Upload
chroniclesilie
View
222
Download
0
Embed Size (px)
Citation preview
7/31/2019 Final Edit EBM
1/42
EVIDENCE BASED MEDICINE
7/31/2019 Final Edit EBM
2/42
Content
Case summary
PICO
Search strategies Comments on article
Application to the clinical practices
Discussion
7/31/2019 Final Edit EBM
3/42
A 16 month old malay boy, presented withvomit anddiarrhoea for 1 day prior to admission.
He had vomited about 5 times per day, each time was about halfcup and no blood stained. He also passing loose stool for 4times. No bloody stool.
Otherwise, he also had low grade fever, no URTI symptomsor UTI symptoms. No similar illness in his family members.
Patient was not able to tolerate orally.
7/31/2019 Final Edit EBM
4/42
On examination, patient was not active and mildly dehydrated. No
sunkened eyeballs or fontaneles. Capillary refilling time less than 2 seconds.
Vital signs :
Temperature: 37.5 degree celcius
Pulse rate : 110bpm, regular, adequate volume
Blood pressure : 100/60mmHg
Respiratory rate : 24 breaths/min
Patient was on oral rehydration therapy. Mother was told to feedpatient with oral rehydration salt everytime patient vomit or diarrhoea.
7/31/2019 Final Edit EBM
5/42
Would treating acute gastroenteritis patient
with antiemetic (Ondansetron) lead to reduce
in vomiting and reduce in hospitalisation?
7/31/2019 Final Edit EBM
6/42
Patient : Acute gastroenteritis
Intervention : Placebo
Comparison : OndansetroneOutcome : 1. Reduce vomiting
2. Reduce hospitalisation
7/31/2019 Final Edit EBM
7/42
Search engine Pub med journal
Key words Ondansetrone AND acute gastroenteritis
Clinical study category Therapy
language EnglishDate 2001-present
Search result 27
Article selected Clinical trial: oral for reducingvomiting secondaryto in children--adouble-blind randomized study.
Yilmaz HL, Yildizdas RD, Sertdemir Y.Aliment Pharmacol Ther. 2010 Jan;31(1):82-91. Epub
http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/19758398http://www.ncbi.nlm.nih.gov/pubmed/197583987/31/2019 Final Edit EBM
8/42
7/31/2019 Final Edit EBM
9/42
7/31/2019 Final Edit EBM
10/42
Vomiting as a consequence of gastroenteritis frequently occursin children.
Current recommendations for the treatment of acute
gastroenteritis focus primarily on the correction of dehydrationand electrolyte abnormalities.
Oral rehydration is recommended for the treatment of mild-to-moderate dehydration::safe and cost-effective; but vomitingmay limit its success.
Antiemetics such as promethazine, prochlorperazine,trimethobenzamide and metoclopramide not recommendedbecause of their side effects.
7/31/2019 Final Edit EBM
11/42
Ondansetron:
far fewer side effectsBeing used in children receiving chemotherapy an
post-op patients
Limited number of studies evaluating the role of
ondansetron in the treatment of AGE complicated
by vomiting
7/31/2019 Final Edit EBM
12/42
Study design
Randomized, double-blind, placebo controlled trial.
Study duration August 2003 to September 2004.
Study site Department of Pediatric Emergency Medicine and Department of Pediatric
Intensive Care Medicine Medical School of Cukurova University, Adana, Turkey
Emergency department of one university hospital and one governmenthospital.
Approved by Institutional review board of Medical School of Cukurova University, Adana,
Turkey
Ethics Informed consent was granted by all patients or their guardians.
7/31/2019 Final Edit EBM
13/42
Children aged 5 months to 8 years old. Symptoms consistent with acute gastroenteritis
examined by a paediatrician.
Patients who had nonbillious, nonbloody vomit at least
4 times in the last 6 hour. Could not tolerate oral feeding.
At least 4 episodes of diarrhoea in the previous 24hour.
Mild-to-moderate dehydration. Patients presenting between 7 AM and 9 AM on the
weekdays
Aetiology of acute gastroenteritis (viral, bacterial or amebic) was not taken into account.
7/31/2019 Final Edit EBM
14/42
History of liver disease.
Ondansetron allergy.
Presence of any disease (congenital heart disease, immunedeficiency, malignancy, malnutrition, cystic fibrosis, sickle cellanaemia, diabetes mellitus).
Previous abdominal operation. Findings indicating a disease other than gastroenteritis on physical
examination (such as focal neurologic signs, abdominal distention,peritoneal signs, abdominal tenderness, shock, pneumonia).
Severe dehydration.
Antiemetics used within the last 72 h. Administration of oral or inhaled corticosteroids within the last
week.
Chronic drug use (other than vitamins).
Those presenting on Saturdays and Sundays.
7/31/2019 Final Edit EBM
15/42
7/31/2019 Final Edit EBM
16/42
The sample size was considered as 51persons in each group assuming that in the8th hour after treatment, the rate ofvomiting in the control group was 50%, and
that there would be a 30% decrease inthe rate of vomiting in the
ondansetron group, and that the studywould have a statistical power of 85% and =
0.05.
7/31/2019 Final Edit EBM
17/42
Randomization orally disintegratingondansetron tablets were dissolved in 0.9% saline
solution of 4 mL and drawn into 5 mL injectors, and identical lookingplacebo liquid of 4 mL was alsodrawn into 5 mL injectors
Code numbers were written on the injectors in accordance with therandomization and they were placed in the refrigerator.
The computerized randomization codes of the patients were produced inblocks of six randomizationsby a statistician
the study fluid of 0.2 mL kg was administered orally from injectorscontaining ondansetron or injectors containing placebo according to
the randomization order.
7/31/2019 Final Edit EBM
18/42
Thirty minutes after the drug was administered, the standard ORTprotocol upon the basis of WHO recommendations was started.
During and 4 hour after ORT, the success of ORTand oral fluidtolerance were evaluated
All patients were re-examined by the paediatricianat the 8th hour ofORT
During each examination, the patients wereevaluated for fever, weight,hydration level, number of
vomiting, number of stools, oral intake tolerance,
sufficiencyof oral intake, if possible, IV rehydrationnecessity andhospitalization necessity.
All patients were examined for possible side effectsof ondansetron (such asdiarrhoea, headache, constipation, dizziness, malaise, abdominal pain,
xerostomiaand weakness etc.).
Good 50 mL kg or more
Insufficient 20 and 49 mL kg
Poor 19 mL kg or less
7/31/2019 Final Edit EBM
19/42
At 8 hour evaluation
could tolerate oral intake with no
vomiting
discharged with second dose of
ondansetron or placebo
vomited three or more times
when they did not have oral intake
when their oral intake was insufficient
The caregivers of the patients discharged at the end of the first 8 h were
contacted by telephone in 16 h, and asked forgeneral condition of the patients
number of stools
number of vomiting
nourishment
administration time of the study medication
side effects of the drug
whether they had to take the children to another doctor or hospital
Asked back to the hospital for re-evaluation
7/31/2019 Final Edit EBM
20/42
vomited three or more times and oral
intake was insufficient or none
Study protocol was discontinued
received insufficient oral fluids
showed no weight gain
vomited 34 times
the severity of dehydration was mild
Admit to observation unit of ED
admitted to the ward
dehydration was moderate
IV fluid treatment
dehydration was mild
Admit to observation unit of ED
refused oral fluid intake three times
consecutively
vomited more than 4 times in the first 8
h, or 2 or more times in 1 hcompleted their hydration and who could
tolerate oral intake without vomiting
discharge
7/31/2019 Final Edit EBM
21/42
abnormal findings (such as distension of
the abdomen, bloody bilious vomit, acuteabdominal findings, seizures) were detected
during observation
no oral intake in spite of IV fluid treatment
when dehydration was not better
Admit to the ward
study protocol was discontinued
weight loss at the end of thefirst 8 h
7/31/2019 Final Edit EBM
22/42
Spss 16 was used for the statistical analysis
The study was a double-blind, placebo-controlledclinical trial.
Three types of test used:T-test: compare continuous
variables (age, weight, body T)
Mann-Whitney test: compare number of diarrhea episodes
between the groups
Chi-square test: compare categorical variables (degree of
dehydration and vomiting at presentation, 8h and 24h)
A P-value
7/31/2019 Final Edit EBM
23/42
The primary outcome measure
the frequency of emesis during an 8-h period after
enrolment.
The secondary outcomes
the rates of intravenous fluid administration or
admission to hospital, toleration of ORT, weight
gain and frequency of diarrhoea.o Intravenous fluid administration or hospitalization (except
observation in the paediatric ED observation unit) was
considered as treatment failure.
7/31/2019 Final Edit EBM
24/42
7/31/2019 Final Edit EBM
25/42
1. Baseline data
2. Primary outcome measurements
3. Secondary outcome measurements4. Adverse events
7/31/2019 Final Edit EBM
26/42
Baseline Data
Baseline demographic characteristics of gender, age, agerange, and weight were similar in both group.
The initial dehydration status, vomiting episodes in the previous 24hours, and episodes of diarrhoea in the previous 24hours were also similarin both group.
7/31/2019 Final Edit EBM
27/42
The primary outcome measure was the frequency ofemesis during an 8-h period after enrolment.
.
7/31/2019 Final Edit EBM
28/42
Episodes of vomiting during treatment and during study follow up
The proportion of still vomiting patients was lower among thechildren who received ondansetron.The
mean number of episodes of vomiting was loweramong
the children who received ondansetron
7/31/2019 Final Edit EBM
29/42
The secondary outcomes measure were the
a.Toleration of ORT
b.Weight gainc.Dehydration statusd.Treatment failure (The rates of intravenous fluidadministration or admission to hospital.)
7/31/2019 Final Edit EBM
30/42
Toleration of ORT
The proportion of the subjects in the ondansetron group able to tolerate oral
hydration was significantly higher than that in the placebo group
There was not significant in the proportion of the subjects able to
tolerate oral hydration
7/31/2019 Final Edit EBM
31/42
Weight Gain and Dehydration Status
Weight gain in the ondansetron group was significantly higher
No significant differences for the dehydration status among the
ondansetron group compared with placebo group
7/31/2019 Final Edit EBM
32/42
Treatment failure ( IV fluid administration and / or Hospital admission)
The proportion of the patients who were not discharged at the end of the first 8 hours
was significantly lower among the ondansetron group
At the end of the study, the proportion of the patients hospitalized and or subjected
to intravenous rehydration was significantly lower in the ondansetron group
7/31/2019 Final Edit EBM
33/42
Adverse Event
There was no statistically significant difference in diarrhoea episodes
between the two groups.
The children who received ondansetron had more episodes of diarrhoea while
undergoing oral rehydration than those who received placebo at 24hours.
7/31/2019 Final Edit EBM
34/42
Ondansetron may be an effective and efficient
treatment that reduces the incidence ofvomiting from gastroenteritis during boththe first 8 h and the next 24 h, and is probablya useful adjunct to oral rehydration.
7/31/2019 Final Edit EBM
35/42
7/31/2019 Final Edit EBM
36/42
Present study showed that the rate of vomiting
decreased. 1
At the end of the study, the proportion of the patientshospitalized andor subjected to intravenousrehydration was significantly lower in the ondansetrongroup 1
During the study, abdominal distention was observed inone patient on ondansetron and no additional side effects
were determined. Consistent with the previous studies, 4
1DeCamp et al. 20082Cubeddu et al.,19973Ramsook C et al.,20024Freedman SB et al.,2006
7/31/2019 Final Edit EBM
37/42
Used Randomized control trial study which is
level 1 study
Inclusion and exclusion criteria were clearly
stated
Systematic bias was adequately minimized
Statistical methods was described properly
7/31/2019 Final Edit EBM
38/42
Small sample size (n = 109)
The study was done 7 years ago (since 2003)
and just published on 2009
The study does not reflect a bigger population as it
was done among small group of people at the
Department of Pediatric Emergency Medicine and
Department of Pediatric Intensive Care MedicineMedical School of Cukurova University, Adana,
Turkey
7/31/2019 Final Edit EBM
39/42
1. This study only included the children presenting from 07.00 AMto 09.00 AM on weekdays, which led to exclusion of many casesof acute gastroenteritis.
To conduct the study protocol properly, an 8-h-observation had to be completed until
05.00
2. Telephone follow-up had the risk of providing unreliable data.
3. Culture of specimens for bacterial or viral causes is not routinelyperformed in children with gastroenteritis in this study
If we had made evaluations in terms of the aetiology of acute gastroenteritis and hadassigned the patients into the groups based on the aetiology of gastroenteritis or
if we had included only the patients with gastroenteritis because of a single aetiological
factor, we could have evaluated the results of the study more easily.
7/31/2019 Final Edit EBM
40/42
We would like to implement the use ofondansetron for paediactric patient
who presented with acute gastroenteritis andhave mild to moderate dehydration.
It can improve the toleration to ORS and
reduce hospitalization.
7/31/2019 Final Edit EBM
41/42
Administration of orally disintegrated tablets in children
with acute gastroenteritis who are vomiting and unableto tolerate oral intake and have mild-to-moderatedehydration decreases vomiting and the ratio ofhospitalization.
It can be suggested that administration of ondansetronwould be beneficial in such patients, as it has no seriousside effects other than increased diarrhoea frequency andit decreases the need for IV fluid treatment and the rate
of hospitalization.
7/31/2019 Final Edit EBM
42/42
H. L. YILMAZ*, R. D. YILDIZDAS & Y.
SERTDEMIR, Clinical trial: oral ondansetron
for reducing vomiting secondary to acute
gastroenteritis in children, September 2009