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Journal Reading

Oral Dimenhydrinate Versus Placebo in Children


With Gastroenteritis: A Randomized Controlled
Trial
Serge Gouin, MDCM, FRCPC,
Thuy-Tien Vo, MD, FRCPC,
Michel Roy, MD, FRCPC,
Denis Lebel, BPharm, MSc, and
Jocelyn Gravel, MD, FRCPC, MSc, (Epid)

Pembimbing : dr. Primo Parmato, Sp.A


Oleh : Dita Annisa Purwanty
Latar Belakang
Gastroenteritis akut adalah salah satu masalah pada anak yang paling
sering terjadi di seluruh dunia, dan muntah merupakan gejala umumnya.
Dimenhydrinate adalah antihistamin turunan etanolamin yang membatasi
stimulasi pusat muntah oleh sistem vestibular, yang kaya akan reseptor
histamin.
Hipotesis : anak-anak yang diobati dengan dimenhydrinate oral selama
episode akut gastroenteritis akan mengalami muntah yang lebih sedikit
dari pada anak-anak yang menerima plasebo.
Tujuan : untuk mengevaluasi efikasi dan keamanan dimenhydrinate oral
dalam pengobatan muntah pada gastroenteritis akut anak.
Metode
Randomized, double-blind, placebo-controlled.

Uji Kuesioner mengenai


kelayakan Informed
karakteristik demografi,
consent
dan kriteria riwayat medis, dan
tertulis
eksklusi gejala penyakit

Kriteria inklusi : Kriteria eksklusi :


Dehidrasi untuk Pernah mengalami kondisi kronis; keganasan; diabetes
diagnosis mellitus; jantung, endokrin, imunologi, atau gangguan
gastroenteritis. neurologis
Berumur 1-12 tahun Ada riwayat pembedahan perut atau kondisi ginekologi,
Muntah >5 kali dalam infeksi saluran kemih, migrain, atau meningitis
12 jam sebelumnya Penggunaan obat selain asetaminofen atau ibuprofen
Harus dievaluasi oleh dalam 48 jam sebelumnya
dokter anak saat mereka Riwayat alergi atau reaksi yang merugikan dimenhydrinate
berada di UGD. Dehidrasi berat yang memerlukan terapi cairan IV
Hematemesis atau hematochezia.
Hasil
Karakteristik Dasar
Characteristics Dimenhydrinate (n = Placebo (n =
74) 70)
Age, mean SD, y 4.2 2.9 3.6 2.5
Weight, mean SD, kg 18.7 9.3 16.9 9.2
Male, n (%) 42 (57) 37 (52)
Fever (history or present), n 20 (27) 19 (27)
(%)
Trial of rehydration at home, n 56 (76) 55 (79)
(%)
Overall dehydration status, n
(%)
Mild 38 (51) 36 (51)
Moderate 33 (45) 29 (41)
Severe 0 (0) 1 (2)
Duration of symptoms, mean 20.0 22.0 30.1 50.9
SD, h
No. of vomiting episodes before 11.3 6.0 12.8 7.3
randomization, mean SD
No. of diarrhea episodes before 2.2 4.6 3.0 5.1
Hasil
Outcomes Dimenhydrinate Placebo (n Difference P
(n = 74) = 70) (95% CI)
More than 1 23 (31) 20 (29) 0.02 (0.12 to .45
vomiting 0.17)
episode in the
following 24 h,
n (%)
No. of 1.0 1.3 1.6 2.7 0.61 (1.28 to .08
vomiting 0.08)
episodes in
the following
24 h, mean
SD
No. of 1.1 1.7 1.7 4.8 0.59 (1.76 to .32
diarrhea 0.58)
episodes in
the following
24 h, mean
SD
Intravenous 7 (9) 9 (13) 0.03 (0.14 to .35
insertion, n 0.07)
(%)
Nausea in the 21 (28) 26 (37) 0.10 (0.25 to .16
following 24 h, n 0.06)
(%)
Abdominal pain 19 (26) 23 (33) 0.07 (0.21 to .20
in the following 0.08)
24 h, n (%)
Total no. of 1.4 2.2 2.7 5.0 1.27 (2.56 to .05
vomiting 0.01)
episodes in 7 d,
mean SD
Total no. of 2.6 4.7 4.3 9.3 1.66 (4.11 to .18
diarrhea 0.78)
episodes in 7 d,
mean SD
Adverse effects 36 (49) 38 (54) 0.06 (0.21 to .24
in the following 0.10)
24 h, n (%)
Revisit, n (%) 11 (15) 18 (26) 0.11 (0.25 to .08
0.03)
Later 1 (1) 1 (1) 0 (0.06 to 0.06) .74
hospitalization, n
(%)
Duration of 1.0 1.4 1.6 2.4 0.52 (1.17 to .12
Efek Samping

Adverse Effects Dimenhydrinate (n = Placebo (n = 68)


69)
No adverse effects 32 (46) 31 (46)
Drowsiness 29 (42) 25 (37)
Headache 3 (4) 1 (2)
Rash 4 (6) 0 (0)
Hyperactivity 3 (4) 5 (7)
Mouth dryness 3 (4) 3 (2)
Gastrointestinal 3 (4) 3 (3)
discomfort
Mouth ulcers 1 (2) 1 (2)
Pruritus 0 (0) 1 (2)
Bronchospasm 0 (0) 1 (2)
Weakness 1 (2) 0 (0)
Nonspecific pain 0 (0) 1 (2)
Pembahasan
Dimenhydrinate oral tidak mengurangi frekuensi muntah pada anak dengan
gastroenteritis akut dibandingkan dengan plasebo.

Sesuai dengan penelitian sebelumnya yang dilakukan oleh Uhlig et al yang


mengevaluasi efikasi dan keamanan dimenhydrinate jika diberikan rektal.

Ondansetron menunjukkan hasil yang menjanjikan dalam mengurangi frekuensi


muntah di gastroenteritis akut.
Kelemahan penelitian :

Adanya bias dari dokter jaga UGD

Tidak ada data mengenai populasi yang tidak dijadikan sampel dalam
penelitian sehingga tidak semua anak suspect gastroenteritis bisa diteliti.

Tidak melakukan tes tinja rutin untuk mengidentifikasi agen infeksi serta tes
laboratorium.

Tidak ada skala dehidrasi klinis sistematis diterapkan untuk mengevaluasi


tingkat pasien dehidrasi.
Kesimpulan
Dimenhydrinate oral tidak secara signifikan mengurangi kejadian muntah
pada anak-anak yang mengalami gastroenteritis akut dibandingkan dengan
plasebo. Tidak ada efek samping yang signifikan yang dihadapi dengan
penggunaan dimenhydrinate dalam populasi penelitian.
VIA
1a. R- Was the assignment of patients to
treatments randomised?
What is best? Where do I find the
information?
Centralised computer The Methods should tell
randomisation is ideal and you how patients were
often used in multi- allocated to groups and
centred trials. Smaller whether or not
trials may use an randomisation was
independent person (e.g, concealed.
the hospital pharmacy) to
police the
randomization.
This paper: Yes No Unclear
Comment:
1b. R- Were the groups similar at
the start of the trial?
What is best? Where do I find the
information?
If the randomisation The Results should
process worked (that is, have a table of
achieved comparable "Baseline
groups) the groups Characteristics"
should be similar. The comparing the
more similar the groups randomized groups
the better it is. on a number of
There should be some variables that could
indication of whether affect the outcome
differences between (ie. age, risk factors
groups are statistically etc). If not, there
significant (ie. p values). may be a description
of group similarity in
the first paragraphs
of the Results
section.
This paper: Yes No Unclear
Comment:
2a. A Aside from the allocated
treatment, were groups treated equally?
What is best? Where do I find the
information?
Apart from the Look in the Methods
intervention the patients section for the follow-up
in the different groups schedule, and permitted
should be treated the additional treatments, etc
same, eg., additional and in Results for actual
treatments or tests. use.
2b. A Were all patients who entered
the trial accounted for? and were
they analysed in the groups to which
they were randomised?
What is best? Where do I find the
information?
Losses to follow-up should The Results section
be minimal preferably should say how many
less than 20%. However, patients were
if few patients have the randomised (eg.,
outcome of interest, then Baseline
even small losses to Characteristics table)
follow-up can bias the and how many
results. Patients should patients were
also be analysed in the actually included in
groups to which they the analysis. You will
were randomised need to read the
intention-to-treat results section to
analysis. clarify the number
and reason for losses
to follow-up.
This paper: Yes No Unclear
Comment:
3. M - Were measures objective or were
the patients and clinicians kept blind to
which treatment was being received?
What is best? Where do I find the
information?
It is ideal if the study is First, look in the Methods
double-blinded that is, section to see if there is
both patients and some mention of masking
investigators are unaware of treatments, eg.,
of treatment allocation. If placebos with the same
the outcome is objective appearance or sham
(eg., death) then blinding therapy. Second, the
is less critical. If the Methods section should
outcome is subjective describe how the outcome
(eg., symptoms or was assessed and
function) then blinding of whether the assessor/s
the outcome assessor is were aware of the
critical. patients' treatment.
This paper: Yes No Unclear
Comment:
1. How large was the treatment effect?
Most often results are presented as dichotomous outcomes (yes or not outcomes that happen or
don't happen) and can include such outcomes as cancer recurrence, myocardial infarction and
death. Consider a study in which 15% (0.15) of the control group died and 10% (0.10) of the
treatment group died after 2 years of treatment. The results can be expressed in many ways as
shown below.

What is the measure? What does it mean?


Relative Risk (RR) = risk of the outcome in The relative risk tells us how many times more likely
the treatment group / risk of the outcome it is that an event will occur in the treatment group
in the control group. relative to the control group. An RR of 1 means that
there is no difference between the two groups thus,
the treatment had no effect. An RR < 1 means that
the treatment decreases the risk of the outcome. An
RR > 1 means that the treatment increased the risk
of the outcome.
In our example, the RR = 0.10/0.15 = 0.67 Since the RR < 1, the treatment decreases the risk of
death.
Absolute Risk Reduction (ARR) = risk of The absolute risk reduction tells us the absolute
the outcome in the control group - risk of difference in the rates of events between the two
the outcome in the treatment group. This groups and gives an indication of the baseline risk
is also known as the absolute risk and treatment effect. An ARR of 0 means that there is
difference. no difference between the two groups thus, the
treatment had no effect.
In our example, the ARR = 0.15 - 0.10 = The absolute benefit of treatment is a 5% reduction
0.05 or 5% in the death rate.
Relative Risk Reduction (RRR) = absolute The relative risk reduction is the complement of the
risk reduction / risk of the outcome in the RR and is probably the most commonly reported
control group. An alternative way to measure of treatment effects. It tells us the reduction
calculate the RRR is to subtract the RR in the rate of the outcome in the treatment group
from 1 (eg. RRR = 1 - RR) relative to that in the control group.
In our example, the RRR = 0.05/0.15 = The treatment reduced the risk of death by 33%
0.33 or 33% relative to that occurring in the control group.
Or RRR = 1 - 0.67 = 0.33 or
33%
Number Needed to Treat (NNT) = inverse The number needed to treat represents the number
of the ARR and is calculated as 1 / ARR. of patients we need to treat with the experimental
therapy in order to prevent 1 bad outcome and
incorporates the duration of treatment. Clinical
significance can be determined to some extent by
looking at the NNTs, but also by weighing the NNTs
against any harms or adverse effects (NNHs) of
therapy.
In our example, the NNT = 1/ 0.05 = 20 We would need to treat 20 people for 2 years in order
to prevent 1 death.
1. How precise was the estimate of
the treatment effect?
The true risk of the outcome in the population
is not known and the best we can do is
estimate the true risk based on the sample of
patients in the trial. This estimate is called the
point estimate. We can gauge how close this
estimate is to the true value by looking at the
confidence intervals (CI) for each estimate. If
the confidence interval is fairly narrow then we
can be confident that our point estimate is a
precise reflection of the population value. The
confidence interval also provides us with
information about the statistical significance of
the result. If the value corresponding to no
effect falls outside the 95% confidence interval
then the result is statistically significant at the
0.05 level. If the confidence interval includes
the value corresponding to no effect then the
results are not statistically significant.
Will the results help me in caring for my patient? (ExternalValidity/Applicability)

The questions that you should ask


before you decide to apply the results 1) Pada penelitian ini, tidak dibedakan dalam
of the study to your patient are: pemberian perlakuan
Is my patient so different to those 2) Penelitian ini tidak dapat di aplikasikan dalam
in the study that the results cannot praktik sehari-hari
apply? 3) Penelitian ini tidak memiliki manfaat yang
Is the treatment feasible in my lebih besar dari pada efek samping yang
setting? didapatkan dari penelitian ini
Will the potential benefits of
treatment outweigh the potential
harms of treatment for my patient?
Terima Kasih