Authors: Zhu Y. et al.
Anesthesiology, October 14, 2025. DOI: 10.1097/ALN.0000000000005800
This randomized controlled trial investigated whether S-ketamine reduces postoperative delirium (POD) in elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia—avoiding the potential confounding effects of general anesthesia on ketamine’s neuroprotective properties. Conducted at a high-volume arthroplasty center with rigorous perioperative standardization, the study enrolled 372 patients aged 65 years and older who were randomized to receive either S-ketamine or placebo during surgery.
Within three postoperative days, the incidence of POD was significantly lower in the S-ketamine group (8.1%) compared to the placebo group (20.4%), corresponding to an adjusted odds ratio of 0.29 (95% CI, 0.14–0.63; P = 0.002). S-ketamine recipients also reported less pain during mobilization and required fewer rescue analgesics on postoperative day one. Although adverse events such as hallucinations, dizziness, and nightmares occurred more frequently with S-ketamine, these effects were transient and mild.
These results indicate that when used under neuraxial (non-general) anesthesia, S-ketamine confers substantial protection against POD while simultaneously enhancing postoperative analgesia. The study suggests that previous trials conducted under general anesthesia may have underestimated S-ketamine’s cognitive benefits due to anesthetic interactions that suppress its neuroprotective mechanisms.
What You Should Know
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S-ketamine significantly reduced postoperative delirium from 20% to 8% in elderly arthroplasty patients under neuraxial anesthesia.
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Benefits included lower pain scores and reduced need for rescue analgesia.
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Mild psychotropic effects (hallucinations, dizziness) were more common but transient.
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The study reinforces the importance of anesthetic context—neuraxial anesthesia may allow S-ketamine’s neuroprotective effects to manifest more fully.
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Larger multicenter studies are needed to confirm generalizability beyond high-volume, protocol-driven centers.
Thank you to Anesthesiology for publishing this pivotal trial clarifying S-ketamine’s role in preventing postoperative delirium in elderly orthopedic patients.