Authors: Kim K et al.
Anesthesia & Analgesia, 2026.
Effect of Amisulpride Inclusion in a Postoperative Nausea and Vomiting Protocol: A Retrospective Pre–Post Analysis.
This research letter evaluated the effect of adding amisulpride to an institutional postoperative nausea and vomiting (PONV) prevention protocol. Although numerous antiemetic agents are available, evidence comparing rescue strategies after failed prophylaxis remains limited. Current PONV guidelines recommend using agents with different receptor mechanisms when treating breakthrough nausea and vomiting.
Amisulpride is a dopamine D₂/D₃ receptor antagonist that has recently been approved for rescue treatment of PONV after prophylactic therapy fails. The investigators sought to determine whether incorporating amisulpride into a clinical protocol would reduce the need for second-line antiemetic therapy.
The study was a retrospective cohort analysis conducted at a single institution. Adult patients undergoing cancer surgery with general anesthesia at an ambulatory center between October 2017 and April 2023 were included.
A protocol change occurred in June 2022. Before this change, ondansetron was used as the primary rescue antiemetic. After implementation of the revised protocol, amisulpride (10 mg) replaced ondansetron as the first-line rescue therapy. Droperidol was removed from the protocol due to concerns about sedation.
The analysis included 13,926 adult patients who underwent 16,341 ambulatory procedures. Two protocol periods were compared:
• Pre-protocol period: October 2017 to May 2022
• Post-protocol period: August 2022 to April 2023
The primary outcome was the need for a second-line antiemetic. The investigators hypothesized that the revised protocol would reduce the proportion of patients requiring additional treatment for PONV.
Statistical analyses included multivariable logistic regression adjusting for multiple patient and procedural factors known to influence PONV risk. These included Apfel risk score, American Society of Anesthesiologists physical status, surgical service, opioid exposure (intraoperative oral morphine equivalents), use of total intravenous anesthesia, perioperative midazolam use, and other antiemetics.
The revised protocol incorporating amisulpride was associated with a lower likelihood of requiring a second-line antiemetic. This finding suggests improved control of breakthrough PONV when amisulpride is used as the initial rescue therapy.
The study also examined secondary outcomes, including extended postoperative stay due to PONV lasting longer than six hours.
The authors conclude that incorporating amisulpride into a rescue antiemetic protocol may improve management of postoperative nausea and vomiting after ambulatory surgery. The findings support guideline recommendations to use antiemetics targeting different receptor pathways when treating breakthrough PONV.
However, the authors note several limitations. The study was retrospective and observational, meaning that causation cannot be definitively established. Additionally, protocol changes occurred over time, which may introduce confounding from evolving clinical practices.
Future prospective studies may help clarify the optimal role of amisulpride within multimodal PONV prevention and rescue strategies.
Key Points
• Amisulpride is a dopamine receptor antagonist approved for rescue treatment of postoperative nausea and vomiting.
• This study evaluated the effect of adding amisulpride to an institutional PONV protocol.
• More than 13,000 ambulatory cancer surgery patients were included in the analysis.
• Replacing ondansetron with amisulpride as first-line rescue therapy reduced the need for second-line antiemetics.
• The findings support using different receptor-targeted antiemetics for breakthrough PONV.
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