Effectiveness of Perioperative S-ketamine on Postoperative Pain in Patients with Osteoarthritis Undergoing Total Knee Arthroplasty

Corresponding author: DAI Hongyu, daihy0326@163.com

DOI: 10.12201/bmr.202607.00018

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  Abstract: Objective To investigate the effect of perioperative S-ketamine intervention on postoperative pain in patients undergoing total knee arthroplasty (TKA) and to explore the moderating effects of preoperative central sensitization, anxiety, depression, and pain-related risk factors on the intervention efficacy. MethodsSA total of 124 patients with knee osteoarthritis scheduled for unilateral TKA between December 2024 and March 2026 were enrolled. Patients aged 60–75 years, with American Society of Anesthesiologists (ASA) grade Ⅰ–Ⅱ, body mass index (BMI) 18–30 kg/m2, were randomly divided into a control group (n=61) and an S-ketamine group (n=63). The S-ketamine group received an intravenous loading dose of S-ketamine 0.3 mg/kg after anesthesia induction, followed by continuous infusion via patient-controlled intravenous analgesia (PCIA) at a rate of 0.015 mg/kg.h until 48 h postoperatively. The control group received an equal volume of normal saline. Pain intensity was assessed using the Visual Analogue Scale (VAS). The primary outcome was the incidence of moderate-to-severe pain within 48 h postoperatively. Secondary outcomes included pain scores at various postoperative time points, rate of rescue analgesia within 48 h postoperatively, medication-related adverse reactions, and quality of recovery. Subgroup analyses were performed to evaluate the interaction between preoperative risk factors and the efficacy of S-ketamine. ResultsSThe incidence of moderate-to-severe pain within 48 h postoperatively (15.87% vs. 36.07%, adjusted OR = 0.194, 95% CI: 0.060–0.629, adjusted P = 0.006) and the rate of rescue analgesia were significantly lower in the S-ketamine group than in the control group. The VAS scores in the S-ketamine group were lower than those in the control group at 12–24 h postoperatively, but the reduction did not reach the minimum clinically important difference threshold. The quality of recovery score was higher in the S-ketamine group than in the control group. The incidence of delayed emergence was higher in the S-ketamine group. Subgroup analysis revealed that preoperative central sensitization significantly moderated the efficacy of S-ketamine (P for interaction = 0.026). Among patients with preoperative central sensitization, the incidence of moderate-to-severe pain was significantly lower in the S-ketamine group than in the control group (6.9% vs. 50.0%, OR = 0.074, P = 0.003). ConclusionSPerioperative S-ketamine reduces the incidence of moderate-to-severe pain and the need for rescue analgesia following TKA, and improves postoperative quality of recovery; however, it is associated with a risk of delayed emergence and lacks clinically significant improvement in pain scores. Subgroup analysis suggests that stratified intervention based on preoperative central sensitization status may be an effective strategy to optimize perioperative pain management in TKA.

  Key words: STotal; knee arthroplasty, S-ketamine, Pain, Central; sensitization; 

  Submit time: 8 July 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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