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Antiemetics in Children with Acute Gastroenteritis: a Meta-Analysis Laura F

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Antiemetics in Children with Acute Gastroenteritis: a Meta-Analysis Laura F Antiemetics in Children With Acute Gastroenteritis: A Meta-analysis Laura F. Niño-Serna, MD, MSc,a,b Jorge Acosta-Reyes, MD, MSc,c Areti-Angeliki Veroniki, PhD,d,e,f Ivan D. Florez, MD, MSca,g CONTEXT: Several antiemetics have been used in children with acute gastroenteritis. However, abstract there is still controversy over their use. OBJECTIVE: To determine the effectiveness and safety of antiemetics for controlling vomiting in children with acute gastroenteritis. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Latin America and the Caribbean Literature on Health Sciences, and gray literature, until December 2018. STUDY SELECTION: We selected randomized clinical trials comparing metoclopramide, ondansetron, domperidone, dexamethasone, dimenhydrinate, and granisetron. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model. RESULTS: Twenty-four studies were included (3482 children). Ondansetron revealed the largest effect in comparison to placebo for cessation of vomiting (odds ratio = 0.28 [95% credible interval = 0.16 to 0.46]; quality of evidence: high) and for hospitalization (odds ratio = 2.93 [95% credible interval = 1.69 to 6.18]; quality of evidence: moderate). Ondansetron was the only intervention that reduced the need for intravenous rehydration and the number of vomiting episodes. When considering side effects, dimenhydrinate was the only intervention that was worse than placebo. LIMITATIONS: Most treatment comparisons had low- or very low–quality evidence, because of risk of biases and imprecise estimates. CONCLUSIONS: Ondansetron is the only intervention that revealed an effect on the cessation of vomiting, on preventing hospitalizations, and in reducing the need for intravenous rehydration. Ondansetron was also considered a safe intervention. aDepartment of Pediatrics, University of Antioquia, Medellín, Colombia; bHospital Pablo Tobón Uribe, Medellín, Colombia; cDepartment of Public Health, Universidad del Norte, Barranquilla, Colombia; dDepartment of Primary Education, School of Education, University of Ioannina, Ioannina, Greece; eLi Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, Canada; fDepartment of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College, London, United Kingdom; and gDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada Dr Niño-Serna conceptualized and designed the study, performed the data collection, evidence synthesis, and quality-of-evidence assessment, drafted the initial manuscript, and reviewed and revised the manuscript; Dr Acosta-Reyes performed the data collection, evidence synthesis, and quality-of-evidence assessment and critically reviewed the manuscript as submitted; Dr Veroniki performed the statistical analyses, drafted the initial manuscript, and critically reviewed the manuscript as submitted; Dr Florez conceptualized and designed the study, performed the evidence synthesis and quality-of-evidence assessment, drafted the initial manuscript, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. To cite: Niño-Serna LF, Acosta-Reyes J, Veroniki A, et al. Antiemetics in Children With Acute Gastroenteritis: A Meta-analysis. Pediatrics. 2020;145(4):e20193260 Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 145, number 4, April 2020:e20193260 REVIEW ARTICLE Diarrheal diseases remain the third whereas dimenhydrinate revealed Search strategies were developed in cause of death among children a positive effect on vomiting duration. liaison with an experienced librarian ,5 years old, mostly in low- and Nevertheless, the authors did not (Supplemental Information). We used middle-income countries.1,2 Although compare antiemetics among them validated filters for identifying in high-income countries the disease and included only 7 studies. Later, pediatric articles and RCTs.7,12 No is rarely fatal, it is a leading cause of Carter et al10 performed a network language or publication status limits emergency department (ED) visits meta-analysis (NMA) including all the were used. We performed gray and hospitalizations.3 The American antiemetics for which there was literature searches through trial Academy of Pediatrics defines acute evidence at that time. The authors registries (www.clinicaltrials.gov and gastroenteritis as a diarrheal disease found that ondansetron was the best World Health Organization Clinical of rapid onset, with or without intervention to reduce vomiting, the Trials Registry Platform). additional symptoms and signs, such need for intravenous rehydration, and as nausea, vomiting, fever, or hospitalizations. However, some Eligibility Criteria 4 abdominal pain. Furthermore, acute concerns were raised because We included RCTs and quasi RCTs in fi diarrhea is de ned by the World ondansetron was associated with an which authors evaluated antiemetics Health Organization as the passage of increase of diarrhea. used for controlling vomiting in 3 or more loose or liquid stools per In the last decade, many randomized children with ADG. Our interventions , day for 3 or more days but 14 clinical trials (RCTs) comparing of interest were metoclopramide, 5 fi days. Both de nitions refer to the different antiemetics to placebo or ondansetron, domperidone, same disease: acute diarrhea and against each other have been dexamethasone, dimenhydrinate, gastroenteritis (ADG), that is, an published and have not been yet alizapride, and granisetron at any infectious episode of the synthesized. Specifically, new dose and presentation in children gastrointestinal tract. evidence from trials studying with ADG and vomiting. Researchers In addition to diarrhea, ADG dexamethasone, metoclopramide, had to compare any of the commonly presents with vomiting.5 domperidone, and ondansetron have interventions against them, a placebo, Vomiting is particularly challenging been available. To date, there is no conventional treatment with ORT, or for parents and health care systematic review or NMA comparing different doses or administration professionals because it can hinder all the currently available antiemetics routes of the same intervention and oral rehydration therapy (ORT), in children with ADG. Therefore, we had to report at least 1 of the worsen dehydration, and cause aimed to assess the relative outcomes of interest. hospitalizations.6 In most cases, ORT effectiveness and safety of can help to control vomiting. antiemetics in children with ADG Outcomes However, in some cases, vomiting is through direct and indirect Our primary outcomes were cessation severe and may affect the ORT comparisons using an NMA. of vomiting and hospitalization. The success. Therefore, some antiemetics secondary outcomes included the have been used to control vomiting in METHODS need for intravenous rehydration children with ADG. Nevertheless, (measured as the number of This systematic review was some clinical practice guidelines participants who required registered in the PROSPERO (CPGs) do not recommend intravenous rehydration during the International Prospective Register of antiemetics because some of them ED stay and up to 3 days after Systematic Reviews have shown significant side effects.4,7 discharge); revisit to the ED (CRD42016035236). This article In contrast, other CPGs8 recommend (measured as the number of complies with the recommendations ondansetron and have discouraged participants that revisited the ED up of the PRISMA (Preferred Reporting the use of other antiemetics because to 72 hours after discharge); number Items for Systematic Reviews and of lack of evidence. of vomiting (measured as the mean Meta-Analyses) extension for NMA.11 number of vomiting episodes during The evidence of antiemetics for ADG the observation period); and side was first synthesized by Fedorowicz Search Process effects. et al.9 In this review, ondansetron We searched Medline (Ovid), Embase revealed a significant effect on (Ovid), Cochrane Central Register of Regarding side effects, as a post hoc cessation of vomiting and the need Controlled Trials, Cumulative Index to analysis, we analyzed side effects for intravenous rehydration. Also, Nursing and Allied Health Literature, (any side effect reported by the metoclopramide was found to be and Latin America and the Caribbean authors) and diarrhea separately. We effective in reducing vomiting Literature on Health Sciences from separated the outcomes because episodes and hospital admissions, the inception to December 31, 2018. diarrhea was reported as Downloaded from www.aappublications.org/news by guest on September 29, 2021 2 NIÑO-SERNA et al a dichotomous (presence or absence Assessment of Risk of Bias in NMA Included Studies of diarrhea in the observation) and We performed an NMA to analyze continuous variable (mean number of We assessed, independently and in all the potential comparisons among diarrheal stools), with the latter being duplicate, all included studies for interventions for each outcome. An the most commonly reported. The their risk of bias (RoB) using NMA, also known as multiple- presence of diarrhea (dichotomous) a modified version of the Cochrane treatment
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