Clinical Evaluation of the Efficacy and Safety of Ondansetron in Pediatric Acute Gastroenteritis: A Systematic Review of Clinical Profiles, Healthcare Utilization, and Hospital Outcomes

Acute gastroenteritis (AGE) is a common cause of morbidity in children, and vomiting is often an obstacle to effective oral rehydration therapy (ORT). This systematic review aimed to assess the efficacy and safety of ondansetron in treating AGE in children. PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to June 2026. We used Zotero for reference management and duplicate removal and Rayyan for study screening. Risk of bias was assessed using the Cochrane Risk of Bias 2 for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for retrospective cohort studies. Due to methodological diversity across studies, a qualitative narrative synthesis was performed. Eight studies comprising 60,191 participants were included, including five RCTs with 2,397 participants and three retrospective cohort studies with 57,794 participants. Among RCTs, ondansetron consistently reduced vomiting compared with placebo or usual care. In one large randomized trial, ondansetron was associated with fewer vomiting episodes within 48 hours (adjusted rate ratio, 0.76; 95% CI, 0.67-0.87), while another randomized trial reported a lower occurrence of moderate-to-severe disease (5.1% vs. 12.5%; adjusted OR, 0.50; 95% CI, 0.40-0.60). The need for IV fluids was also reduced in randomized evidence, with one trial reporting rates of 14% vs. 31% (RR, 0.46; 95% CI, 0.26-0.79). Observational cohort studies provided less consistent evidence regarding healthcare utilization outcomes. Hospitalization rates were 2.0% vs. 10.0% in one cohort and 6.3% vs. 7.2% in another, while ED revisits varied across studies, including rates of 4.0% vs. 4.8% at 72 hours in one cohort (adjusted OR, 0.82; 95% CI, 0.72-0.95), with nonsignificant differences reported in other studies. Regarding safety, one randomized trial reported similar adverse-event rates between ondansetron and placebo (7.0% vs. 7.1%; OR, 0.99; 95% CI, 0.61-1.61), although repeated dosing was associated with more mild diarrhea (rate ratio, 1.36; 95% CI, 1.03-1.80). Overall, the randomized evidence supports ondansetron as an effective adjunct to ORT for reducing vomiting and IV fluid requirements in children with AGE, while observational evidence regarding hospitalization and ED revisits was inconsistent. Because no quantitative meta-analysis was performed, these estimates represent findings from individual studies rather than pooled effects. Further high-quality multicenter studies using standardized outcomes are needed to clarify the effects of ondansetron on healthcare utilization and longer-term safety.