Effects of Intraoperative Esketamine–Dexmedetomidine Combination on Postpartum Depressive Symptoms and Neuropsychiatric Events Following Cesarean Delivery: A Randomized Controlled Trial

Purpose: This trial aims to compare the effects of intraoperative low-dose dexmedetomidine combined with esketamine versus esketamine alone on postpartum depressive and esketamine-related neuropsychiatric adverse events in cesarean delivery. Patients and Methods: In this randomized controlled trial, 134 parturients scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled. Following umbilical cord clamping, patients were randomly allocated to receive either 0.25 mg/kg esketamine combined with 0.5 μg/kg dexmedetomidine (Group DE, n=67) or 0.25 mg/kg esketamine alone (Group E, n=67). The study assessed Edinburgh Postnatal Depression Scale (EPDS) scores on postpartum days 7 and 42, the incidence of esketamine-related neuropsychiatric adverse events, maternal satisfaction, postoperative pain scores, and other adverse events. Results: On postpartum day 7, the Group DE exhibited significantly lower EPDS scores than the Group E (median [IQR]: 3.00 [2.00-4.00] vs 4.00 [3.00-5.00]; P < 0.001). This between-group difference was no longer significant at the 42-day follow-up. The overall incidence of neuropsychiatric adverse events was significantly reduced in the Group DE [22 (32.84%) vs 39 (58.21%), P =0.003], with notably fewer cases of dizziness (19.40% vs 35.82%, P =0.034) and headache (8.96% vs 23.88%, P =0.020). Additionally, the Group DE had lower rates of nausea (8.96% vs 23.88%, P =0.020) and tachycardia (20.90% vs 47.76%, P =0.001), and higher maternal satisfaction scores [10.00 (9.00-10.00) vs 9.00 (9.00-10.00), P =0.005]. Conclusion: Combined low-dose dexmedetomidine and esketamine during cesarean section provides a short-term improvement in early postpartum depressive symptoms, reduces intraoperative neuropsychiatric adverse events, and enhances maternal satisfaction, with a favorable maternal and neonatal safety profile.