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Nausea shouldn’t be the most memorable part of surgery. We take a clear, evidence-based look at postoperative nausea and vomiting, from identifying who’s at risk to building smarter prophylaxis bundles and choosing the right rescue when prevention falls short. With guest insights from Dr. Connie Chung, we unpack the Fourth Consensus Guidelines, translate them into practical workflows, and explore how Amisulpride—an atypical D2 antagonist—changes the game with an FDA indication for rescue after failed prophylaxis. We start by shrinking baseline risk: consider regional anesthesia when feasible, leverage TIVA with propofol, avoid nitrous and volatiles in longer cases, hydrate well, and spare opioids with multimodal analgesia. Then we scale prophylaxis to risk: dexamethasone at induction, 5-HT3 antagonists at the end, transdermal scopolamine for select patients, and low-dose Droperidol where appropriate. When prophylaxis fails, we explain why repeating ondansetron rarely helps and how switching classes boosts rescue success. Along the way, we map the safety terrain for D2 antagonists—QT prolongation, extrapyramidal risks, anticholinergic effects—so you can individualize care for elderly patients, those on antipsychotics, or anyone with potential drug interactions. We also dig into what’s new: contemporary analyses of Droperidol at antiemetic doses, and growing evidence that Amisulpride pairs well with Ondansetron or Dexamethasone to improve outcomes. Pediatric pearls include TIVA, fluids, and a two-drug prophylaxis backbone for longer or higher-risk cases. The result is a practical, stepwise approach you can apply tomorrow—reduce risk, layer mechanisms, and rescue smartly—to cut PACU delays, avoid unplanned admissions, and deliver a recovery that feels as good as the surgical fix. If this deep dive helps your practice, follow, share with your team, and leave a quick review to help others find the show. Tell us your go-to PONV bundle and whether your site stocks Amisulpride. For show notes & transcript, visit our episode page at apsf.org: https://www.apsf.org/podcast/287-a-ne... © 2025, The Anesthesia Patient Safety Foundation