Research Summary

Multidose Ondansetron After Pediatric ED Discharge Reduces Gastroenteritis Severity

Miranda Manier, BA

Key Highlights:

  • Postdischarge multidose ondansetron reduced moderate-to-severe gastroenteritis versus placebo (5.1% vs 12.5%; risk difference, −7.4 percentage points; 95% CI, −11.2 to −3.7).
  • Primary outcome favored ondansetron after adjustment (adjusted odds ratio [aOR], 0.50; 95% CI, 0.40–0.60).
  • Fewer total vomiting episodes within 48 hours with ondansetron (adjusted rate ratio, 0.76; 95% CI, 0.67–0.87), without meaningful differences in presence or median duration of vomiting.
  • No substantial between-group differences in unscheduled visits, intravenous fluid receipt, or adverse events (odds ratio, 0.99; 95% CI, 0.61–1.61).

In a multicenter, double-blind, randomized superiority trial of children presenting to pediatric emergency departments with acute gastroenteritis–associated vomiting, provision of ondansetron to be used at home after discharge was associated with a lower risk of moderate-to-severe gastroenteritis during the week after enrollment compared with placebo. Although ondansetron did not change whether vomiting occurred or its median duration, it reduced the total number of vomiting episodes within the first 48 hours.

Ondansetron given in the emergency department is known to improve outcomes for children with gastroenteritis-related vomiting. Despite its common prescription at discharge to mitigate ongoing symptoms, robust evidence supporting postdischarge, multidose use has been limited, prompting this trial.

Children 6 months to 18 years of age were enrolled across six pediatric emergency departments and randomly assigned to receive either oral ondansetron or placebo in a double-blind fashion. Caregivers received six doses to administer in response to ongoing vomiting during the first 48 hours after enrollment. The primary outcome was moderate-to-severe gastroenteritis, defined as a modified Vesikari score of 9 or greater (scale, 0–20; higher scores indicate greater severity) during the 7 days following enrollment. Secondary outcomes included presence of vomiting, duration of vomiting (time from enrollment to last episode), number of vomiting episodes within 48 hours, unscheduled physician visits within 7 days, and receipt of intravenous fluids.

Among 1030 randomized participants, moderate-to-severe gastroenteritis occurred in 5.1% (23/452 with available data) in the ondansetron group versus 12.5% (55/441) in the placebo group, yielding an unadjusted risk difference of −7.4 percentage points (95% CI, −11.2 to −3.7). After adjustment for site, weight, and missing data, ondansetron remained associated with a lower risk of the primary outcome (aOR, 0.50; 95% CI, 0.40–0.60). Although there was no meaningful difference between groups in the presence or median duration of vomiting, the total number of vomiting episodes within 48 hours after enrollment was lower with ondansetron than with placebo (adjusted rate ratio, 0.76; 95% CI, 0.67–0.87). The proportions with unscheduled health care visits and those receiving intravenous fluids over the subsequent week did not differ substantially between groups. Adverse event incidence was similar (odds ratio, 0.99; 95% CI, 0.61–1.61).

“Among children with gastroenteritis-associated vomiting, the provision of ondansetron after an emergency department visit led to lower risk of moderate-to-severe gastroenteritis during the subsequent 7 days than the provision of placebo,” Stephen B. Freedman, MDCM, and colleagues concluded.

Reference:
Freedman SB, Williamson-Urquhart S, Plint AC, et al. Multidose ondansetron after emergency visits in children with gastroenteritis. N Engl J Med. 2025;393(3):255-266. doi:10.1056/NEJMoa2503596