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You are a paediatric specialist registrar in a busy accident and emergency (A&E) department, and the A&E senior house officer refers to you a 3-year-old girl with a clinical diagnosis of viral gastroenteritis who has failed an oral fluid challenge (OFC). She is alert but miserable with 1–2% dehydration and is keen to drink but vomits after most fluid intake. You explain to her mother that she may need admission for nasogastric or intravenous fluids, but her mother responds by asking why you don't use medication to stop the vomiting. You wonder whether ondansetron with its relatively good side-effect profile in children might avoid this child having to be admitted and given intravenous fluids.
Structured clinical question
In children presenting with vomiting secondary to gastroenteritis [patient], does oral ondansetron [intervention] reduce vomiting, the need for intravenous fluids or admission to hospital [outcome]?
Search strategy and outcome
A primary search of Medline was conducted via PubMed using the search terms: (ondansetron or antiemetics) and (vomiting or gastroenteritis). Limits were: child <18 years, human and English language. A total of 1329 articles were found, nine of which were relevant.
A secondary search via the NHS Evidence National Library of Guidelines identified the National Institute for Health and Clinical Excellence (NICE) guideline on diarrhoea and vomiting in children. The Cochrane database revealed no further studies.
Three randomised controlled trials (RCTs) were excluded1,–,3 as they used intravenous ondansetron. Two systematic reviews4 5 and a Cochrane review6 were examined but excluded as all included intravenous ondansetron.
The management of vomiting children in A&E is frequently discussed in paediatric departments. In the UK, viral gastroenteritis is extremely common and produces a large workload for staff and a stressful experience for patients and families.
Historically, normal UK practice for the management of gastroenteritis in children without clinical signs of shock has involved the use of OFC and antipyretic medication.4 7 Despite the fact that vomiting is the major reason for failure of oral rehydration therapy,5 antiemetics have largely been considered inappropriate in paediatric patients. This is mainly due to the adverse effects of older antiemetics which include extra-pyramidal reactions and sedation. In contrast, the selective 5HT3 receptor antagonist ondansetron is a well tolerated antiemetic in children with a good side-effect profile11. Increasingly, paediatricians are suggesting that if oral ondansetron can be used to stop vomiting in children, therefore avoiding the need for intravenous fluids or admission, then it can improve the treatment of gastroenteritis in children from a medical, economic and emotional standpoint.8
The included RCTs examined children 6 months to 12 years of age with vomiting secondary to simple clinically diagnosed gastroenteritis, presenting to an A&E department. Those with systemic sepsis or significant dehydration or those who had recently undergone chemotherapy were excluded. The children were treated with oral ondansetron prior to OFC, with some trials giving multiple doses. The control groups were given an OFC after administration of placebo, or OFC alone. Otherwise treatment was according to standard care for gastroenteritis.
Previous reviews have been conducted by the Cochrane Collaboration and NICE, each with similar findings with a smaller pool of evidence. The authors of the NICE 2009 guidelines felt there was sufficient consistency of results for them to carry out meta-analyses on three of the four included RCTs6 9 10 on the need for intravenous fluids (I2, a measure of the amount of variation due to heterogeneity=0%) and need for admission (I2=21.8%). Ondansetron versus placebo gave RR 0.41 (95% CI 0.28 to 0.59) with NNT (numbers needed to treat) 5 (4–8) for need for intravenous fluids and RR 0.37 (0.17 to 0.82) with NNT 17 (9–70) for need for admission.12 The Cochrane reviewers decided that meta-analysis was inappropriate given significant clinical heterogeneity and the paucity of data.13 Since these systematic reviews, the trial by Yilmaz et al14 has provided additional data in favour of the use of ondansetron. The collective evidence from these trials provides robust evidence supporting the use of oral ondansetron as an add-on to standard therapy for gastroenteritis in children in A&E departments. The benefits include reduced need for intravenous fluids and less admission to hospital, with relatively small numbers needed to treat (although the confidence interval for required admission is broad).
The increase in diarrhoea seen with all four trials is certainly noteworthy. Only Ramsook et al10 specified it as a secondary outcome rather than an adverse event, and showed a statistically significant increase in diarrhoea. The other three studies all used orally dissolving ondansetron rather than syrup which may produce less diarrhoea (see table 1). Both the Cochrane review and the NICE guidelines comment that further research is required to assess the frequency and magnitude of this increase and whether it is significant. The NICE guidelines also provide a favourable cost-effectiveness analysis for ondansetron as it can prevent downstream resource utilisation in the form of hospital admission and intravenous medication. Increase in diarrhoea was not included in this analysis as its clinical significance is uncertain.
Clinical bottom line
▶ Oral ondansetron is a well tolerated medication in children presenting with vomiting secondary to gastroenteritis. (Grade A)
▶ Oral ondansetron produces a statistically significant reduction in the need for intravenous fluids, admissions to hospital, and amount of vomiting in these children. (Grade A)
▶ It also cause an increase in diarrhoea (Grade B), but further research is required to determine if this is clinically significant.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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