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EVIDENCE BASED MEDICINE


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Content

Case summary

PICO

Search strategies Comments on article

Application to the clinical practices

Discussion


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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.


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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.


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Would treating acute gastroenteritis patient

with antiemetic (Ondansetron) lead to reduce

in vomiting and reduce in hospitalisation?


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Patient : Acute gastroenteritis

Intervention : Placebo

Comparison : OndansetroneOutcome : 1. Reduce vomiting

2. Reduce hospitalisation


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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/19758398


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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.


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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


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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.


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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.


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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.


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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.


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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.


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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


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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


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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


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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


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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


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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.


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1. Baseline data

2. Primary outcome measurements

3. Secondary outcome measurements4. Adverse events


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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.


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The primary outcome measure was the frequency ofemesis during an 8-h period after enrolment.

.


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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


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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.)


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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


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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


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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


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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.


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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.


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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


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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


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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


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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.


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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.


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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.


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H. L. YILMAZ*, R. D. YILDIZDAS & Y.

SERTDEMIR, Clinical trial: oral ondansetron

for reducing vomiting secondary to acute

gastroenteritis in children, September 2009

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