Effect of esketamine on postoperative depression and anxiety in patients undergoing cardiac valve surgery: A randomised, placebo-controlled, double-blinded clinical trial

This randomized, double-blind, parallel-group trial evaluated the efficacy of a single intravenous dose of esketamine (0.3 mg/kg) administered at anesthesia induction in reducing postoperative depression and anxiety among patients undergoing cardiac valve surgery. A total of 142 patients from three centers were randomly assigned to receive esketamine or saline. The primary outcomes were the prevalence of depression and anxiety at postoperative day (POD) 7, assessed by the Hospital Anxiety and Depression Scale (HADS). Key secondary outcomes included delirium incidence, pain and insomnia scores, and quality of recovery. Results showed that the esketamine group had significantly lower rates of depression (7.0 % vs. 31.0 %; P < 0.001) and anxiety (11.3 % vs. 35.2 %; P < 0.001) at POD 7, along with reduced delirium incidence (9.8 % vs. 22.5 %; P = 0.040). Improvements were also observed in pain, sleep, and recovery quality. Mechanistic analyses revealed that esketamine reduced inflammatory markers (IL-6, CRP) and neuronal injury marker (S100β), while increasing brain-derived neurotrophic factor (BDNF). No significant differences in adverse events were observed. In conclusion, a single low dose of esketamine during induction effectively alleviates early postoperative depression and anxiety, possibly through modulating neuroinflammation and promoting neurotrophic signaling. (Clinicaltrials.gov, ID Number: NCT06608030).