[Esketamine Alleviates Postoperative Depressive Symptoms in Frail Elderly Patients Undergoing Thoracoscopic Radical Resection of Lung Cancer: A Randomized Double-Blind Controlled Trial].

Objective: To investigate the effect of esketamine on postoperative depression in frail elderly patients undergoing thoracoscopic radical resection of lung cancer.

Methods: A total of 88 frail elderly patients undergoing elective thoracoscopic radical resection of lung cancer were assigned randomly (using a randomization table) and in a double-blind way (blinding applies to both researchers and patients) to an esketamine group (Esk group, n = 44) and a normal saline group (NS group, n = 44). In the Esk group, 0.25 mg/kg esketamine was injected intravenously during anesthesia induction, followed by continuous infusion of esketamine at 0.125 mg/kg per hour until 20 min before the end of surgery. In the NS group, equivalent volumes of normal saline were administered using the same method. The primary outcome was the score for the 17-item Hamilton Rating Scale for Depression (HAMD-17) on days 7 and 30 after surgery. The secondary outcomes included sleep quality and cognitive function. Sleep quality was assessed using the numerical rating scale (NRS) on days 1, 3, and 7 after surgery and the Pittsburgh Sleep Quality Index (PSQI) on day 30 after surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) on days 1, 3, 7, and 30 after surgery. The other indicators included the levels of serum brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), S100β protein, and neuron specific enolase (NSE) at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after surgery, as well as perioperative data and postoperative safety outcomes.

Results: Three patients were excluded from the Esk group and the NS group, respectively, and eventually, 41 patients in each group were included in the statistical analysis. There were no statistically significant differences between the two groups in terms of age, sex, body mass index, American Society of Anesthesiologists (ASA) classification, comorbidities, educational attainment, and the scores for HAMD-17, PSQI, and MMSE 1 day before surgery (P > 0.05). Concerning the primary outcome, compared with those of the NS group, the HAMD-17 scores of patients in the Esk group were significantly lower at 7 days (median [P₂₅, P₇₅]) (7 [6, 8] vs. 7 [6, 12], P = 0.045) and 30 days (6 [6, 7] vs. 7 [6, 9], P = 0.020) after surgery. Concerning the secondary outcomes, compared with those of the NS group, the sleep NRS scores of patients in the Esk group were significantly lower at 1, 3, and 7 days after surgery (P < 0.01), and the MMSE scores were significantly higher (P < 0.05). Concerning the other indicators, compared with those of the NS group, the concentrations of serum BDNF and 5-HT in the Esk group were significantly higher (P < 0.05 or 0.01) at T1-T3, while the content of S100β was significantly lower (P < 0.01) at T1-T3; the levels of serum NSE were significantly lower at T1 and T2 (P < 0.01); the consumption of propofol, sufentanil, remifentanil, and sevoflurane during surgery in the Esk group was significantly reduced (P < 0.05 or 0.01); the incidence of postoperative nausea/vomiting and hyperalgesia was significantly lower (P < 0.01); the duration of postoperative mechanical ventilation, length-of-stay in postanesthesia care unit (PACU), and postoperative length-of-stay in the hospital were significantly shorter (P < 0.01).

Conclusion: Esketamine can improve the postoperative depressive state, sleep quality, and cognitive function in frail elderly patients undergoing thoracoscopic radical resection of lung cancer.