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      Antiemetic treatment for acute gastroenteritis in children: an updated Cochrane systematic review with meta-analysis and mixed treatment comparison in a Bayesian framework

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      BMJ Open

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          Abstract

          Objective

          To assess the evidence for the safety and effectiveness of antiemetics on gastroenteritis-induced vomiting in children and adolescents.

          Design

          Systematic review.

          Data Sources

          The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE searched from 1980 to March 2012.

          Methods

          Methods included comprehensive searches, data synthesis, meta-analysis and mixed treatment comparisons (MTC).

          Review methods

          Reference lists were checked, and missing or inconsistent data were sought from trial investigators. Randomised controlled trials comparing antiemetics in participants younger than 18 years and who were vomiting due to acute gastroenteritis. Four meta-analyses and three MTC were carried out.

          Results

          10 trials (1479 participants) and five treatments were included: dexamethasone, dimenhydrinate, granisetron, metoclopramide and ondansetron. There was clear evidence that ondansetron (oral or intravenous) compared with placebo increased the proportion of patients with cessation of vomiting (orally administered) (RR 1.44, 95% CI 1.29 to 1.61), reduced the immediate hospital admission rate (orally administered) (RR 0.40, 95% CI 0.19 to 0.83) and the need for intravenous rehydration therapy (orally administered) (RR 0.41, 95% CI 0.29 to 0.59). No significant difference was noted in the revisit rates, but ondansetron was associated with an increase in episodes of diarrhoea. There was no evidence for the use of dexamethasone or metoclopramide and limited evidence that dimenhydrinate or granisetron increased the cessation of vomiting. The MTC analysis suggested that ondansetron was the most likely treatment to stop the child vomiting. Nine studies were carried out in secondary care and one in primary care.

          Conclusions

          This systematic review used a method novel to this clinical area and found clear evidence that ondansetron was the most likely treatment to allow oral rehydration therapy to commence. Given the significance of these results, the authors urge healthcare policy makers to consider the wider use of ondansetron in secondary care. Furthermore, randomised controlled trials are needed to investigate the effectiveness of antiemetic treatment in primary care (including ambulatory care interventions).

          Article summary

          Article focus
          • To inform debate and clinical practice on the use of antiemetics for children presenting with vomiting associated with acute gastroenteritis in primary and secondary care.

          Key messages
          • Oral or intravenous ondansetron is the most likely treatment option to stop a child from vomiting. It reduces the need for intravenous rehydration therapy and immediate hospitalisation.

          • There is no evidence for the use of cyclizine, dexamethasone, domperidone or metoclopramide; but limited evidence was found to support the use of dimenhydrinate or granisetron.

          • Ondansetron is off patent and likely to be a cost-effective treatment for acute gastroenteritis, both the National Institute for Health and Clinical Excellence and the American Academy of Pediatrics guidance should be updated to reflect the evidence available.

          Strengths and limitations of this study
          • Ten randomised controlled trials that included 1479 participants were identified.

          • This is the first study to combine direct and indirect evidence to enable a comparison of all antiemetic treatments.

          • This review was conducted with methodological rigour and provided consistent and robust evidence to support the use of ondansetron.

          Related collections

          Most cited references 25

          • Record: found
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          Oral ondansetron for gastroenteritis in a pediatric emergency department.

          Vomiting limits the success of oral rehydration in children with gastroenteritis. We conducted a double-blind trial to determine whether a single oral dose of ondansetron, an antiemetic, would improve outcomes in children with gastroenteritis. We enrolled 215 children 6 months through 10 years of age who were treated in a pediatric emergency department for gastroenteritis and dehydration. After being randomly assigned to treatment with orally disintegrating ondansetron tablets or placebo, the children received oral-rehydration therapy according to a standardized protocol. The primary outcome was the proportion who vomited while receiving oral rehydration. The secondary outcomes were the number of episodes of vomiting and the proportions who were treated with intravenous rehydration or hospitalized. As compared with children who received placebo, children who received ondansetron were less likely to vomit (14 percent vs. 35 percent; relative risk, 0.40; 95 percent confidence interval, 0.26 to 0.61), vomited less often (mean number of episodes per child, 0.18 vs. 0.65; P<0.001), had greater oral intake (239 ml vs. 196 ml, P=0.001), and were less likely to be treated by intravenous rehydration (14 percent vs. 31 percent; relative risk, 0.46; 95 percent confidence interval, 0.26 to 0.79). Although the mean length of stay in the emergency department was reduced by 12 percent in the ondansetron group, as compared with the placebo group (P=0.02), the rates of hospitalization (4 percent and 5 percent, respectively; P=1.00) and of return visits to the emergency department (19 percent and 22 percent, P=0.73) did not differ significantly between groups. In children with gastroenteritis and dehydration, a single dose of oral ondansetron reduces vomiting and facilitates oral rehydration and may thus be well suited for use in the emergency department. Copyright 2006 Massachusetts Medical Society.
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            Uncertainty method improved on best-worst case analysis in a binary meta-analysis.

            Most systematic reviewers aim to perform an intention-to-treat meta-analysis, including all randomized participants from each trial. This is not straightforward in practice: reviewers must decide how to handle missing outcome data in the contributing trials. To investigate methods of allowing for uncertainty due to missing data in a meta-analysis. The Cochrane Library was surveyed to assess current use of imputation methods. We developed a methodology for incorporating uncertainty, with weights assigned to trials based on uncertainty interval widths. The uncertainty interval for a trial incorporates both sampling error and the potential impact of missing data. We evaluated the performance of this method using simulated data. The survey showed that complete-case analysis is commonly considered alongside best-worst case analysis. Best-worst case analysis gives an interval for the treatment effect that includes all of the uncertainty due to missing data. Unless there are few missing data, this interval is very wide. Simulations show that the uncertainty method consistently has better power and narrower interval widths than best-worst case analysis. The uncertainty method performs consistently better than best-worst case imputation and should be considered along with complete-case analysis whenever missing data are a concern.
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              • Record: found
              • Abstract: found
              • Article: not found

              A population-based estimate of the burden of diarrhoeal illness in the United States: FoodNet, 1996-7.

              This study was performed to better understand and more precisely quantify the amount and burden of illness caused by acute diarrhoea in the United States today. A telephone-based population survey was conducted between 1 July, 1996, and 31 June, 1997, in sites of the Foodborne Diseases Active Surveillance Network (FoodNet). The overall prevalence of acute diarrhoea in the 4 weeks before interview was 11%, giving a rate of 1.4 episodes of diarrhoea per person per year. The rate of diarrhoeal illness defined as a diarrhoeal episode lasting longer than 1 day or which resulted in significant impairment of daily activities was 0.7 per person per year. It can be concluded that acute diarrhoea is common and represents a significant burden of illness in the United States. Our data on self-reported diarrhoea, when generalized to the entire nation, suggests 375 million episodes of acute diarrhoea each year in the United States. Many of these episodes are mild. However, our data also indicate that there are approximately 200 million episodes of diarrhoeal illness each year in the United States.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2012
                19 July 2012
                19 July 2012
                : 2
                : 4
                Affiliations
                [1 ]North Wales Centre for Primary Care Research, Bangor University, Wrexham, UK
                [2 ]Bahrain Branch (UK CC) The Cochrane Collaboration, Awali, Bahrain
                Author notes
                Correspondence to Dr Ben Carter; ben_carter99@ 123456hotmail.com

                This review is an abridged version of a Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2011, Issue 9, doi: 20.1002/14651858.CD005506 (see http://www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review.

                Article
                bmjopen-2011-000622
                10.1136/bmjopen-2011-000622
                3401831
                22815462
                fc01e453-c2d4-41b0-a21a-0c6740f0c96c
                © 2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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                Paediatrics
                Research
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