The Analgesic Effect of Low-Dose S(+)-Ketamine in Knee Joint Replacement: A Randomized Controlled Trial.

Background: Insufficient pain relief during knee joint replacement surgery can have adverse effects on the postoperative recovery of the patient. In this study, we evaluated the analgesic effect of intravenous infusion of low-dose S(+)-ketamine in patients following knee joint replacement surgery. Methods: This study was a randomized, single-blind, placebo-controlled trial involving 144 patients who underwent knee joint replacement. Patients were randomly assigned to receive an intravenous infusion of S(+)-ketamine (0.3 mg/kg/h) or 0.9% sodium chloride solution. The primary efficacy endpoint was evaluated based on NRS scores at 2 h, 24 h, and 48 h after surgery. Additionally, the intraoperative doses of sufentanil, propofol, and remifentanil were investigated. The number of patients who required analgesic rescue and the number of patients who experienced adverse reactions within 48 h postoperatively were recorded. Results: S(+)-ketamine reduced NRS scores for movement pain at 2 h [2.36 ± 0.66 vs 3.1 ± 0.65, P < 0.001], 24 h [2.15 ± 0.62 vs 2.79 ± 0.85, P < 0.001], and 48 h [1.81 ± 0.6 vs 2.29 ± 0.76, P < 0.001] postoperatively. Administering S(+)-ketamine reduced the dose of sufentanil [30 (30, 35) vs 40 (35, 40), P < 0.001] but not propofol [333.68 ± 75.02 vs 323.06 ± 79.94, P = 0.412] or remifentanil [1.8 (1.4, 2.2) vs 1.6 (1.325, 2), P = 0.131]. The use of intraoperative S(+)-ketamine significantly reduced the patient proportion of requiring additional analgesics postoperatively (4.2% vs 19.4%, P = 0.004). A lower incidence of dizziness (1.4% vs 12.5%, P = 0.009), nausea (11.1% vs 29.2%, P < 0.001), and vomiting (8.3% vs 29.2%, P = 0.001) was found in patients treated with S(+)-ketamine (P < 0.05). Conclusion: Intravenous infusion of S(+)-ketamine during surgery of elderly patients undergoing knee joint replacement can alleviate postoperative acute pain, providing research support for the application of S(+)-ketamine in multimodal analgesia. Trial Registration: NCT05289050.