Study Summary

225 patients with traumatic lower limb fractures were randomized to receive low-dose esketamine 0.5 mg/kg, high-dose esketamine 0.75 mg/kg, or saline placebo (control), each in addition to standardized sufentanil-based postoperative analgesia. The primary outcomes were the Hamilton Depression Rating Scale (HAMD) scores assessed preoperatively and on postoperative days 1, 3, and 7, and total postoperative sufentanil consumption over 48 hours. Secondary outcomes included Visual Analog Scale (VAS) pain scores, Patient-Controlled Analgesia (PCA) compressions, Ramsay sedation scores, serum Brain-Derived Neurotrophic Factor (BDNF) and Interleukin-6 (IL-6) levels at 24 and 48 hours, and adverse events. Outcomes were assessed up to 7 days postoperatively. Overall, the results revealed significantly lower HAMD scores on postoperative days 1 and 3 in both esketamine groups vs. control, with greater reduction in the high-dose group on day 3, alongside significantly reduced sufentanil consumption and PCA compressions. Continuous postoperative esketamine infusion effectively improved early postoperative depressive symptoms and achieved an opioid-sparing effect without increasing major adverse events.