Perioperative Dexmedetomidine Exposure and One-Year Mortality Risk After Video-Assisted Thoracoscopic Surgery: A Multi-Institutional Study.

Purpose: To evaluate the association between perioperative dexmedetomidine exposure and one-year mortality risk following video-assisted thoracoscopic surgery (VATS). Patients and Methods: We conducted a multi-institutional retrospective cohort study using the TriNetX Research Network. Adult patients aged ≥18 years who underwent elective VATS between January 2010 and December 2024 were included in the study. Patients were categorized into dexmedetomidine or midazolam (control) groups based on perioperative medication exposure. Midazolam was selected as the active comparator as it represents a standard perioperative sedative with different pharmacological properties than dexmedetomidine. After applying the exclusion criteria, 1:1 propensity score matching was performed using demographic variables, comorbidities, and laboratory parameters. The primary outcome was all-cause mortality within one year; and the secondary outcome was overall major complications (composite of sepsis, acute respiratory failure, acute myocardial infarction, cerebral infarction, and acute kidney failure). Results: After propensity matching, 6387 patients were included in each group with balanced baseline characteristics. Patients receiving dexmedetomidine had significantly lower one-year mortality compared to midazolam (4.1% vs 5.4%; hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.68-0.94; p=0.007). This mortality difference was observed during the later follow-up period (31-365 days: HR:0.80; p=0.008) rather than the early postoperative period (1-30 days: HR:0.89; p=0.695). No difference was observed in overall major complications between groups (12.7% each; HR 1.05; p=0.289). Sensitivity and subgroup analyses confirmed these findings. Conclusion: Perioperative dexmedetomidine administration is associated with reduced one-year mortality following VATS compared to midazolam. The mortality benefit appears during the later follow-up period without differences in major complication rates. Future prospective randomized trials are needed to confirm these findings and determine optimal dosing strategies.