Abstract
Vomiting is a leading cause of emergency department (ED) visits among children with acute gastroenteritis (AGE). Although antiemetics are commonly used, uncertainty persists regarding the comparative efficacy and safety of individual agents across clinically relevant timeframes. To compare the efficacy and safety of commonly used antiemetics for pediatric AGE-related vomiting in ED settings using a network meta-analysis (NMA) of randomized controlled trials (RCTs). A systematic search of major databases was conducted through 2025. Eligible studies were RCTs enrolling children ≤21 years presenting to the ED with AGE. Interventions included ondansetron (all routes), dimenhydrinate, domperidone, metoclopramide, bromopride, and placebo. Outcomes included vomiting frequency (short-, intermediate-, and long-term), cessation of vomiting, need for intravenous (IV) rehydration, ED length of stay, hospitalization, and adverse events. A random-effects frequentist NMA was performed. Risk of bias was assessed using ROB-2, and certainty of evidence was evaluated with GRADE. Thirty-three RCTs were included. In the short term, all ondansetron formulations reduced vomiting compared with placebo, with the strongest effect seen with IV administration (MD -1.86, 95% CI -3.25 to -0.47). For intermediate-term outcomes, IV ondansetron was the only agent consistently superior to placebo and active comparators. For long-term vomiting, dimenhydrinate (oral and rectal) demonstrated significant benefit (rectal: MD -0.72, 95% CI -1.14 to -0.30). Vomiting cessation within 24 h favored IV ondansetron (RR 1.56, 95% CI 1.29-1.89), with additional benefit from rectal dimenhydrinate (RR 1.48, 95% CI 1.08-2.04). Ondansetron reduced the need for IV rehydration (RR 0.62, 95% CI 0.44-0.88) and modestly shortened ED stay. Safety comparisons were imprecise, though ondansetron showed fewer adverse events than metoclopramide. Ondansetron provides the most consistent benefit for acute vomiting control and reducing IV fluid use in pediatric AGE, while dimenhydrinate may support longer-term symptom control.