Ondansetron Oral Soluble Pellicles Effectively Reduce the Incidence of Postoperative Nausea and Vomiting Following Primary Total Joint Arthroplasty: A Randomized Controlled Trial

BACKGROUND: Ondansetron is a cornerstone medication for preventing postoperative nausea and vomiting (PONV) in numerous international guidelines. Ondansetron oral soluble pellicles (OSP) represent a needle-free PONV prophylaxis administration regimen with favorable practicality. We conducted this study to investigate the optimal dosing regimen by comparing the efficacy and safety of different doses of ondansetron OSP for preventing PONV following total joint arthroplasty (TJA). METHODS: This is a randomized, controlled, and double-masked clinical trial. A total of 198 patients were randomized into three groups: the control group receiving two placebo pellicles orally 1 hour before anesthesia induction; the preoperation (Preop) 8-mg group receiving one ondansetron OSP (8 mg) plus one placebo pellicles; and the Preop 16-mg group receiving two ondansetron OSP (16 mg total). The primary outcome was the incidence and severity (measured by visual analog scale scores) of PONV within 48 hours after TJA. The secondary outcome included the frequency of tramadol and metoclopramide and the occurrence of ondansetron adverse drug reactions. RESULTS: Both 8 and 16 mg ondansetron OSP markedly reduced PONV incidence. Compared with the Preop 8-mg group, the Preop 16-mg group demonstrated markedly lower PONV incidence and reduced nausea severity at all postoperative time points relative to the control group, with a greater absolute risk reduction, indicating superior prophylactic efficacy. Adverse drug reactions rates did not differ markedly between the groups. CONCLUSIONS: Compared with placebo, ondansetron OSP effectively reduces the incidence of PONV following TJA and demonstrates a favorable safety profile. The findings suggest a trend toward better efficacy with a preoperative oral dose of 16 mg compared with 8 mg. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500097588. Registered on 21 February 2025.