Investigation of Esketamine Administration During Surgical Procedures for the Alleviation of Postoperative Anxiety and Depression in Adolescent Patients: A Randomized Controlled Trial.
Subanesthetic-dose esketamine given at skin incision significantly reduced postoperative anxiety scores on days 1, 3, 7, and 14, and reduced depression scores only on day 14, without significant differences in inflammatory markers or adverse events.
Abstract
Surgical stress can lead to postoperative anxiety and depression, especially in adolescents. These complications reduce quality of life and increase medical burdens, but perioperative psychological interventions for adolescents are limited, and related mechanisms remain unclear. Esketamine (S-ketamine), an N-methyl-D-aspartate receptor (NMDAR) antagonist, has analgesic, sedative, antidepressant, and anxiolytic effects, yet its efficacy and safety in adolescent surgical patients have not been systematically studied. This study seeks to investigate the prophylactic efficacy of subanesthetic-dose S-ketamine in mitigating postoperative anxiety and depression among adolescent patients. In this prospective double-blind randomized placebo-controlled trial, 92 American Society of Anesthesiologists (ASA) I-II adolescents aged 13-18 years undergoing elective surgery were randomly assigned to receive intravenous esketamine (0.25 mg/kg) or normal saline at skin incision. Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale (HADS); serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured; pain was evaluated using the NRS. Adverse events were recorded. Eighty patients completed the study. The esketamine group had significantly lower anxiety scores on postoperative days 1, 3, 7, and 14 (P < 0.05). Depression scores differed significantly only on day 14 (P = 0.043). There were no significant between‑group differences in inflammatory markers or adverse events. Esketamine was a protective factor against postoperative anxiety (OR = 0.38, P < 0.05). Subanesthetic-dose esketamine during surgery effectively reduces postoperative anxiety and partially alleviates depressive symptoms in adolescents with acceptable safety. Limited by sample size and single‑center design, multicenter studies with longer follow‑up are warranted.