Perioperative Ketamine Exposure and Postoperative Atrial Fibrillation/Flutter Risk After Video-Assisted Thoracoscopic Surgery: A Multi-Institutional Study
Kuo-Chuan Hung, Ting-Sian Yu, Yi-Chen Lai, Chia-Hung Yu, Jheng-Yan Wu, Wen-Wen Tsai, I-Wen Chen
Abstract
Purpose: To investigate the association between perioperative ketamine exposure and postoperative atrial fibrillation/flutter (POAF) risk following video-assisted thoracoscopic surgery (VATS). Patients and methods: A retrospective cohort study utilizing the TriNetX Research Network database analyzed adult patients aged ≥18 years who underwent elective VATS between January 2010 and April 2025. After excluding patients with pre-existing arrhythmias, critical illness, and emergency procedures, propensity score matching created 7,972 matched pairs comparing patients receiving perioperative ketamine/esketamine versus standard non-opioid analgesics (ketorolac/celecoxib). Primary outcome was 30-day POAF incidence. Secondary outcomes included other cardiac arrhythmias, pneumonia, mortality, and opioid use assessed at 30 days and 30-90 day intervals. Results: Ketamine exposure was significantly associated with an increased 30-day POAF risk (2.9% vs 2.2%; hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.10-1.62, p=0.004) and other cardiac arrhythmias (2.0% vs 1.3%; HR 1.60, 95% CI 1.25-2.06, p<0.001). Sensitivity analyses confirmed these findings, with POAF risk elevated in the medical center (HR 1.37, 95% CI 1.10-1.71), contemporary (HR 1.32, 95% CI 1.07-1.62), and non-malignant cohorts (HR 1.49, 95% CI 1.12-1.98). No significant interaction effects were observed in the subgroup analyses. Delayed mortality between 30-90 days was higher with ketamine (HR 1.54, 95% CI 1.07-2.20, p=0.018). Multivariable analysis confirmed ketamine as an independent predictor of POAF (HR 1.25, 95% CI 1.07-1.47, p=0.006). Conclusion: Our findings suggest a potential association between perioperative ketamine exposure and POAF; however, given the retrospective design and substantial unmeasured confounding, prospective studies with detailed anesthetic and opioid dosing information are required to clarify this relationship.