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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.
e622
UHLIG et al
ARTICLES
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
Dimenhydrinate
(N 122)
Placebo
(N 115)
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)
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
ARTICLES
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.
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.
UHLIG et al
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
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
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UHLIG et al
ARTICLES
APPENDIX 1
e629
APPENDIX 2
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UHLIG et al
ARTICLES
APPENDIX 3
e631
Dimenhydrinate
Placebo
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
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
e632
UHLIG et al
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