S-Ketamine Reduces the Risk of Rebound Pain in Patients Following Total Knee Arthroplasty: A Randomized Controlled Trial.

Purpose: Investigating the effectiveness of S-ketamine in reducing rebound pain (RP) following total knee arthroplasty.

Patients and methods: This study was a randomized, double-blind, placebo-controlled trial involving 356 adult patients undergoing total knee arthroplasty. Patient enrollment occurred between April and October 2023, with in-person follow-up assessments conducted from admission to 3 days post-surgery. Participants were randomly assigned to the S-ketamine group (n = 178) and the placebo group (n = 178). In the S-ketamine group, participants received a continuous intraoperative infusion of S-ketamine at a dose of 0.30 mg/(kg·h) from the completion of spinal anesthesia until the beginning of joint cavity closure, whereas the placebo group received a continuous infusion of 0.9% saline at the same volume and duration. The primary outcome was the incidence of RP within 12 hours post-surgery. Secondary outcomes included the incidence of RP within 24 hours, time to RP onset, time to first rescue analgesia, pain scores, opioid consumption, clinical outcomes, and harms.

Results: RP was observed in 21.3% of patients in the S-ketamine group compared with 34.8% in the placebo group within 12 hours post-surgery (adjusted RR, 0.62; 95% CI, 0.44 to 0.88; P = 0.008). The onset of RP was significantly delayed in the S-ketamine group compared with the placebo group (unadjusted HR, 0.60; 95% CI, 0.41 to 0.88; P = 0.009). The numerical rating scale during activity and physical therapy was lower in the S-ketamine group than in the placebo group (day 1 AM: unadjusted difference, -1; 95% CI, -1 to 0; P = 0.011; day 1 PM: unadjusted difference, -1; 95% CI, -1 to 0; P = 0.003; day 1 physical therapy: unadjusted difference, -2; 95% CI, -2 to -1; P < 0.001). The quality of recovery score was higher in the S-ketamine group than in the placebo group (unadjusted difference, 5; 95% CI, 5 to 5; P < 0.001). Patient satisfaction was higher in the S-ketamine group than in the placebo group (unadjusted difference, 1; 95% CI, 1 to 1; P < 0.001).

Conclusions: S-ketamine effectively reduces the risk of rebound pain and delays its onset in total knee arthroplasty. Additionally, S-ketamine can reduce early pain levels, enhance recovery quality, and improve patient satisfaction.