Page 131 - 15Diarrhoeaandvomiting

Diarrhoea and vomiting caused by gastroenteritis in children under 5 years

significantly more diarrhoea than those receiving placebo. In the first 24 hour period, the mean
number of diarrhoeal episodes in the ondansetron group (n = 64) was 4.70 compared with 1.37
in the placebo group (n = 54) (P = 0.002) and in the second 24 hours was 2.98 episodes (n = 62)
compared with 0.96 episodes (n = 51) (P = 0.015).
The third trial from the USA 160 included children aged 1–10 years with acute gastritis or
gastroenteritis and mild to moderate dehydration who failed ORT in the emergency department
(n = 106). Exclusion criteria were receipt of anti-emetics in the 6 hours prior to enrolment,
underlying chronic illness, shock state requiring immediate IV fluids, severe (10% or more)
dehydration, and known sensitivity to 5HT antagonists. Participants were randomised to treatment
3
with oral ondansetron (dose appropriate for weight) (n = 51) or placebo (n = 55). The methods of
randomisation were adequate and the study was conducted double-blind. With estimated failure
rates of 30% in the ondansetron group and 60% in the placebo group to achieve a power of
80% with a significance level of 0.05, 48 participants were required in each group. Outcomes
were measured daily for up to 6 days or until symptoms resolved if sooner, and were cessation of
vomiting, IV fluid administration, hospitalisation and frequency of diarrhoea. [EL = 1+]
Baseline comparability of the groups was similar except that statistically significantly more
children in the ondansetron group were ‘moderately’ dehydrated. Hence more children were
mildly dehydrated in the placebo group but this was not statistically significant. Nine percent
of participants did not participate in follow-up telephone interviews and three patients in the
ondansetron group were incorrectly diagnosed. The investigators reported that 93% of patients
who had received ondansetron had fewer than three episodes of vomiting during a 6 day follow-
up, compared with 88% of patients in the placebo group. Insufficient data were available to
establish the statistical significance of this difference or of the reported mean number of vomiting
episodes between the groups. Fewer of the children receiving ondansetron required IVT (9/48)
than those treated with placebo (30/55), the difference being statistically significant (RR 0.34;
95% CI 0.18 to 0.65). There was no statistically significant difference between groups in the
numbers of children admitted to hospital. Nineth-three percent of patients who had received
placebo had fewer than three episodes of diarrhoea during a 6 day follow-up, compared with 80%
in the ondansetron group. Insufficient data were available to establish the statistical significance
of this difference or of the reported mean number of diarrhoeal episodes between the groups.

Data on cessation of vomiting was extracted from two trials 163,164 and pooled in a meta-analysis.
The results showed that more children in the ondansetron groups stopped vomiting in the first
few hours after treatment (146/181) compared with those who received placebo (116/178). This
difference was statistically significant (RR 1.32; 95% CI 1.17 to 1.49) (Figure 8.1).
All three trials 160,163,164 compared the effects of oral ondansetron with placebo on IV hydration.
These findings were pooled in a meta-analysis which showed that fewer of the children receiving
ondansetron required IVT than those treated with placebo (79/233), with the difference being
statistically significant (RR 0.41; 95% CI 0.28 to 0.59) (Figure 8.2).
The data from the trials 160,163,164 were pooled for the number of patients admitted to hospital after
the emergency department stay. The findings showed that statistically significantly fewer children
given ondansetron were admitted to hospital (9/232) compared with those given placebo (23/233)
(RR 0.37; 95% CI 0.17 to 0.82) (Figure 8.3).
The fourth US study 161 recruited children aged 6 months to 12 years presenting to an emergency
department with paediatrician-identified acute gastritis or gastroenteritis (defined as more than
three vomits over previous 24 hours) with mild or moderate dehydration who had failed ORT.
Those with current chronic medical disease (excluding asthma), with a history of abdominal
surgery, requiring chronic medications, with inhaled or other corticosteroid or anti-emetic use in
the previous fortnight or with diagnostic findings inconsistent with isolation acute viral gastritis
were excluded. The trial had three arms and participants were randomised to a 10 minute infusion
with 0.15 mg/kg IV ondansetron (n = 46), 1 mg/kg IV dexamethasone (n = 55) or a 10 ml bolus
of normal saline (placebo) (n = 44). The methods of randomisation were adequate and patients
and outcome assessors were blinded to treatment allocation. An a priori power calculation was
done to estimate the sample size required in each group. The main outcomes measured were
need for hospitalisation, tolerance of oral hydration and dehydration status at 2 and 4 hours post
treatment, and patients were followed up to 72 hours. [EL = 1−]

106