Authors: Zhu Y et al.
Anesthesiology, January 2026, volume 144, issue 1, pages 63–76
This randomized controlled trial evaluated whether S-ketamine reduces postoperative delirium (POD) in elderly patients undergoing total hip or knee arthroplasty when administered outside a general anesthesia setting. Prior studies suggested potential neuroprotection from ketamine, but effects may have been blunted by general anesthesia. To isolate this question, the investigators studied 372 elderly patients receiving neuraxial anesthesia only, randomized to S-ketamine or placebo. Delirium assessments were performed daily for three postoperative days using standardized diagnostic tools, with careful tracking of pain, opioid use, sleep quality, and adverse effects.
Postoperative delirium occurred in 8.1% of patients receiving S-ketamine compared with 20.4% in the placebo group, representing a substantial and statistically significant reduction in risk. Patients in the S-ketamine group experienced fewer delirium episodes and earlier resolution when POD occurred. Pain scores during activity and physical therapy on postoperative day 1 were lower, and fewer patients required rescue analgesia. Total opioid consumption was modestly reduced. However, S-ketamine was associated with a higher incidence of transient neuropsychiatric side effects, including hallucinations, dizziness, and nightmares. Serious adverse events were uncommon and similar between groups.
The authors conclude that S-ketamine meaningfully reduces postoperative delirium when administered under neuraxial anesthesia, suggesting that anesthetic context strongly influences ketamine’s neurocognitive effects. While the findings are compelling, they caution that results may not generalize to institutions without standardized perioperative pathways or to patients receiving general anesthesia.
Key Points
S-ketamine significantly reduced postoperative delirium in elderly arthroplasty patients under neuraxial anesthesia.
Avoidance of general anesthesia may unmask ketamine’s neuroprotective effects.
Pain during early mobilization and need for rescue analgesia were reduced.
Neuropsychiatric side effects were more common but generally mild and transient.
Applicability may be limited to centers with high protocol adherence.
Thank you to Anesthesiology for allowing us to summarize and discuss this important work.