Clinical Trial Oral Ondansetron for Reducing Vomiting Secondary

7/29/2019 Clinical Trial Oral Ondansetron for Reducing Vomiting Secondary

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Clinical trial: oral ondansetron for reducing vomiting secondary

to acute gastroenteritis in children a double-blind randomized

studyH . L . Y I L M A Z * , R . D . Y I L D I Z D A S & Y . S ER T D EM I R

*Department of Pediatric Emergency

Medicine, Medical School of Cukurova

University, Adana, Turkey;

Department of Pediatric Intensive

Care Medicine, Medical School of

Cukurova University, Adana, Turkey;

Department of Biostatistics, Medical

School of Cukurova University,

Adana, Turkey

Correspondence to:

Dr H. Levent Yilmaz, Yenibaraj M.

68001 S. Gulek Plaza A Blok 69

01150 Seyhan, Adana, Turkey.

E-mail: [email protected]

Publication data

Submitted 17 July 2009

First decision 31 July 2009

Resubmitted 12 September 2009

Accepted 13 September 2009

Epub Accepted Article 16 September2009

SUMMARY

Background

Vomiting as a consequence of gastroenteritis frequently occurs in chil-

dren. It is still debatable whether vomiting should be treated with antie-

metic drugs.

AimTo investigate potential beneficial effects of ondansetron in treating

vomiting during acute gastroenteritis.

Methods

A randomized, double blind, placebo-controlled trial was performed in

our emergency departments. Children, aged 5 months to 8 years, were

randomized to receive either ondansetron 0.2 mgkg or placebo at 8h

intervals. The primary outcome measure was the frequency of emesis

during an 8-h-period after enrolment.

Results

A hundred and nine patients were enrolled; 54 received placebo and 55

received ondansetron. As compared with the children who received pla-

cebo, children who received ondansetron were less likely to vomit both

during the first 8-h follow-up in the emergency department [relative

risk (RR): 0.33, 95% CI: 0.190.56, NNT: 2, 95% CI: 1.63.5], and during

the next 24-h follow-up (RR: 0.15, 95% CI: 0.070.33, NNT: 2, 95% CI:

1.32.1).

Conclusion

Ondansetron may be an effective and efficient treatment that reduces

the incidence of vomiting from gastroenteritis during both the first 8 h

and the next 24 h, and is probably a useful adjunct to oral rehydration.

Aliment Pharmacol Ther 31, 8291

Alimentary Pharmacology& Therapeutics

82 2010 Blackwell Publishing Ltd

doi:10.1111/j.1365-2036.2009.04145.x


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INTRODUCTION

Acute gastroenteritis is a common cause of mortality

and morbidity in children and is an important health

problem worldwide.14 Current recommendations for

the treatment of acute gastroenteritis focus primarily on

the correction of dehydration and electrolyte abnormal-

ities.1, 5 Oral rehydration is recommended for the

treatment of mild-to-moderate dehydration caused by

acute gastroenteritis1, 6 and it has been shown to be safe

and cost-effective.3 However, it remains widely unde-

rused.79 Indeed, paediatric emergency physicians are

more likely to choose intravenous over oral rehydration

when the child vomits repeatedly.8, 9 According to

estimations, oral rehydration is used in under 30% of

the cases of diarrhoea in the US8, 9 and some physicians

prescribe antiemetics such as promethazine, prochlor-

perazine, trimethobenzamide and metoclopramide for

the treatment of vomiting in children with acutegastroenteritis.10, 11 However, these drugs are not

recommended because of their side effects such as

somnolence, nervousness, irritability, dystonic reactions

and other extrapyramidal symptoms.1, 6, 11, 12 On the

other hand, new antiemetics such as ondansetron and

granisetron, which have far fewer side effects, are being

used successfully in children receiving chemotherapy

and post-operative patients.13 There have been a limited

number of studies evaluating the role of ondansetron in

the treatment of acute gastroenteritis complicated by

vomiting.2, 3, 5, 7, 14, 15 Enough data have not been

collected yet to make a final judgment on the possibil-

ity of using ondansetron to support oral rehydration

treatment (ORT) in acute gastroenteritis.4, 16 Therefore,

we conducted a study to investigate potential beneficial

effects of oral ondansetron vs. placebo in treating

vomiting during acute gastroenteritis in children.

METHODS

A randomized, double blind, placebo-controlled trial

was performed in the emergency departments of one

university hospital and one government hospitalbetween August 2003 and September 2004. The study

protocol was approved by our institutional review

board and informed consent was granted by all

patients or their guardians.

All patients with symptoms consistent with acute

gastroenteritis were examined by a paediatrician (HLY),

and the patients who had nonbillious, nonbloody vomit

at least 4 times in the last 6 h, who could not tolerate

oral feeding, who had at least four episodes of diar-

rhoea in the previous 24 h, and who had mild-to-mod-

erate dehydration were included in the study. Aetiology

of acute gastroenteritis (viral, bacterial or amebic) was

not taken into account in the patients included in the

study. As an 8-h hospital observation had been

planned, only the patients presenting between 7 AM and

9 AM on the weekdays were included in the study. Those

presenting on Saturdays and Sundays were excluded.

Exclusion criteria were a history of liver disease,

ondansetron allergy or presence of any disease (such as

congenital heart disease, immune deficiency, malig-

nancy, malnutrition, cystic fibrosis, sickle cell anaemia,

diabetes mellitus), prior abdominal operation, findings

indicating a disease other than gastroenteritis on physi-

cal examination (such as focal neurologic signs,

abdominal distention, peritoneal signs, abdominal ten-

derness, shock, pneumonia), severe dehydration, an-

tiemetics use within the last 72 h, administration oforal or inhaled corticosteroids within the last week and

chronic drug use (other than vitamins). According to

the study protocol, treatment, observation and dis-

charge decisions about the patients were carried out

by two paediatricians (Dr. Ilhan Kavas and Dr. Adnan

Karacabagl), not by the investigators of the study.

The computerized randomization codes of the

patients were produced in blocks of six randomiza-

tions by a statistician, who was not one of the investi-

gators of this study, from the Department of Medical

Biostatistics in our hospital and the pharmacies of the

hospitals were given these codes. Every morning at the

pharmacies of the hospitals, orally disintegrating

ondansetron tablets were dissolved in 0.9% saline

solution of 4 mL and drawn into 5 mL injectors, and

identical looking placebo liquid of 4 mL was also

drawn into 5 mL injectors by a pharmacist who was

not one of the investigators of this study. Code num-

bers were written on the injectors in accordance with

the randomization and they were placed in the refrig-

erator. We planned to administer a total of three doses

of oral ondansetron 0.2 mgkg (0.2 mLkg) at 8 h

intervals. Therefore, the study fluid of 0.2 mLkg wasadministered by a nurse orally from injectors contain-

ing ondansetron or injectors containing placebo

according to the randomization order. The subjects,

parents, study personnel and other medical staff were

blinded to which study drug was given. Thirty minutes

after the drug was administered, the standard ORT

protocol used in both hospitals and prepared upon

the basis of WHO recommendations17 was started.

C L I N I C A L T R I A L : O N D A N S E T R O N I N P A E D I A T R I C G A S T R O E N T E R I T I S - I N D U C E D VO M I T I N G 83


2010 Blackwell Publishing Ltd


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Administration of 75 mLkg ORT solution (Ge-oral,

Kansuk, Turkey), containing 3.5 g sodium chloride,

2.9 g trisodium citrate, 1.5 g potassium chloride and

20 g glucose anhydride in each package, to patients

with observed dehydration at the rate of 0.5 mLkg

every 2 min with a spoon, glass or syringe was

ordered. During and 4 h after ORT, the success of ORT

and oral fluid tolerance were evaluated. Oral fluid tol-

erance was considered good when oral fluid intake

was 50 mLkg or over in the first 4 h, it was consid-

ered insufficient when oral fluid intake was between

20 and 49 mLkg, and it was considered lacking when

oral fluid intake was 19 mLkg or less.

All patients were re-examined by the paediatrician

at the eighth hour of ORT. However, when the patients

developed additional complaints, or when they refused

ORT, they were re-evaluated by the paediatrician with-

out delays. During each examination, the patients were

evaluated for fever, weight, hydration level, number ofvomiting, number of stools, oral intake tolerance, suf-

ficiency of oral intake, if possible, IV rehydration

necessity and hospitalization necessity. Decisions

about the patients observed throughout ORT were

made as in the following (Figure 1):

(i) At the end of the initial 8 h, the patients who

could tolerate oral intake with no vomiting were dis-

charged. Before discharge, they were given the second

dose (0.2 mLkg) of ondansetron or placebo. The study

fluid was given to the caregivers in an injector. They

were instructed the method of application and the time

of administration.

(ii) When the patients vomited more than 4 times in

the first 8 h, or 2 or more times in 1 h (except for the

first hour), intravenous fluid treatment was started and

the study protocol was discontinued.

(iii) When the patients received insufficient oral flu-

ids, showed no weight gain and vomited 34 times and

the severity of dehydration was not moderatesevere at

the end of the first 8 h, they were admitted to the pae-

diatric emergency department (ED) observation unit

and the study protocol was continued.

a. When the patients admitted to the paediatric EDobservation unit vomited three or more times and

oral intake was insufficient or none, they were

admitted to the ward, intravenous fluid treatment

was started and the study protocol was discontin-

ued.

(iv) When the fluid intake was insufficient, there

was no weight gain and vomiting occurred three or

more times, and when the severity of dehydration was

moderate at the end of the first 8 h, the children were

admitted to the paediatric ED observation unit, intra-

venous fluid treatment was started and the study pro-

tocol was discontinued.

(v) When the patients refused oral fluid intake three

times consecutively, intravenous fluid treatment was

started and the study protocol was discontinued.

(vi) As a result of an evaluation carried out 8 h

later, the patients for whom intravenous fluid treat-

ment had to be started, who had completed their

hydration and who could tolerate oral intake without

vomiting were discharged.

(vii) When abnormal findings (such as distension of

the abdomen, bloodybilious vomit, acute abdominal

findings, seizures, etc.) were detected during observa-

tion, when there was no oral intake in spite of IV fluid

treatment, when dehydration was not better, the

patients were admitted to the ward. In all these

instances, the study protocol was discontinued.(viii) When the patients showed weight loss at the

end of the first 8 h, they were admitted to the ward

and the study protocol was discontinued.

The caregivers of the patients discharged at the end

of the first 8 h were told that they would be contacted

by telephone in 16 h, and asked for information about

the patients. They were informed that they would be

asked about the general condition of the patients at

home, number of stools, number of vomiting, nourish-

ment, administration time of the study medication, side

effects of the drug and whether they had to take the

children to another doctor or hospital. The telephone

calls were made by a paediatrician (RDY) blinded to the

patients. The doctor was given a list of the names and

telephone numbers of the patients to be called at the

end of each study day by the nurse observing the

patients. When discharged patients vomited three or

more times or when they did not have oral intake or

when their oral intake was insufficient, they were asked

back to the hospital for re-evaluation. When a patient

was asked back to the hospital, Dr. RDY informed a

paediatrician (Dr. Ilhan Kavas) not involved in the

study. Re-evaluations were carried out by this paedia-trician. Records of the patients were given to the study

nurse the next day, and placed in the study file.

The primary outcome measure was the frequency of

emesis during an 8-h period after enrolment. The sec-

ondary outcomes were the rates of intravenous fluid

administration or admission to hospital, toleration of

ORT, weight gain and frequency of diarrhoea. Intrave-

nous fluid administration or hospitalization (except

84 H . L . Y I L M A Z et al.




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observation in the paediatric ED observation unit) was

considered as treatment failure.

All patients were examined for possible side effects

of ondansetron (such as diarrhoea, headache, constipa-

tion, dizziness, malaise, abdominal pain, xerostomia

and weakness etc.).

Data analysis

The study sample size was determined as in the fol-

lowing. The sample size was considered as 51 persons

in each group assuming that in the 8th hour after

treatment, the rate of vomiting in the control group

125 patientsconformed

to study criteria

11 patientsrefused to enroll

the study

109 patientsasked to enroll

the study

109 patientswere

randomized

Ondansetron55

FIRST

8HOURS

THENEXT24HOURS

FINALDECISION

Placebo54

Discharged54

24-hourobservation

1

Discharged42

24-hourobservation

10

Revisit7

Discharged1

Admission2

Revisit6

Discharged3

Discharged5

Admission6

Admission1

Admission1

ONDANSETRON PLACEBO

ORTsuccessful

44

ORTunsuccessful

10

ORTsuccessful

52

ORTUnsuccessful

3

IV fluidtreatment

1

Discharged1

Discharged4

Admission2

IV fluidtreatment

1

IV fluid treatment2

IV fluidtreatment

1

Figure 1. Patient progress throughout the trial.





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was 50%, and that there would be a 30% decrease in

the rate of vomiting in the ondansetron group, and

that the study would have a statistical power of 85%

and a = 0.05.

SPSS v16 (SPSS, Inc, Chicago, IL, USA) was used for

statistical analysis. The study was a double-blind, pla-

cebo-controlled clinical trial. T-test was used to com-

pare continuous variables like age, weight and body

temperature between the groups. MannWhitney U test

was used to compare number of diarrhoea episodes

between the groups. Chi-square test was used to com-

pare categorical variables like the degree of dehydra-

tion and emesis (vomiting) at initial presentation and

8 and 24 h after medication between the placebo and

ondansetron groups.

RESULTS

Children presenting between 7 AM and 9 AM on week-days from August 2003 to September 2004 were

included in the study. One hundred and twenty-five

patients presenting during the above mentioned period

fulfilled the study criteria. Of 125 patients, 11 did not

agree to participate. The remaining 109 patients were

enrolled in the study. Ondansetron was administered

to 55 patients and placebo to 54 patients (Figure 1).

Baseline characteristics of the two groups were not

significantly different as shown in Table 1.

Vomiting in the paediatric ED and during thestudy follow-up

At 8 h (Table 2), the frequency of emesis during obser-

vation in the paediatric ED after enrollment ranged

from 0 to 5 in the placebo group and from 0 to 3 in

the ondansetron group. The mean number of episodes

of vomiting was significantly lower among the chil-

dren who received ondansetron than among those who

received placebo (0.36 vs. 1.33, P < 0.001). In the pae-

diatric ED, during the first 8 h of observation, the pro-

portion of still vomiting patients was 21.8% in the

ondansetron group, and 66.7% in the placebo group

(Figure 2, and Table 2) and the difference between the

two groups was statistically significant [Relative risk

(RR) = 0.33; 95% confidence interval (CI) = 0.19 to

0.56, P < 0.001]. In the ondansetron group, the abso-

lute risk reduction (ARR) for vomiting was 44.9% and

the number needed to treat (NNT) was 2 (95%

CI = 1.63 to 3.55). At 24 h (Table 3), the frequency of

emesis ranged from 0 to 5 in the placebo group and

from 0 to 4 in the ondansetron group. The mean num-

ber of vomiting episodes was significantly lower

among the children who received ondansetron thanamong those who received placebo (0.2 vs. 1.66,

P < 0.001). At the end of twenty-four hours, the pro-

portion of still vomiting patients was 10.9% in the

ondansetron group, and 72.2% in the placebo group

(Figure 3) and the difference between the two groups

was statistically significant (RR = 0.15; 95% CI = 0.07

to 0.33, P < 0.001). In the ondansetron group, the

absolute risk reduction (ARR) for vomiting was 61.3%

and the NNT was 2 (95% CI = 1.3 to 2.1).

Toleration of ORT, weight gain and dehydrationstatus

At 8 h (Table 2), the proportion of the subjects in the

ondansetron group able to tolerate oral hydration was

Table 1. Demographic characteristics of the study population

Characteristics Ondansetron group (n = 55) Placebo group (n = 54) P value

Gender no. (% male) 39 (55.7) 31 (44.3) 0.141

Age months s.d. (median) 20.4 21.5 (12) 20.9 22.3 (12) 0.863

Age range months 586 694

Weight kg s.d. 9.7 3.9 10.4 3.6 0.979

Dehydration status at start, no. (%)

Normal hydration 0 0 0.451

Mild dehydration 30 (54) 32 (59)

Moderate dehydration 25 22

Vomiting no. of episodes in the

previous 24 h (mean s.d.)

6,8 2.7

median (range): 6 (420)

7.3 2.1


0.108

Diarrhoea no. of episodes in the

previous 24 h (mean s.d.)

6.8 2.2


7.2 1,7


0.134





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significantly higher than that in the placebo group

(RR = 1.17; 95% CI = 0.99 to 1.38, P = 0.06). There

were no significant differences between these two

groups in their dehydration status (ARR = 13.1%,

RR = 1.32; 95% CI = 0.94 to 1.86, P = 0.11). Weight

gain in the ondansetron group was significantly higher

than in the placebo group (ARR = 27%, RR = 2.5, 95%

CI; 1.31 to 4.61, p: 0.005).

At 24 h (Table 3), the proportion of the subjects in

the ondansetron group able to tolerate oral hydration

was not significantly higher than that of the placebo

group (ARR = 5.8%, RR = 1.07; 95% CI = 0.31 to 1.26,

P = 0.41).

Treatment failure (intravenous fluid

administration andor hospital admission)

The proportion of the patients who were not dis-

charged at the end of the first 8 h was 1.8% in the

ondansetron group and 22.2% in the placebo group,

and the difference between the two groups was statis-

tically significant (RR = 0.08; 95% CI = 0.01 to 0.61,

P = 0.014). As a result, the absolute risk reduction for

Table 2. Comparison of Groups at 8 h

Outcome at first 8 h

Ondansetron

group (n = 55)

Placebo group

(n = 54)

Relative risk

(95% CI) P value

NNT

(95% CI)

Oral hydration

accepted* no. (%)

50 (90.9) 42 (77.8) 1.17 (0.991.38) 0.06 NS

Vomiting during oralhydration no. (%)

12 (21.8) 36 (66.7) 0.33 (0.190.56)


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failure to discharge patients on ondansetron at the end

of the first 8 h would be 20.4% and the NNT was 5

(95% CI = 3.1 to 11.4).

At 24 h, the rates of return visits to the emergency

department did not differ significantly between the

groups (ARR = 1.3%, RR = 0.91; 95% CI = 0.33 to

2.50, P = 0.85). At the end of the study, the proportion

of the patients hospitalized andor subjected to intra-

venous rehydration was 5.4% in the ondansetron

group and 18.6% in the placebo group (RR = 0.29;

95% CI = 0.086 to 1.01, P = 0.04) (Table 3). At the

end of the study, we found that the absolute risk

reduction and the number needed to treat were 13.2%

and 8 (95% CI = 4.0 to 91.7) respectively in terms of

ondansetron use, hospitalization andor intravenous

rehydration treatment.

Adverse events

There were no cardiovascular, respiratory and derma-

tological side effects. However, one patient receivingondansetron was re-evaluated for a distended abdo-

men and inability of oral intake and was hospitalized.

At 8 h, there was no statistically significant difference

in diarrhoea episodes between the two groups

(Table 2). However, the children who received ondan-

setron had more episodes of diarrhoea while undergo-

ing oral rehydration than those who received placebo

at 24 h (P = 0.04) (Table 3).

89

28

7

44

4

28

0

20

40

60

80

100

Percent(%)

0Vomiting episodes

24 hours after study medication

Ondansetron Placebo

P< 0.001

3+12

Figure 3. Comparison of vomiting episodes at 24 h.

Table 3. Comparison of Groups at 24 h

Outcome at sequential 24 h

Ondansetron

group (n = 55)

Placebo

group (n = 54)

Relative risk

(95% CI) P Value

NNT

(95% CI)

Oral hydration accepted* no. (%) 48 (87.3) 44 (81.5) 1.07 (0.911.26) 0.41 NS

Vomiting during oral hydration no.(%) 6 (10.9) 39 (72.2) 0.15 (0.070.33)


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DISCUSSION

Children frequently present with gastroenteritis and

vomiting to hospitals worldwide. However, there have

been relatively few studies on vomiting, which pre-

vents the successful execution of ORT, recommended

for gastroenteritis. The most important reason for this

is that treatment of vomiting in gastroenteritis, espe-

cially use of antiemetic drugs is still debatable and

that the American Academy of Pediatrics objects to

the use of antiemetics.1 This prospective, randomized,

double blind, placebo controlled study has shown that

the rate of vomiting decreased and the success rate of

oral fluid treatment increased in patients receiving oral

ondansetron. The results we obtained in this study are

discussed in detail under the sub-headings below:

Vomiting in the paediatric ED and during thestudy follow-up

There have been five studies3, 5, 7, 14, 15 on whether

patients continued to have emesis in the emergency

departments (ER) after administration of the study drug.

The data obtained from a total of 659 participants

included in these five studies were evaluated with a

meta-analysis conducted by DeCamp et al.,18 and it

turned out that the patients who received ondansetron

were two and half times more likely to stop vomiting in

the ER (RR: 0.45, 95% CI: 0.330.62). DeCamp et al.18

estimated that five children would need to be treated

with ondansetron to prevent one child from vomiting in

the ED (95% CI, 47). Consistent with the prior studies,

the present study showed that the rate of vomiting

decreased by three folds at the end of the first 8 h after

a single dose of ondansetron. Accordingly, two children

would need to receive ondansetron to prevent vomiting

in one child (95% CI, 1.63 to 3.55).

In the present study, the rate of vomiting in children

administered a total of 3 doses of ondansetron

decreased by six times between the 8th24th hours of

the study. It means that two children would need to

receive ondansetron to prevent vomiting in one child(95% CI, 1.3 to 2.1). Consistent with the results of this

study, Cubeddu et al.2 reported that the patients trea-

ted with a single dose of ondansetron (58%) were three

times more likely to stop vomiting within 24 h than

the patients receiving placebo (17%). However, no dif-

ference was found in the vomiting frequency between

the ondansetron and placebo groups at the 24th hour

in a study by Ramsook et al.,3 and at the 24th and

72nd hours in a study by Stork et al.15 However, 10

patients from the ondansetron group and 15 patients

from the placebo group could not be reached at the

24th hour in the study by Ramsook et al.3 and there

was a large amount of missing data about the sub-

jects in the study by Stork et al.,15 and exclusion of

the data about these patients from the statistical evalu-

ation may have contributed to the results conflicting

with those from the present study.

Toleration of ORT and weight gain

In the study by Roslund et al.,14 30 min after the study

medication was administered, 32.9% of the patients in

the ondansetron group could tolerate ORT (RR: 1.73;

95% CI: 1.25 to 2.38, NNT: 3). In the present study, there

was a slightly significant decrease in the proportion of

intolerance of ORT in the ondansetron group within the

first 8 h (ARR: 13.1, RR: 1.17; 95% CI: 0.99 to 1.38,P = 0.06). The conflicting results of these two studies

might have been caused by their different criteria for

tolerance of oral intake. Unlike the study by Roslund

et al.,14 we used the criteria refusing oral intake and

amount of ORT intake. These criteria were not defined

clearly in the study by Roslund et al.14 In the study by

Stork et al.,15 ORT toleration status was evaluated 2 h

and 4 h after the study medication was administered. At

2 h, the proportion of the subjects in the ondansetron

group able to tolerate oral hydration was significantly

larger than that of the placebo group and the absolute

risk reduction (ARR) was 18.8%, with a NNT of 5 (95% CI

3 to 20). At 4 h, the proportion of the patients receiving

ondansetron and able to tolerate oral hydration

remained higher than that of the placebo group; how-

ever, the difference was not significant (RR: 1.12; 95%

CI: 0.66 to 1.92). The results of their study obtained at

the 4th hour are compatible with the results of this study.

In the present study, a weight gain of 2% or more

during ORT increased by 2.5 folds in the ondansetron

group compared with the placebo group (ARR: 27%,

RR: 2.45; 95% CI 1.31 to 4.61, NNT: 4; 95% CI, 2.3

to 9.8). A comparison with previous studies was notpossible as those studies had not evaluated weight

gain.

Dehydration status

In the study by Stork et al.,15 the only study performed

so far to evaluate dehydration status, no statistically

significant difference was determined in dehydration





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status at 2 and 4 h after the administration of the

study medication between the ondansetron, dexa-

metazone and placebo groups, which is consistent with

the results of the present study.

Failure of treatment (hospital admission andor

intravenous fluid administration)

Five studies3, 5, 7, 14, 15 of ondansetron were conducted

in the ED and included hospital admission as an out-

come. The data obtained from 662 participants in

these studies were evaluated by a meta-analysis18 car-

ried out by DeCamp et al. The relative risk (RR) of

admission after receiving ondansetron compared to

placebo during the initial ED visit was 0.52 (95% CI,

0.270.95; ARR, 7.1%). The calculated NNT showed

that 14 children would need to be treated with ondan-

setron to prevent 1 child from being admitted to hos-

pital (95% CI, 944), which is consistent with thefindings obtained during 8-h and twenty-four-hour

observations in the present study.

Adverse events

During the study, abdominal distention was observed

in one patient on ondansetron and no additional side

effects were determined. Consistent with the previous

studies,2, 3, 7 the frequency of diarrhoea in children

on ondansetron was higher in the present study

(P = 0.04).

There are several potential limitations of this study.

First, we only included the children presenting from

07.00 AM to 09.00 AM on weekdays, which led to

exclusion of many cases of acute gastroenteritis. How-

ever, the doctors and nurses responsible for treatment

of gastroenteritis and education of parents about the

issue work in the government hospital where the study

was conducted between 07.00 AM and 05.00 PM. To

conduct the study protocol properly, an 8-h-observa-

tion had to be completed until 05.00 PM and therefore,

only the children presenting between 07.00 AM and

09.00 AM were included in the study. We aimed to dis-

charge all the patients before the night shift began,

when the emergency department was the most

crowded. This allowed conducting the first 8-h period

of the study by a team knowledgeable about the study

protocol. The patients who could not be discharged till

05.00 PM were those who did not respond to treatment

or those who had a poor response to treatment. As

there were only few patients in the emergency depart-

ment, this did not cause any risk during the night

shift. Second, the telephone follow-up had the risk of

providing unreliable data. Last, culture of specimens

for bacterial or viral causes is not routinely performed

in children with gastroenteritis in our hospitals. If we

had made evaluations in terms of the aetiology of

acute gastroenteritis and had assigned the patients into

the groups based on the aetiology of gastroenteritis or

if we had included only the patients with gastroenteri-

tis because of a single aetiological factor, we could

have evaluated the results of the study more easily. Inaddition, we could have avoided the possible effects of

the cause of gastroenteritis on the obtained results.

However, this is a double-blind, randomized controlled

trial, which helped to minimize this possible negative

effect on the results.

It can be concluded that administration of orally

disintegrated tablets in children with acute gastroen-

teritis who are vomiting and unable to tolerate oral

intake and have mild-to-moderate dehydration

decreases vomiting and the ratio of hospitalization. It

can be suggested that administration of ondansetron

would be beneficial in such patients, as it has no seri-

ous side effects other than increased diarrhoea fre-

quency and it decreases the need for IV fluid

treatment and the rate of hospitalization.

ACKNOWLEDGEMENTS

Declaration of personal interests: We thank _Ilhan

Kavas, MD; Adnan Karacabagli, MD, the physician and

staff at Adana State Hospital for their assistance

throughout the study. Declaration of funding interests:

None.

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