BackgroundSepsis and septic shock impose severe cardiovascular stress characterized by sympathetic overactivation and detrimental tachycardia, which is strongly linked to poor outcomes. While ultra-short-acting β1-blockers have shown promise in controlled trials for heart rate (HR) control, a critical gap remains regarding the optimal β1-selective regimen for complex, multimorbid, vasopressor-dependent patients with septic shock complicated by tachyarrhythmia in real-world settings.ObjectiveTo compare survival and hemodynamic trajectories associated with two intravenous β1-selective blockers—esmolol and metoprolol, when initiated during septic shock complicated by tachyarrhythmia in a real-world setting.MethodsIn this retrospective cohort study, we examined the MIMIC-IV database for vasopressor-dependent patients with septic shock and incident tachyarrhythmia. Employing propensity score matching and restricted cubic splines analysis, we compared the mortality of intravenous esmolol and metoprolol in septic shock patients with tachyarrhythmia.ResultsThe primary outcome was 28-day ICU mortality; the secondary outcomes were longitudinal hemodynamic indices (heart rate, blood pressure, lactate). Overall, 31.82% (1,494/4,695) cases died by day 28. Metoprolol was used in 44.6% and esmolol in 1.9%. In multivariable Cox models with spline-informed covariate handling, both esmolol and metoprolol were associated with lower 28-day mortality versus no β1-blocker (esmolol HR, 0.69; 95% CI, 0.51–0.95; metoprolol HR, 0.28; 95% CI, 0.25–0.32). Results remained directionally consistent after the concurrent exclusion of sinus tachycardia and ventricular fibrillation and in propensity-score–matched comparisons. Longitudinal analyses showed that survivors across all regimens maintained relatively stable SBP/DBP through day 8, whereas esmolol non-survivors exhibited marked SBP/DBP fluctuations with a concurrent lactate surge around day 2; metoprolol was associated with more stable trajectories.ConclusionIn real-world septic shock with arrhythmia, intravenous β1-blockade was associated with a more favorable 28-day survival trajectory, with metoprolol showing a more prominent survival association and more stable blood-pressure/lactate dynamics compared to esmolol.