Potential association between chronic alpha-1 adrenergic blockade and early epinephrine-related resuscitation profiles during cardiac arrest: a retrospective exploratory cohort study.

BACKGROUND AND OBJECTIVES: Epinephrine remains central to advanced cardiac life support through combined alpha- and beta-adrenergic effects. Alpha-mediated vasoconstriction increases aortic diastolic and coronary perfusion pressures, while beta-adrenergic, particularly beta-2, actions may contribute to pulse generation and ROSC. This study explored whether chronic alpha-1 blocker therapy is associated with early resuscitation profiles in epinephrine-treated cardiac arrest patients. MATERIALS AND METHODS: This retrospective cohort study included adults who received intravenous epinephrine during cardiac arrest between 2014 and 2025. The primary exploratory endpoint was operationally defined refractory arrest, based on cumulative epinephrine dose ≥3 mg and/or CPR duration ≥20 min without sustained ROSC, and was assessed separately from failure to achieve sustained ROSC. Baseline imbalance was evaluated using standardized mean differences. Because the exposed group was small, a prespecified parsimonious logistic regression model adjusted for age, sex, arrest location, and initial rhythm. RESULTS: Among 2,472 patients, 74 (3.0%) were receiving chronic alpha-1 blocker therapy; all included patients received epinephrine during CPR. Refractory arrest, distinct from ROSC failure, occurred in 45/74 (60.8%) alpha-blocker users versus 840/2,398 (35.0%) non-users (adjusted OR 3.06, 95% CI 1.88-4.97). Failure to achieve sustained ROSC occurred in 47/74 (63.5%) versus 1,002/2,398 (41.8%) patients (adjusted OR 2.64, 95% CI 1.62-4.31), while ROSC was lower among alpha-blocker users (adjusted OR 0.38, 95% CI 0.23-0.62). Early mortality occurred in 54/74 (73.0%) versus 636/2,398 (26.5%) patients (adjusted OR 7.15, 95% CI 4.20-12.15). Meaningful baseline imbalance was present, particularly for coronary artery disease and age (SMD 1.619 and 1.087, respectively). CONCLUSIONS: Chronic alpha-1 blocker therapy was associated with unfavorable early resuscitation outcomes among epinephrine-treated cardiac arrest patients. These exploratory findings do not establish causality and should be interpreted cautiously because of baseline imbalance, possible residual confounding, incomplete resuscitation-level covariates, and the small exposed group. Further multicenter studies with richer physiologic, pharmacologic, and statistical characterization are needed.