Effect of S-Ketamine on Hyperalgesia After Staged Bilateral Arthroplasty: A Randomized Controlled Trial

INTERVENTION: Experimental Group (esketamine):First operation: After venous access was established, the patient underwent neuraxial anesthesia (spinal anesthesia combined with epidural anesthesia) plus saphenous nerve block. Ten minutes before skin incision, the investigator infused esketamine solution prepared by the pharmacy team at a constant rate of 0.1 mL/(kg·h), equivalent to 0.20 mg/(kg·h). The infusion duration was 1 h. If the operation duration was less than 1 h, the study drug was continued in the anesthesia recovery unit and completed before initiation of PCIA. Esketamine was prepared by standard dilution: 50 mg esketamine was added to 0.9% normal saline and diluted to 25 mL, with a total concentration of 2 mg/mL. Postoperative routine PCIA (patient‐controlled intravenous analgesia): sufentanil 1.5 µg/kg + esketamine 1 mg/kg (calculated by actual body weight) + ondansetron 8 mg, diluted in 0.9% sodium chloride injection to a total volume of 100 mL. Background dose 1 mL/h, PCA dose 2 mL per time, lockout time 15 min, continuous use for 48 h. Second operation: Equal volume of 0.9% normal saline was used instead of esketamine intraoperatively and postoperatively. The simulated infusion maintained the same appearance, operation and sound prompts of the infusion pump to maintain blinding. PCIA formula: sufentanil 1.5 µg/kg + ondansetron 8 mg, diluted in 0.9% sodium chloride injection to a total volume of 100 mL. Other parameters and analgesic measures were the same as those in the first operation.;Control Group (normal saline):First operation and second operation: An equal volume of 0.9% sodium chloride injection was used instead of esketamine intraoperatively and postoperatively. The PCIA formulation was sufentanil 1.5 µg/kg + ondansetron 8 mg, diluted in 0.9% sodium chloride CONDITION: Postoperative pain PRIMARY OUTCOME: Area under the curve of mechanical pain threshold at 6, 12, 24, 48, and 72 hours after the second operation.; SECONDARY OUTCOME: Area under the curve of mechanical pain threshold at 6, 12, 24, 48, and 72 hours after the first operation.;Incidence of mechanical allodynia at 24 hours after surgery;Mechanical pain threshold before the second operation;Incidence of central sensitization;NRS pain score;Cumulative postoperative opioid consumption;Extra rescue analgesic dosage;Incidence of rebound pain;Quality of Recovery‐15 (QoR‐15) score;Sleep quality;Time to first patient‐controlled analgesia (PCA) bolus;Incidence of chronic postsurgical pain (CPSP);Hospitalization cost;Postoperative length of hospital stay; INCLUSION CRITERIA: 1. Age 18‐75 years old; 2. ASA classification Grade I‐III; 3. To be scheduled for staged bilateral total knee arthroplasty under spinal anesthesia on an elective basis within one year; 4. Patients voluntarily participate in this study and sign the informed consent form.