, developed the initial
study design, contributed to day-to-day work, were involved in
the data analysis, and wrote the rst draft of the manuscript;
Drs Gelbrich and Kapellen contributed to the study design; Dr
Gelbrich developed the statistical aspects of the study design,
performed the data analysis, and wrote parts of the manuscript;
Drs Spranger, Kapellen, Houben, and Kiess contributed to the
coordination of the study; and Drs U. Uhlig, Spranger, Syrbe,
Huegle, Kapellen, and H. Uhlig and Ms Pfeil recruited patients. All
authors discussed and contributed to the manuscript.
This trial has been registered at European Union Drug
Regulating Authorities Clinical Trials (identier 2005-003943-30;
international standard randomized, controlled trial No.
53730137).
www.pediatrics.org/cgi/doi/10.1542/peds.2008-1650
doi:10.1542/peds.2008-1650
Accepted for publication Jun 1, 2009
Address correspondence to Hans Holm Uhlig, MD, DPhil,
University Hospital for Children and Adolescents, University of
Leipzig, Section of Pediatric Gastroenterology, Liebigstrasse 20a,
D-04103 Leipzig, Germany. E-mail: holm.uhlig@medizin.unileipzig.de
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2009 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.

CONCLUSIONS: Dimenhydrinate reduces the frequency of vomiting in

children with mild dehydration; however, the overall benet is low,
because it does not improve oral rehydration and clinical outcome.
Pediatrics 2009;124:e622e632

e622

UHLIG et al

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ARTICLES

Infectious gastroenteritis is 1 of the

most frequent infectious diseases in
childhood.1 The majority of children
develop vomiting in the initial phase
of the disease. Vomiting causes discomfort and contributes to uid loss.
Vomiting is a limiting factor for oral
rehydration therapy in children with
infectious gastroenteritis. Oral rehydration is the recommended therapy
in children with mild to moderate dehydration that is caused by infectious gastroenteritis.13 Ondansetron
has been shown to reduce vomiting in children with infectious
gastroenteritis.412
Rectal dimenhydrinate has been used
for children with gastroenteritis and
vomiting in Canada and Germany,13 but
no studies of its effect have been published. Rectal administration of antiemetics in children with diarrhea may
not be efcient.14 The sedative effect of
dimenhydrinate might counteract the
antiemetic effect by reducing overall
uid intake. We performed a randomized, controlled trial to determine
whether dimenhydrinate is effective in
improving oral rehydration, reducing
vomiting, and decreasing the rate of
hospitalization.

METHODS
The Vomiting-Enteritis-Dimenhydrinate
study (VomED) was a prospective,
double-blind, placebo-controlled, multicenter phase IV trial that investigated
the efcacy of dimenhydrinate on oral
rehydration therapy during infectious
gastroenteritis and vomiting in children. Patients were recruited in 5 childrens hospitals (University Childrens
Hospital Leipzig, University Childrens
Hospital Mainz, St Georg Hospital
Leipzig, St Elisabeth and Barbara Hospital Halle/Saale, and Childrens Hospital Wurzen) and 6 pediatric practices
(Leipzig and Rotha) in Germany. Study
recruitment was performed during
2 consecutive autumn-to-spring seaPEDIATRICS Volume 124, Number 4, October 2009

sons (December 1, 2005, to May 31,

2006, and October 1, 2006, to May 31,
2007). Written informed consent was
obtained from at least 1 parent before
enrollment in the study. The study followed the principles of good clinical
practice (European good clinical practice guidelines www.emea.europa.eu/
pdfs/human/ich/013595en.pdf and as
specied by German law as of September 8, 2004).
The study was approved by the University of Leipzig Ethics Committee (19605), by local ethics committees, and by
the German Federal Institute for Drugs
and Medical Devices. Data validation
and quality control procedures included external monitoring of study
sites.
Patients
Inclusion criteria were (1) age between 6 months and 6 years, (2) suspected infectious gastroenteritis, (3)
acute (24 hours) onset of vomiting
with at least 2 episodes within the last
12 hours, (4) outpatient attendance,
and (5) body weight of 7 kg. We excluded children with moderate to severe gastroenteritis, on the basis of 1
of the following criteria: (1) acute
weight loss of 5% of body weight; (2)
bloody stools; (3) necessity of intravenous rehydration therapy; or (4) metabolic acidosis (pH 7.25) and/or electrolyte disturbances (blood tests were
conducted at the discretion of the
treating physician, only for a minority
of children). We also excluded children
with preexisting diseases for which dimenhydrinate is contraindicated (eg,
epilepsy, glaucoma, acute asthma,
porphyria, pheochromocytoma), current treatment with drugs that are
suspected to interact with dimenhydrinate, or treatment with antiemetics or
secretion inhibitor racecadotril within
this episode of gastroenteritis. Simultaneous participation in other medical
trials was not allowed. Children for

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whom intravenous rehydration therapy was indicated were hospitalized.

Randomization and Stratication
Patients were randomly assigned to
receive dimenhydrinate or placebo
suppositories (Table 1). Randomization was stratied by category of body
weight (15 and 15 kg). An independent biostatistician from Sandoz Pharmaceuticals, Germany (GmbH, Holzkirchen, Germany), generated the
randomization list according to our
study protocol. For each stratum, a
blocked random allocation sequence
was generated (block randomization
in blocks of 4). Medication kits were
consecutively numbered and assigned
to the patients according to their stratum and the order of recruitment in
the respective study site.
Study Intervention
The rst suppository (40 mg of dimenhydrinate or placebo) was given in the
outpatient department or pediatric
practice. Additional suppositories of
the same type (40 mg of dimenhydrinate or placebo) were provided, depending on body weight (15 kg: 1
suppository; 1525 kg: 2 suppositories; 25 kg: 3 suppositories). Caregivers were instructed to give additional
suppositories only in case of persistent vomiting or in case of visible excretion of the suppository immediately
after administration. Both dimenhydrinate and placebo suppositories were
manufactured and supplied by Sandoz
Pharmaceuticals, Germany (formerly
Hexal AG, Holzkirchen, Germany).
Concomitant Treatment
Each patient received 10 sachets of
powdered oral rehydration solution (1
sachet corresponds to 200 mL of reconstituted solution containing 100
mmol/L glucose, 60 mmol/L sodium,
and 20 mmol/L potassium; osmolarity
240 mosm/L [Stada Arzneimittel, Bad
Vilbel, Germany]). All parents were exe623

TABLE 1 Description of the Study Groups at the Time of Randomization

Parameter

Dimenhydrinate
(N 122)

Placebo
(N 115)

Male gender, n (%)

Age, mean SD, y
Weight, mean SD, kg
15, n (%)
15, n (%)
Vomiting episodes within 24 h before enrollment, n (%)
2
3
45
5
Episodes of diarrhea within 24 h before enrollment, n (%)
0
13
3
Unknown
Dehydration, n (%)
None
Mild
Moderate
Severe
Unknown
Co-medication, n (%)
Antipyretics
Antibiotics
Probiotics
Other

68 (55.7)
2.5 1.5
13.3 4.4
86 (70.5)
36 (29.5)

68 (59.1)
2.3 1.5
13.0 4.3
81 (70.4)
34 (29.6)

33 (27.0)
28 (23.0)
34 (27.9)
27 (22.1)

25 (21.7)
31 (27.0)
30 (26.1)
29 (25.2)

53 (43.4)
42 (34.4)
25 (20.5)
2 (1.6)

49 (42.6)
42 (36.5)
20 (17.4)
4 (3.5)

65 (53.3)
52 (42.6)
5 (4.1)
0 (0.0)
0 (0.0)

65 (56.5)
47 (40.9)
2 (1.7)
0 (0.0)
1 (0.9)

37 (30.3)
9 (7.4)
13 (10.7)
30 (24.6)

33 (28.7)
6 (5.2)
11 (9.6)
34 (29.6)

plicitly instructed on oral rehydration

therapy and early feeding and received
an information leaet.
Follow-up Visit and Telephone
Interview
A short-term follow-up visit in the
study center was scheduled 18 to 24
hours after randomization. Patients
underwent physical examination and
weight measurement, and history
was recorded by using a structured
interview.
For long-term follow-up, a research assistant called the families for a telephone interview 7 to 14 days after enrollment. Again, a history was obtained
by a structured questionnaire. Case
report forms of the randomization
visit, the follow-up-visit, and the telephone interview are provided in Appendices 1 to 3.
Outcome Measures
The primary clinical end point was the
relative weight gain from randomizae624

UHLIG et al

scale), adverse events, and use of comedication, each recorded for the interval between randomization and
follow-up visit. Long-term outcome recorded in the structured telephone interview included severe adverse
events that required hospitalization,
time until recovery, and parent satisfaction with treatment (numeric scale
from 1 [best] to 6 [worst]).
Adverse Events
Sedation; paradoxic excitement; drowsiness; skin reaction; and hospitalization
as a result of gastroenteritis, were
predened as expected adverse
events. Fever, vomiting, and diarrhea
are symptoms of gastroenteritis and
hence were not considered to be adverse events.
Data Collection and Statistical
Analysis

tion to follow-up visit after 18 to 24

hours: (weightfollow-up weightrando)/
weightrando. This means that the spectrum relative weight gain is between
1 and 1. Weight loss would lead to
negative and weight gain to positive
values. When a child was hospitalized
as a result of gastroenteritis within 24
hours after randomization, the end
point was formally set at 1 for primary analysis. This means that hospitalization was counted as the worst
possible outcome. By including cases
with hospitalization (ie, presumably
severe dehydration and dramatic
weight loss) into analysis, a potential
selection bias was prevented.

All patient data were entered in a study

database at the coordination center
for clinical studies of the University
of Leipzig. The database was not accessible to non-clinical study investigators. At no point did any of the companies involved have access to patient data, case report forms, or the
study database. After recruitment of
the last patient, after recording of all
patient data, and after response to all
queries that arose during the monitoring process, the study database was
closed. The rst analysis was performed blinded to the study medication as an intention-to-treat analysis,
knowing the allocation to 2 groups but
not the allocation to dimenhydrinate
or placebo.

Secondary early outcome measures

were the number of episodes of vomiting, the number of diarrheal episodes,
the volume of uid intake, hospitalization as a result of gastroenteritis, wellbeing of the child as assessed by the
parents on a 6-point smiley scale
(equivalent to the Wong-Baker faces

Primary analysis was conducted by the

Mann-Whitney U test. Because we expected that relative changes of weight
might be larger in small children, the
stratied version of this test was used.
Stratication was done by baseline
weight, dividing children into 4 groups
according to the quartile of weight. The

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ARTICLES

test statistic was then computed using

the ranks within the strata (instead of
global ranks); thereby, only children of
similar initial weights were compared
with each other.
For secondary analysis, t tests were
used to evaluate quantitative outcomes, and 2 statistics were used for
frequencies. Posthoc analysis was performed to describe the outcome measure as a function of the severity of
diarrhea (Appendix 5).
Sample Size
A mean difference of 1.5% of relative
change of weight was considered a
clinically relevant effect. SD was anticipated to be 3% on the basis of clinical
experience. With these assumptions,
210 patients were needed to achieve a
power of 0.95 at type I error level of
0.05. We planned to terminate recruitment when 210 patients completed the
study or 270 patients were randomly
assigned.

RESULTS
Participants
A total of 243 eligible children were
randomly assigned to 2 study groups:
124 to dimenhydrinate and 119 to placebo (Fig 1). Six patients were excluded because they did not match the
eligibility criteria. After the follow-up
visit, 208 patients were available for
analysis of primary and 199 for analysis of secondary end points. A total of
224 patients could be reached for telephone follow-up. Reasons for missing
the follow-up visit were full recovery of
the child (5 in the dimenhydrinate
group versus 2 in the placebo group),
illness of family members (2 vs 1), and
personal logistic problems (3 vs 5).
Outcome at the Follow-up Visit
The change of body weight between
randomization and follow-up visit was
similar in both groups. Mean relative
gain of body weight was 0.14% (SD:
PEDIATRICS Volume 124, Number 4, October 2009

FIGURE 1
Enrollment of patients, randomization, stratication, follow-up visit, telephone interview, withdrawal,
and completion of the study.

1.96%) in the dimenhydrinate group

and 0.06% (SD: 1.74%) in the placebo
group (P .452; Table 2), with marginal differences across weight quartile subgroups. Four children in the dimenhydrinate group and 5 in the
placebo group were hospitalized for
gastroenteritis within 18 to 24 hours.
The mean number of episodes of vomiting between randomization and
follow-up visit was 0.64 in the dimenhydrinate group and 1.36 in the placebo
group (difference: 0.72 [95% condence interval (CI): 1.16 to 0.29]).
At the follow-up visit, 69.6% in the dimenhydrinate versus 47.4% in the placebo group were free of vomiting (P
.001). Numbers needed to treat
(NNTs) were 2 (95% CI: 1 to 4) to avoid
1 episode of vomiting and 5 (95% CI: 3

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to 12) for complete cessation of vomiting. Additional use of the study

medication was reported in 30.4% of
children in the dimenhydrinate
group and in 54.6% of the placebo
group (P .001).
Mean frequencies of diarrheal episodes were 1.75 and 1.74, respectively
(P .720). The amount of uid intake
and the improvement of well-being of
the child according to parents assessment were similar in both groups.
Sedation occurred in 22 (21.6%) children who received dimenhydrinate
and in 18 (18.6%) children who received placebo. One (1%) child in each
group had rash, and drowsiness was
reported for 1 (1%) child in the dimenhydrinate group. Three severe adverse
e625

TABLE 2 Main and Secondary Outcomes and Adverse Events

Parameter

Dimenhydrinate

Placebo

Primary outcome, n
Absolute weight change, mean SD, kg
Relative weight change, mean SD, %
Hospitalizations, n (%)
Primary test: rank by baseline weight, mean, kg
7.2 to 9.6
9.6 to 12.5
12.5 to 16.0
16.0 to 30.0
Secondary outcomes, n
Frequency of vomiting, mean SD
Vomiting episodes, n (%)
0
1
2
3
Frequency of diarrhea, mean SD
Oral uid intake, mean SD, mL
Repetitive administration of suppositories, n (%)
Parents reported outcome measure: improvement
of general well-being, mean SDa
Adverse events, n (%)
Sedation
Drowsiness
Exanthema
Others
Severe adverse events, n
RSV bronchiolitis
Upper airway infection
Unspecied circulatory system disorder

106
0.02 0.23
0.14 1.96
4 (3.8)

102
0.01 0.25
0.06 1.74
5 (4.9)

25.2
27.0
25.7
27.2
102
0.64 1.27

27.7
25.9
27.3
25.7
97
1.36 1.79

71 (69.6)
16 (15.7)
7 (6.9)
8 (7.8)
1.75 1.93
701.5 361.5
31 (30.4)
1.35 1.37

46 (47.4)
19 (19.6)
8 (8.2)
24 (24.7)
1.74 1.81
679.0 282.4
53 (54.6)
1.14 1.50

.720
.627
.001
.669

22 (21.6)
1 (1.0)
1 (1.0)
0 (0.0)

18 (18.6)
0 (0.0)
1 (1.0)
1 (1.0)

.596
1.000
1.000
.980

0
0
0

1
1
1

.471
.452
.744
.863

.001
.001

Parameters refer to the period between visits 1 and 2. RSV indicates respiratory syncytial virus.
a Scale: 1 indicates very well; 6, bad.

events were reported in the placebo

group. Two children were hospitalized
for respiratory tract infections, and
the third child was hospitalized for
mild cardiovascular disorder and social problems. All children fully recovered. In no case was hospitalization attributed to the study medication (Table
2).
Outcome at Telephone Follow-up
Overall, 10 dimenhydrinate versus 13
placebo patients were hospitalized;
among those, 9 vs 11 were hospitalized
for gastroenteritis. Mean duration of
vomiting was 0.60 days in the dimenhydrinate group versus 0.94 days in the
placebo group (difference: 0.34 [95%
CI: 0.66 to 0.02]; P .036) and 1.40
vs 1.40 days among those who vomited
after the rst dose of study medication
(P .99). Children were able to return
e626

UHLIG et al

to their child care facility 2.91 vs 3.21

days (difference: 0.29 [95% CI 1.35
to 0.77]; P .588) after randomization.
Mean parental satisfaction rating was
2.39 vs 2.31 (difference: 0.08 [95% CI:
0.28 to 0.45]; P .651).
Intention-to-Treat and Subgroup
Analysis
We performed an intention-to-treat
analysis. Similar to the main analysis
in the dimenhydrinate group, we found
a reduced number of vomiting episodes (mean SD: 0.68 1.37 vs
1.41 1.81; P .001), a decreased
risk for repeated vomiting (33 [30.0%]
vs 56 [53.8%]; P .001), and a decreased risk for repeated administration of suppositories (34 [30.9%] vs 58
[55.8%]; P .001). No other signicant
differences were observed. For detailed analysis, see Appendix 4.

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Because not all children who were enrolled as a result of vomiting developed diarrhea during the observation
period, we performed a posthoc subanalysis for children with diarrhea episodes (24 hours before randomization
until follow-up visit). A total of 78% of
children who were available for the
intention-to-treat analysis developed
diarrhea. Similar to the intention-totreat analysis and the main analysis,
we found a reduced number of vomiting episodes (mean SD: 0.64 1.26
vs 1.38 1.85; P .004), a decreased
risk for repeated vomiting (24 [31.2%]
vs 38 [51.3%]; P .002), and a decreased risk for repeated administration of suppositories (23 [29.9%] vs 43
[58.1%]; P .001). No other signicant
differences were observed. In children
with more pronounced diarrhea, similar results were obtained. For detailed
analysis, see Appendix 5.

DISCUSSION
Dimenhydrinate reduced the number of
vomiting episodes in children who had
vomiting as a result of gastroenteritis
and had no or mild dehydration. The
number of children with complete cessation of vomiting was 1.5 times higher in
the dimenhydrinate group (70% dimenhydrinate versus 47% placebo; NNT 5).
Dimenhydrinate was well tolerated, and
the number of adverse effects was not
different in the 2 groups.
The primary outcome measure was
the difference of body weight between
initial presentation and follow-up visit.
We wanted to investigate whether uid
loss as a result of vomiting is reduced
and rehydration is made easier by dimenhydrinate. The degree of dehydration was measured by body weight development and by a standardized
assessment scale.2 We could not observe any effect on oral rehydration.
Antiemetic treatment in children with
gastroenteritis-associated vomiting is
a widespread phenomenon.13 Dimen-

ARTICLES

hydrinate is a classic H1-antihistaminic

drug that also shows antiallergic activity and benecial effects on motion
sickness and drowsiness. It has been
shown to reduce postoperative vomiting in children.15 In Germany and Canada, dimenhydrinate is the preferred
antiemetic treatment in children with
gastroenteritis13; however, concerns
have been raised that dimenhydrinate
might delay other diagnoses in children with vomiting,16 and dimenhydrinate intoxication has been reported.17
We did not encounter a delay of other
diagnoses as a result of medication
with dimenhydrinate. Our data suggest
that dimenhydrinate is safe in children
with mild gastroenteritis.
Dopamine receptor antagonists such
as domperidone and metoclopramide
are frequently used in Italy, Spain, and
France, whereas, in the United States,
promethazine is the antiemetic treatment of choice in children with gastroenteritis.13,18,19 None of those drugs
showed a consistent antiemetic benet in children with gastroenteritis in
randomized, controlled trials.8 The
5-HT3 receptor antagonist ondansetron plays only a marginal role in clinical practice13; however, according to a
recently published meta-analysis of 6
randomized, controlled trials, ondansetron decreased the risk for hospital
admission (NNT 14 [95% CI: 9 44]),
for intravenous rehydration (NNT 5
[95% CI: 4 8]), and for persistent emesis (NNT 5 [95% CI: 4 7]).8 In our
study, the benecial antiemetic effect
of dimenhydrinate (NNT 5 [95% CI:
312]) was comparable to that reported for ondansetron. In contrast to
studies on ondansetron, dimenhydrinate did not decrease the rate of hospitalization. In contrast to 3 of 6 studies
on ondansetron,8 the rate of diarrhea
was not increased by dimenhydrinate.
According to guidelines for treatment of
infectious gastroenteritis, we did not
perform routine stool smears to identify
PEDIATRICS Volume 124, Number 4, October 2009

the infectious agent, and laboratory

tests such as blood gas analysis were
not performed routinely. The study was
conducted during 2 winter seasons,
when the annual peak incidence of viral
gastroenteritis occurs and bacterial infections are less common.
Because we investigated children with
no or mild dehydration in our study, it is
possible that there is a spectrum effect.
Recently, Goldman et al20 validated a clinical dehydration scale for children with
gastroenteritis. A total of 57% of children
who presented in the emergency department had no dehydration, 41% of children had some dehydration, and 2% had
moderate or severe dehydration. According to Goldman et al, a mild degree
dehydration is a typical nding in North
America, because children present early
during the course of illness. Our study
included a spectrum of children that is
typical for the majority of children who
have gastroenteritis and present to pediatricians, whereas the studies on ondansetron were performed on moderately ill
patients. The authors of a recent metaanalysis consequently stated that there
is a need to investigate patients with
mild disease.8
We did not perform a cost-effectiveness
or cost benet analysis for using dimenhydrinate in children with acute gastroenteritis. In the United States, costs of
ondansetron have been estimated to be
$15 to $25 (in-house pharmacies up to
$50) per pill,8 whereas costs of dimenhydrinate are approximately 0.4 to 0.5 per
suppository of 40 mg. This price difference is most likely one of the main reasons that dimenhydrinate is frequently
prescribed to children with acute gastroenteritis in Germany. Although the
medication costs of ondansetron are
much higher, the overall health care
costs might still be reduced because of
reduced need for hospitalization. In a pilot study that compared ondansetron
with dimenhydrinate in children with
postoperative vomiting, despite higher

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medication costs of ondansetron, the

overall costs were reduced.21 Prospective, randomized, controlled trials are
needed to compare the antiemetic effects and therapeutic benets and to estimate the overall cost/benet relation of
ondansetron and dimenhydrinate in
children with gastroenteritis-associated
vomiting.

CONCLUSIONS
Dimenhydrinate signicantly reduces
vomiting in children with gastroenteritis and is well tolerated; however, the
antiemetic effect of dimenhydrinate is
mild and oral rehydration therapy and
clinical outcome are not improved. It is
not clear whether dimenhydrinate
would have more pronounced effects
in children with a higher degree of
dehydration.

ACKNOWLEDGMENTS
The investigator-initiated study was
funded by the nonprot Hexal-Initiative
on Childrens Medication after a competitive grant application procedure
and independent expert decision. The
grant was provided unconditionally.
Sandoz Pharmaceuticals GmBH Germany (formerly Hexal AG, Holzkirchen)
supplied dimenhydrinate and placebo
suppositories, and Stada Arzneimittel
AG (Bad Vilbel, Germany) supplied the
oral rehydration solution. The companies had no role in the conception, design, or conduct of the study or in the
analysis or interpretation of the data.
We thank all the participating parents,
children, and pediatricians. The following pediatricians contributed to the
study: S. Beblo, M. Behrens, M. Bernhard, A. Bigl, H. Eichner, C. Falkenberg,
L. Fischer, A. Galler, K. Frenzel, D. Hartig, S. Herbertz, C. Jorck, A. Keller, A.
Klossek, A. Korner, M. Landgraf, B.
Lesener, S. Liebermann, C. Henn, U.
Mutze, F. Schlensog, A. Siegler, V.
Schuster, P. Suchowerskyj, and F.
Wild (University Childrens Hospital
e627

Leipzig); U. Dietz (St Georg Hospital

Leipzig); T. Kofer, A. Fensterer, and K.
Steul (University Hospital Mainz); and
A. Fiegert, F. Hornemann, A. Rentzsch,
K. Mock, S. Springer, C. Kurzke, G.

Schleicher, J. Streidl, and M. Thole

(Hospital Wurzen). We are grateful to O.
Brosteanu, M. Vissiennon, N. Bauernfeind, A. Franke, K. Schosnig, and M.
Dorschmann for discussions, monitor-

ing, and data management support.

We also thank P. Schoettler and B. Muhlbauer for continuous support and S.
Koletzko and N. Blanchette for critical
comments on the manuscript.

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6. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D. A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann
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ARTICLES

APPENDIX 1

Case Report Form for Time of Randomization (English Translation)

PEDIATRICS Volume 124, Number 4, October 2009

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APPENDIX 2

Case Report Form for the Follow-Up Visit (English Translation)

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ARTICLES

APPENDIX 3

Case Report Form for the Telephone Interview (English Translation)

PEDIATRICS Volume 124, Number 4, October 2009

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APPENDIX 4 Main and Secondary Outcomes According to Intention-to-Treat Analysis

Parameter

Dimenhydrinate

Placebo

Available for primary end point, n

Hospitalized, n
Absolute weight change, mean SD
% weight change, mean SD
Available for secondary end points, n
Vomiting episodes, mean SD
Episodes of vomiting 0/1/2/3, n
Diarrheal episodes, mean SD
Oral uid intake, mean SD, mL
Repeated administration of suppositories, n (%)
Parents reported outcome measure:
improvement of well-being, mean SD

114
4
0.02 0.23
0.15 1.99
110
0.68 1.37
77/16/7/10
1.83 1.99
707 358
34 (30.9)
1.30 1.35

109
5
0.01 0.24
0.08 1.71
104
1.41 1.81
48/20/9/27
1.76 1.79
672 283
58 (55.8)
1.15 1.49

.346
.368
.001
.001
.788
.426
.001
.436

Parameters refer to the period between visits 1 and 2.

APPENDIX 5 Main and Secondary Outcomes for Various Degrees of Gastroenteritis

Parameter
Patients with at least 1 episode of diarrhea in total
Remaining in study ow, n
Available for primary end point, n
Hospitalized, n
Absolute weight change, mean SD
% weight change, mean SD
Available for secondary end points, n
Vomiting episodes, mean SD
Vomiting episodes 0/1/2/3, n
Episodes of diarrhea, mean SD
Oral uid intake, mean SD, mL
Repeated administration of suppositories, n (%)
Parents reported outcome measure:
improvement of well-being, mean SD
Patients with at least 2 episodes of diarrhea in total
Remaining in study ow, n
Available for primary end point, n
Hospitalized, n
Absolute weight change, mean SD
% weight change, mean SD
Available for secondary end points, n
Vomiting episodes, mean SD
Vomiting episodes 0/1/2/3, n
Episodes of diarrhea, mean SD
Oral uid intake, mean SD, mL
Repeated administration of suppositories, n (%)
Parents reported outcome measure:
improvement of well-being, mean SD
Patients with at least 3 episodes of diarrhea in total
Remaining in study ow, n
Available for primary end point, n
Hospitalized, n
Absolute weight change, mean SD
% weight change, mean SD
Available for secondary end points, n
Vomiting episodes, mean SD
Vomiting episodes 0/1/2/3, n
Episodes of diarrhea, mean SD
Oral uid intake, mean SD, mL
Repeated administration of suppositories, n (%)
Parents reported outcome measure:
improvement of well-being, mean SD

Dimenhydrinate

Placebo

90
79
2
0.03 0.24
0.25 2.07
77
0.64 1.26
53/13/5/6
2.32 1.90
713 356
23 (29.9)
1.17 1.39

84
76
2
0.00 0.24
0.06 1.79
74
1.38 1.85
36/14/5/19
2.26 1.76
704 299
43 (58.1)
0.97 1.50

75
68
2
0.01 0.24
0.18 2.14
66
0.74 1.33
42/13/5/6
2.64 1.87
714 370
20 (30.3)
1.14 1.46

75
67
2
0.00 0.23
0.02 1.81
65
1.52 1.90
28/14/5/18
2.48 1.76
723 304
40 (61.5)
0.98 1.58

59
53
2
0.02 0.25
0.30 2.21
51
0.84 1.46
32/9/4/6
3.04 1.89
746 399
16 (31.4)
1.18 1.49

65
59
2
0.02 0.23
0.02 1.81
57
1.39 1.76
25/13/5/14
2.68 1.76
731 292
35 (61.4)
1.05 1.48

.425
.326
.004
.002
.820
.884
.001
.402

.850
.573
.007
.004
.616
.879
.001
.564

.380
.231
.086
.043
.315
.838
.002
.659

Parameters refer to the period between visits 1 and 2.

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Dimenhydrinate in Children With Infectious Gastroenteritis: A Prospective,

RCT
Ulrike Uhlig, Nicole Pfeil, Gtz Gelbrich, Christian Spranger, Steffen Syrbe, Boris
Huegle, Barbara Teichmann, Thomas Kapellen, Peggy Houben, Wieland Kiess and
Hans Holm Uhlig
Pediatrics 2009;124;e622; originally published online September 14, 2009;
DOI: 10.1542/peds.2008-1650
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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,
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Dimenhydrinate in Children With Infectious Gastroenteritis: A Prospective,

RCT
Ulrike Uhlig, Nicole Pfeil, Gtz Gelbrich, Christian Spranger, Steffen Syrbe, Boris
Huegle, Barbara Teichmann, Thomas Kapellen, Peggy Houben, Wieland Kiess and
Hans Holm Uhlig
Pediatrics 2009;124;e622; originally published online September 14, 2009;
DOI: 10.1542/peds.2008-1650

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/124/4/e622.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 2009 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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