Ondansetron: recommended antiemetics for patients with acute pancreatitis? a population-based study

**Background:** Acute pancreatitis (AP) affects approximately 20% of patients who develop moderate-to-severe disease with high fatality rates. Nausea and vomiting are common symptoms that can lead to fluid loss and delayed enteral nutrition. Ondansetron, a selective 5-HT3 receptor antagonist, is widely used as an antiemetic and has shown anti-inflammatory effects in preclinical models, including reduced pancreatic injury in cerulein-induced AP in mice. However, no retrospective clinical study had analyzed ondansetron's effects on multiple outcomes in ICU patients with AP.

**Methods:** This retrospective cohort study used the MIMIC-IV database (v2.0), which contains data from 315,460 patients at Beth Israel Deaconess Medical Center (2008–2019). From 6,195 hospitalization records of patients with acute pancreatitis, 1,030 first ICU admissions were included after exclusions. Patients were divided into the ondansetron administration group (OND, n=663) and non-ondansetron group (non-OND, n=367). Variables included demographics, comorbidities, interventions (RRT, mechanical ventilation), vital signs, and laboratory tests within the first 24 hours. Outcomes were in-hospital survival, 90-day prognosis, and overall prognosis. Statistical methods included Kaplan-Meier survival analysis with log-rank tests, multivariate Cox proportional hazards models, inverse probability of treatment weighting (IPTW), time-dependent covariate analysis, and restricted cubic spline (RCS) analysis for dose-response relationships.

**Key Results:** The OND group had significantly better outcomes across all measures. In-hospital mortality was 11.1% (74/663) in the OND group versus 16.0% (59/367) in the non-OND group. 90-day mortality was 15.6% (104/663) versus 23.1% (85/367). Overall survival at end of follow-up was 29.8% vs. 37.3% (p=0.009). In the multivariate Cox model, ondansetron was an independent prognostic factor for in-hospital (HR: 0.50, 95% CI: 0.34–0.74, p=0.001), 90-day (HR: 0.63, 95% CI: 0.46–0.86, p=0.004), and overall (HR: 0.66, 95% CI: 0.52–0.84, p=0.001) survival. These results were confirmed in IPTW-matched and time-dependent covariate analyses. RCS analysis identified optimal minimum doses of 7.8 mg (in-hospital), 4.9 mg (90-day), and 4.6 mg (overall) for maximum survival benefit. Timing of first ondansetron administration was not statistically associated with outcomes. Ondansetron's benefits remained stable and were significantly superior to other antiemetics (metoclopramide, diphenhydramine, prochlorperazine) when included in the same model.

**Clinical Implications:** This study provides the first clinical evidence that ondansetron administration is associated with improved survival outcomes in ICU patients with acute pancreatitis. The recommended minimum total dose of 4–8 mg appears sufficient to achieve near-maximum benefit, with higher doses potentially increasing risk of QTc prolongation without additional survival advantage. The findings support ondansetron as the preferred antiemetic for ICU AP patients with nausea and vomiting, though the authors acknowledge limitations including retrospective design, inability to determine cause of death, and lack of side effect data. Prospective randomized trials are needed to confirm these findings.