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Other therapies

when compared with placebo, is dominant owing to an increase in the cessation of vomiting
and net savings due to a reduction in IVT and lower rates of hospitalisation. A probabilistic
sensitivity analysis (PSA) was carried out which showed that the results were not sensitive to
parameter uncertainty within the economic model, with ondansetron dominant in 99.96% of
simulations. Although some trials reported changes in diarrhoea in response to ondansetron,
this was not included in the economic model mainly because of the uncertainty of the clinical
significance of this and whether or not increased diarrhoea would lead to increased use of NHS
resources. Limitations of the model, particularly with regard to diarrhoeal outcomes, need to be
addressed by further research in order to make firm conclusions regarding the cost-effectiveness
of ondansetron.

GDG translation from evidence to recommendation

Although many children vomit during ORT, this is usually not so severe as to prevent oral
rehydration. Occasionally, vomiting is frequent and persistent. In such cases, a decision might be
made to administer ORS solution by nasogastric tube or to change to IVT. The availability of an
effective anti-emetic could therefore be very valuable. The GDG considered that evidence from
randomised controlled trials indicated that oral ondansetron could increase the success rate with
ORT. The GDG was concerned that ondansetron might have adverse effects such as worsening
diarrhoea. There was no evidence to support other agents, including metoclopramide and
dexamethasone. The GDG concluded that administration of anti-emetics could not currently be
recommended. However, the GDG did consider that further research on the use of ondansetron
was needed, focusing particularly on the possible risk of worsened diarrhoea.

Research recommendation

In children with persistent vomiting caused by gastroenteritis, is oral ondansetron cost-effective
and safe compared with placebo therapy?

Why this is important
Several randomised controlled trials have shown that in children with persistent vomiting
during oral rehydration therapy, administration of oral ondansetron, an anti-emetic agent, can
increase the likelihood of successful oral rehydration. However, in two of these there was
evidence suggesting that diarrhoea was more pronounced in those given ondansetron than
in those in the placebo groups. In one, in children given ondansetron, the number of stools
passed during the rehydration phase was significantly greater, and in the other the number of
stools passed in the first and second 24 hour period after rehydration was significantly greater.
In those studies, diarrhoea was not a primary outcome, and it was reported as an adverse
event. The reliability of the finding was therefore somewhat uncertain. If ondansetron does
worsen diarrhoea it would be crucially important to determine the clinical significance of this
effect, for example in relation to the risk of dehydration recurring or re-admission to hospital.
If ondansetron is shown to be both effective and safe in secondary care then studies should
also be undertaken to evaluate its use in primary care.

8.2 Antidiarrhoeal agents

A range of drugs have been used as antidiarrhoeal agents in patients with gastroenteritis and
other disorders. Adsorbent agents such as clay minerals (kaolin or smectite) and charcoal have
been employed. Antisecretory drugs such as racecadotril (a peripherally acting enkephalinase
inhibitor) reduce intestinal water and electrolyte secretion. Bismuth subsalicylate (BSS) has
a number of properties that may be important in reducing diarrhoea, including inhibition of
intestinal fluid secretion, suppression of intestinal inflammation and a bactericidal action. Anti-
motility agents such as loperamide may reduce diarrhoea by lengthening intestinal transit time
and hence absorption.
Nowadays it is generally advised that these medicines should be avoided in the treatment of
children with gastroenteritis. Nevertheless, it was considered important to review the available
evidence in relation to the use of these agents.

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