Naunyn-Schmiedeberg's archives of pharmacologyJan 3, 2026

Low-dose S-ketamine may prevent confusion after surgery and lower inflammation in older hip fracture patients

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

The S-ketamine group had a lower incidence of postoperative delirium (POD) at 9.6% compared to 29.8% in the control group (P < 0.001).

S-ketamine administration is associated with a reduction in the incidence of POD in older patients undergoing hip fracture surgery.
Patients receiving S-ketamine reported improved sleep quality as indicated by lower Pittsburgh Sleep Quality Index scores from surgery day to day 3 after surgery.
No significant differences were observed in pain levels or analgesic requirements between the S-ketamine and control groups.
The S-ketamine group exhibited lower levels of proinflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, compared to the control group.
Fewer patients in the S-ketamine group experienced nausea and vomiting than in the control group, indicating a better tolerance to the treatment.

Simplified

The preventive effect of S-ketamine on postoperative delirium (POD) in older patients receiving elective surgery is controversial. This randomized, controlled study aimed to evaluate the effect of subanesthetic S-ketamine on the incidence of POD in older patients receiving hip fracture surgery. Three hundred and fifty-six older patients scheduled for elective hip fracture surgery were randomized to S-ketamine group (N = 178, received S-ketamine 0.3 mg/kg loading, 0.2 mg/kg/h infusion) and control group (N = 178, received normal saline with an equal volume). The S-ketamine group showed a lower incidence of POD within 7 days than the placebo group (9.6% versus 29.8%, P < 0.001). Compared with the control group, the S-ketamine group had a lower Pittsburgh Sleep Quality Index score from the surgery day (D0) to day (D)3 after surgery (all P < 0.001). However, pain at rest and at motion (assessed by numerical rating scale) until D2, as well as patient-controlled intravenous analgesic bolus and rescue analgesic within 48 h, were not different between groups. Additionally, the S-ketamine group showed lower proinflammatory cytokines from D0 to D3, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, compared with the control group (all P < 0.01). Moreover, the S-ketamine group disclosed a lower incidence of nausea and vomiting than the placebo group (6.7% versus 28.1%, P < 0.001); the other adverse reactions were comparable between the two groups. S-ketamine at a subanesthetic dose effectively prevents POD and improves sleep quality, with a good safety profile in older patients receiving hip fracture surgery.

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Funding

Competing interests

Declarations. Ethics approval: The study had approval from the Ethics Committee of Handan Central Hospital (batch number: 20240220). Each patient signed the informed consent. Competing interests: The authors declare no competing interests.

PubMed

Low-dose S-ketamine may prevent confusion after surgery and lower inflammation in older hip fracture patients

Abstract

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Abstract

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