Effect of esketamine-assisted regional block on post-traumatic stress disorder after radical lung cancer surgery: A retrospective clinical study

Background: Post-traumatic stress disorder (PTSD) is a common psychological complication after radical lung cancer surgery and has a significant impact on postoperative recovery and quality of life. Esketamine, a new anesthetic agent, may be protective against postoperative PTSD through modulation of neurotransmitter systems and anti-inflammatory actions.

Aim: To explore the underlying mechanisms by which esketamine-assisted regional block prevents postoperative PTSD in patients undergoing radical lung cancer surgery.

Methods: We conducted a retrospective review of the clinical data of 218 radical lung cancer surgery patients in our thoracic surgery department from January 2021 to December 2024. Patients were stratified by anesthetic protocol into a control group (regional block only, n = 106) and an esketamine group (esketamine assisted regional block, n = 112). At 3 months after the operation, postoperative PTSD occurrence was assessed by using the PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Preoperative and 24-hour postoperative serum levels of cortisol and interleukin (IL)-6 were examined by enzyme-linked immunosorbent assay. Logistic regression analysis was performed to identify risk factors and receiver operating characteristic curves were used to assess predictive efficacy.

Results: Among 218 enrolled patients (mean age: 58.4 ± 9.2 years; male proportion, 61.5%), there were 62 patients (28.4%) who developed PTSD at the postoperative period of 3 months. Esketamine injection was associated with considerably reduced PTSD rates relative to control (19.6% vs 37.7%, P < 0.001), a reduction of risk by 48% relative and an absolute risk difference of 18.1%. At 24 hours postoperatively, serum cortisol (326.4 ± 68.2 nmol/L vs 458.3 ± 92.6 nmol/L) and IL-6 levels (42.8 ± 12.6 pg/mL vs 68.4 ± 18.2 pg/mL) were significantly lower in the esketamine group compared with control subjects, respectively (P < 0.05). The multivariate analysis demonstrated that the esketamine use [odds ratio (OR) = 0.38; 95%CI: 0.19-0.74; P = 0.005], postoperative pain score (OR = 2.86; 95%CI: 1.52-5.38; P = 0.001) and postoperative IL-6 level (OR = 2.24; 95%CI: 1.18-4.26; P = 0.014) were independent factors contributing to PTSD occurrence. The combined prediction model had an area under the curve of 0.856 (95%CI: 0.802-0.910), and its sensitivity and specificity were respectively observed to be 78.7% and 84.6%.

Conclusion: Esketamine-assisted regional block could substantially reduce post-surgical PTSD prevalence after radical lung cancer surgery, probably via anti-stress-inflammation modulation. Post-operative pain management and inflammatory marker monitoring contribute to the better early diagnosis of potential high-risk PTSD patients. This study offers a new therapeutic strategy and theoretical foundation for the postoperative prevention of PTSD in lung cancer patients.