NIHR DC Discover

NIHR Signal Risks and benefits of ondansetron for children with acute gastroenteritis

Published on 7 February 2017

doi: 10.3310/signal-000374

Giving ondansetron to children with acute gastroenteritis can stop vomiting, reduce the risk of oral rehydration treatment failing, and reduce the chances of needing intravenous rehydration. But the drug can worsen diarrhoea symptoms.

This systematic review looked for evidence about ondansetron’s effectiveness in stopping vomiting and for any impact on diarrhoea or other side effects. Only five out of the 10 included trials reported on diarrhoea related outcomes and they all used different outcome measures so the results could not be combined.

This means that although diarrhoea is a recognised side-effect, it is still not known to what extent children given ondansetron may be at risk of recurring dehydration or additional visits to healthcare professionals for diarrhoea.

NICE’s 2009 guidance on managing diarrhoea and vomiting caused by gastroenteritis in children younger than five years made a research recommendation that the effectiveness and safety of ondansetron needed to be established before it could be recommended for use and this new research adds to the evidence base.

Share your views on the research.

Why was this study needed?

Gastroenteritis is very common in children. About 10% of children younger than five years see healthcare professionals with gastroenteritis each year. A UK study found that 16% of children brought to a major paediatric emergency department were because of diarrhoea-related illness.

Vomiting is a common symptom of gastroenteritis in children. It can increase dehydration levels, and can stop oral rehydration therapy from being effective. Oral rehydration therapy is the first option for treating dehydration. Controlling vomiting could reduce the need for intravenous fluid therapy and hospital admission.

Different antiemetic drugs have been tried to reduce vomiting in children with gastroenteritis, but there are safety concerns about many of these, and none has been licensed for this specific use. A Cochrane review in 2011 included seven trials involving 1,020 participants and found that one drug in particular – ondansetron – improved outcomes, but could also worsen diarrhoea. Since then several new trials testing ondansetron have been published. These researchers aimed to look at these recent trials to see if the benefits and side effects were any clearer.

What did this study do?

This systematic review and meta-analysis pooled the results of 10 randomised controlled trials, involving 1,215 children, which compared ondansetron (oral or intravenous) with placebo or no intervention. Two trials were carried out on children admitted to hospital; the rest took place in emergency departments.

This review is limited by the quality of the trials it included. The authors report an unclear or high risk of bias in some areas for all the trials, most notably for incomplete outcome data and selective reporting. Only seven of the 10 trials gave data on the review’s primary outcome of cessation of vomiting, and only five reported on diarrhoeal outcomes.

None of the trials were carried out in the UK: five took place in the US; the others were in India, Iran, Thailand, Turkey and Venezuela.

What did it find?

  • In four trials with 540 participants, those taking ondansetron were more likely to stop vomiting after the first dose (within the first hour) than those given a placebo (risk ratio [RR] 1.49, 95% confidence interval [CI] 1.17 to 1.89, number needed to treat [NNT] 4). Three trials reported no difference in vomiting by four, 24 or 48 hours.
  • In two trials with 343 participants, there was a reduction in the risk that oral rehydration therapy would fail in those who took ondansetron (RR 0.5, 95% CI 0.37 to 0.69).
  • In three trials with 484 participants, those taking ondansetron showed a reduced risk of needing intravenous rehydration (RR 0.45, 95% CI 0.31 to 0.63).
  • Five trials reported on diarrhoeal episodes, but all used different outcome measures, so the results could not be combined. Of the five, three showed significantly more episodes of diarrhoea in the ondansetron group compared with the placebo group and two showed no difference.
  • There were large differences between the trials in terms of dose, administration method, scales used to measure outcomes and assessment of dehydration levels.

What does current guidance say on this issue?

The NICE guideline on diarrhoea and vomiting caused by gastroenteritis in under 5s, published in 2009, does not recommend the use of antiemetics.

The Guideline Development Group made a research recommendation about ondansetron, based on its review of evidence up to 2008. It concluded that although giving oral ondansetron can increase the chance of successful oral rehydration, it was unclear then whether it also worsens diarrhoea. If it does, then the guideline group suggested the significance of this effect needs to be determined, in relation to the risk of dehydration recurring or re-admission to hospital. They advised that the use of ondansetron in primary care also needs to be evaluated.

What are the implications?

This study confirms the findings of earlier systematic reviews that ondansetron can reduce vomiting and the need for intravenous rehydration in children with gastroenteritis. Diarrhoea may be worsened but this risk has not been quantified.

More evidence regarding side effects would be helpful before current UK guidance is reviewed.

Citation and Funding

Tomasik E, Ziółkowska E, Kołodziej M, et al. Systematic review with meta-analysis: ondansetron for vomiting in children with acute gastroenteritis. Aliment Pharmacol Ther. 2016;44(5):438-46.

No funding source was acknowledged for this study.

Bibliography

Armon K, Stephenson T, Gabriel V, et al. Determining the common medical presenting problems to an accident and emergency department. Arch Dis Child. 2001;84(5):390–92.

Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev. 2011;(9): CD005506.

NICE. Diarrhoea and vomiting caused by gastroenteritis in under 5s: diagnosis and management. CG84. London: National Institute for Health and Care Excellence; 2009.

NICE. Management of vomiting in children and young people with gastroenteritis: ondansetron. ESUOM34. London: National Institute for Health and Care Excellence; 2014.

Van Damme P, Giaquinto C, Huet F, et al. Multicenter prospective study of the burden of rotavirus acute gastroenteritis in Europe, 2004-2005: the REVEAL study. Journal of Infectious Diseases 2007;195 Suppl 1:S4–16.

Why was this study needed?

Gastroenteritis is very common in children. About 10% of children younger than five years see healthcare professionals with gastroenteritis each year. A UK study found that 16% of children brought to a major paediatric emergency department were because of diarrhoea-related illness.

Vomiting is a common symptom of gastroenteritis in children. It can increase dehydration levels, and can stop oral rehydration therapy from being effective. Oral rehydration therapy is the first option for treating dehydration. Controlling vomiting could reduce the need for intravenous fluid therapy and hospital admission.

Different antiemetic drugs have been tried to reduce vomiting in children with gastroenteritis, but there are safety concerns about many of these, and none has been licensed for this specific use. A Cochrane review in 2011 included seven trials involving 1,020 participants and found that one drug in particular – ondansetron – improved outcomes, but could also worsen diarrhoea. Since then several new trials testing ondansetron have been published. These researchers aimed to look at these recent trials to see if the benefits and side effects were any clearer.

What did this study do?

This systematic review and meta-analysis pooled the results of 10 randomised controlled trials, involving 1,215 children, which compared ondansetron (oral or intravenous) with placebo or no intervention. Two trials were carried out on children admitted to hospital; the rest took place in emergency departments.

This review is limited by the quality of the trials it included. The authors report an unclear or high risk of bias in some areas for all the trials, most notably for incomplete outcome data and selective reporting. Only seven of the 10 trials gave data on the review’s primary outcome of cessation of vomiting, and only five reported on diarrhoeal outcomes.

None of the trials were carried out in the UK: five took place in the US; the others were in India, Iran, Thailand, Turkey and Venezuela.

What did it find?

  • In four trials with 540 participants, those taking ondansetron were more likely to stop vomiting after the first dose (within the first hour) than those given a placebo (risk ratio [RR] 1.49, 95% confidence interval [CI] 1.17 to 1.89, number needed to treat [NNT] 4). Three trials reported no difference in vomiting by four, 24 or 48 hours.
  • In two trials with 343 participants, there was a reduction in the risk that oral rehydration therapy would fail in those who took ondansetron (RR 0.5, 95% CI 0.37 to 0.69).
  • In three trials with 484 participants, those taking ondansetron showed a reduced risk of needing intravenous rehydration (RR 0.45, 95% CI 0.31 to 0.63).
  • Five trials reported on diarrhoeal episodes, but all used different outcome measures, so the results could not be combined. Of the five, three showed significantly more episodes of diarrhoea in the ondansetron group compared with the placebo group and two showed no difference.
  • There were large differences between the trials in terms of dose, administration method, scales used to measure outcomes and assessment of dehydration levels.

What does current guidance say on this issue?

The NICE guideline on diarrhoea and vomiting caused by gastroenteritis in under 5s, published in 2009, does not recommend the use of antiemetics.

The Guideline Development Group made a research recommendation about ondansetron, based on its review of evidence up to 2008. It concluded that although giving oral ondansetron can increase the chance of successful oral rehydration, it was unclear then whether it also worsens diarrhoea. If it does, then the guideline group suggested the significance of this effect needs to be determined, in relation to the risk of dehydration recurring or re-admission to hospital. They advised that the use of ondansetron in primary care also needs to be evaluated.

What are the implications?

This study confirms the findings of earlier systematic reviews that ondansetron can reduce vomiting and the need for intravenous rehydration in children with gastroenteritis. Diarrhoea may be worsened but this risk has not been quantified.

More evidence regarding side effects would be helpful before current UK guidance is reviewed.

Citation and Funding

Tomasik E, Ziółkowska E, Kołodziej M, et al. Systematic review with meta-analysis: ondansetron for vomiting in children with acute gastroenteritis. Aliment Pharmacol Ther. 2016;44(5):438-46.

No funding source was acknowledged for this study.

Bibliography

Armon K, Stephenson T, Gabriel V, et al. Determining the common medical presenting problems to an accident and emergency department. Arch Dis Child. 2001;84(5):390–92.

Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev. 2011;(9): CD005506.

NICE. Diarrhoea and vomiting caused by gastroenteritis in under 5s: diagnosis and management. CG84. London: National Institute for Health and Care Excellence; 2009.

NICE. Management of vomiting in children and young people with gastroenteritis: ondansetron. ESUOM34. London: National Institute for Health and Care Excellence; 2014.

Van Damme P, Giaquinto C, Huet F, et al. Multicenter prospective study of the burden of rotavirus acute gastroenteritis in Europe, 2004-2005: the REVEAL study. Journal of Infectious Diseases 2007;195 Suppl 1:S4–16.

Systematic review with meta-analysis: ondansetron for vomiting in children with acute gastroenteritis

Published on 15 July 2016

Tomasik, E.,Ziolkowska, E.,Kolodziej, M.,Szajewska, H.

Aliment Pharmacol Ther , 2016

BACKGROUND: Vomiting in children with acute gastroenteritis is a common symptom, and it is considered to be the main cause of failure of oral rehydration therapy. AIM: To systematically update evidence on the effects of ondansetron (5-HT3 serotonin antagonist) for vomiting in children with acute gastroenteritis. METHODS: The Cochrane Library, MEDLINE and EMBASE databases were searched up to April 2016, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. RESULTS: Ten RCTs involving 1215 participants were included. Treatment with ondansetron compared with placebo increased the chance for vomiting cessation up to 1 h after drug administration, relative risk, RR, 1.49 (95% confidence interval 1.17-1.89), but there was no difference between the groups after 4, 24 and 48 h. Treatment with ondansetron compared with placebo reduced the risk of failure of oral rehydration therapy, RR 0.5 (0.37-0.69), increased the intake of oral rehydration solution in 1 h and 4 h, mean difference: 43 mL/1 h (15.5-70.5), and 91 mL/4 h (35-147), respectively, reduced the risk of hospitalisation, RR 0.53 (0.29-0.97), and reduced the need for intravenous rehydration, RR 0.45 (0.31-0.63); however, it had no effect on the need for return visits to the emergency department, RR 1.14 (0.72-1.8). Adverse effects were similar in both groups. CONCLUSIONS: Compared with placebo, ondansetron administration for vomiting in children with acute gastroenteritis can improve the efficacy of oral rehydration therapy.

Ondansetron is a highly selective 5HT3 receptor antagonist.

It is licensed in the UK for children and young people for nausea and vomiting either induced by chemotherapy (children aged six months and over) or for post-operative nausea and vomiting (children aged at least one month). Its precise mode of action in the control of nausea and vomiting is not known but it is probably due to antagonism of 5HT3 receptors on neurons located both in the peripheral and central nervous system. Ondansetron is not marketed for the management of vomiting in children or young people with gastroenteritis, but it is used off-label particularly in emergency departments.

Expert commentary

A GP will consult 20 children under five per year with acute gastroenteritis, mostly viral, and 1 in 140 children are admitted. Vomiting can cause failures of conservative management and ondansetron relieves vomiting in the short term, allowing rehydration. It may exacerbate diarrhoea, but doesn’t seem problematic in practice. NICE guidance doesn’t comment on ondansetron, but European guidance advocates its use to prevent progression. I suspect it’s only a matter of time before its use becomes standard in the UK, but a theoretical effect on the QT interval may ensure it remains an option in emergency care rather than primary care.

Dr James Larcombe, GP, Sedgefield

Expert commentary

This represents an interesting possible intervention to support the care of children with gastroenteritis, though key is to identify the children in whom it has been shown to be effective. The question for me as an academic GP is 'is there evidence of effectiveness in a community setting' and 'would its use risk medicalising a self-limiting illness'?

In other words, while it might be effective in reducing vomiting, might it increase consultation rates for this condition?

Alastair D Hay, GP, Professor of Primary Care and NIHR Research Professor, University of Bristol

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