{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:33:18Z","timestamp":1793295198338,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The widespread use of high-dose antifibrinolytic agents (tranexamic acid) and opioids in total joint arthroplasty (TJA) has highlighted a critical concern: postoperative nausea and vomiting (PONV). Ondansetron, recognized as a cornerstone medication for PONV prevention in clinical guidelines, offers an innovative solution through its oral soluble pellicle (OSP) formulation. We conducted this study to investigate the optimal dosing regimen of ondansetron OSPs for preventing PONV following primary TJA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized, controlled, double-masked clinical trial allocated 198 patients to three intervention groups: (1) Preop 16\u202fmg group: Two ondansetron OSPs (16\u202fmg) administered orally 1\u202fh before induction, followed by placebo films at 6 and 12\u202fh postoperatively; (2) 16\u202f+\u202f8\u202fmg group: Two ondansetron OSPs (16\u202fmg) administered preoperatively, followed by one ondansetron OSP (8\u202fmg) at 6\u202fh and one placebo film at 12\u202fh postoperatively; (3) 8\u202f+\u202f8\u202f+\u202f8\u202fmg group: One ondansetron OSP (8\u202fmg) and one placebo film administered preoperatively, followed by one ondansetron OSP (8\u202fmg) at both 6 and 12\u202fh postoperatively. The primary outcome assessed the incidence and severity of PONV within 48\u202fh after TJA. Secondary outcomes included the utilization frequency of rescue metoclopramide and tramadol, along with adverse drug reactions (ADRs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The primary outcomes demonstrated that both the Preop 16\u202fmg and 16\u202f+\u202f8\u202fmg groups achieved significantly lower incidences of postoperative nausea compared to the 8\u202f+\u202f8\u202f+\u202f8\u202fmg group, although no statistically significant differences were observed among the three groups in nausea severity (visual analog scale (VAS) scores) or postoperative vomiting frequency. The secondary outcomes showed significantly reduced metoclopramide utilization in the 16\u202f+\u202f8\u202fmg group versus the 8\u202f+\u202f8\u202f+\u202f8\u202fmg group, with a non-significant trend in the Preop 16\u202fmg group, while tramadol usage and ADR rates showed no significant intergroup differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared to the 8\u202f+\u202f8\u202f+\u202f8\u202fmg regimen, both the Preop 16\u202fmg and 16\u202f+\u202f8\u202fmg dosing strategies demonstrated superior efficacy. For high-risk patients, the 16\u202f+\u202f8\u202fmg regimen may represent the optimal therapeutic approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1702879","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T06:33:54Z","timestamp":1764830034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Optimal dosing regimen of ondansetron oral soluble pellicles for preventing postoperative nausea and vomiting after primary total joint arthroplasty: a randomized controlled clinical trial"],"prefix":"10.3389","volume":"12","author":[{"given":"Yinghao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangjie","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongke","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.joca.2022.01.012","article-title":"Surgical therapy in osteoarthritis","volume":"30","author":"Madry","year":"2022","journal-title":"Osteoarthr 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anesthesia: a randomized, double-blinded clinical trial","volume":"20","author":"Xie","year":"2020","journal-title":"BMC Anesthesiol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40360-024-00735-9","article-title":"Comparison of three different prophylactic treatments for postoperative nausea and vomiting after total joint arthroplasty under general anesthesia: a randomized clinical trial","volume":"25","author":"Xie","year":"2024","journal-title":"BMC Pharmacol Toxicol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0186006","DOI":"10.1371\/journal.pone.0186006","article-title":"Comparative efficacy of ramosetron and ondansetron in preventing postoperative nausea and vomiting: an updated systematic review and meta-analysis with trial sequential analysis","volume":"12","author":"Yokoi","year":"2017","journal-title":"PLoS 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