TOPLINE:

In older adults undergoing total hip or knee arthroplasty under neuraxial anesthesia, receiving S-ketamine was associated with a reduced risk for postoperative delirium within the first 3 days after the procedure. The level of pain and the need for rescue analgesia were lower in patients receiving S-ketamine than in those receiving a placebo.

METHODOLOGY:

• Researchers conducted a randomized controlled trial in China from November 2023 to October 2024 to evaluate the effect of S-ketamine on the risk for postoperative delirium in 372 older adults undergoing total hip or knee arthroplasty under neuraxial anesthesia.
• Participants were randomly assigned to receive an intravenous infusion of either 2 mg/mL S-ketamine in normal saline at a rate of 0.1 mL/kg/h for 1 hour (n = 186; median age, 67 years; 63% women) or a placebo containing normal saline (n = 186; median age, 68 years; 66% women).
• In the postanesthesia care unit, the patient-controlled intravenous analgesia devices for the S-ketamine group contained 1 mg/kg S-ketamine, 50 μg sufentanil, and 8 mg ondansetron. The placebo group received the same components, excluding S-ketamine. Both groups received analgesia for 48 hours.
• The primary outcome was the risk for postoperative delirium within 3 days post-surgery, assessed twice daily starting 6 hours after surgery using a version of 3D-CAM.
• Secondary outcomes included pain scores, consumption of opioids, and quality of sleep.

TAKEAWAY:

• The incidence of postoperative delirium was lower in the S-ketamine vs placebo group in the 3 days following surgery (8.06% vs 20.43%; adjusted odds ratio, 0.29; P = .002).
• Patients in the S-ketamine group experienced less pain during exercise and physical therapy on the first postoperative day than those in the placebo group.
• The proportion of patients requiring rescue analgesia on the first postoperative day was lower in the S-ketamine vs placebo group, with 37 vs 54 patients requiring the pain medication.
• Higher proportions of patients in the S-ketamine group than in the placebo group reported nightmares (P = .022), dizziness (P = .001), and hallucinations (P = .001).

IN PRACTICE:

“S-ketamine can reduce risk of [postoperative delirium] in elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. However, generalizability of these findings may be limited due to the study’s setting,” the researchers reported. 

SOURCE:

The study was led by Youzhuang Zhu, MD, PhD, of the Shandong Provincial Key Medical and Health Laboratory of Anesthesia and Brain Function at the Affiliated Hospital of Qingdao University in Qingdao, China. It was published online on October 14, 2025, in Anesthesiology.

LIMITATIONS:

The number of patients undergoing total hip arthroplasty with neuraxial anesthesia was small. The postoperative analgesia protocol followed routine practices of the center, which may differ from other guidelines. The lack of routine sedation in the placebo group does not reflect real-world clinical scenarios. The findings may not apply to other settings due to the single-center design and specific setting.

DISCLOSURES:

This study was supported by grants from the Youth Research Fund of Qingdao University, Intramural Research Program of the Affiliated Hospital of Qingdao University, Qingdao Key Medical and Health Discipline Project, Qingdao Leading Discipline Program in Medicine and Health, Shandong Provincial Medical and Health Science and Technology Guidance Project, and Shandong Provincial Natural Science Foundation. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.