Early hemodynamic response to angiotensin II defines a prognostic phenotype in bloodstream infection–associated septic shock

BACKGROUND: Angiotensin II is increasingly used as an adjunctive vasopressor in septic shock, but the clinical significance and determinants of early hemodynamic response remain incompletely understood. METHODS: We performed a retrospective cohort study of adults with bloodstream infection-associated septic shock treated with angiotensin II between 2019 and 2025. Early hemodynamic response was quantified as the proportional reduction in background norepinephrine-equivalent dose (NED) 3 h after angiotensin II initiation and analyzed as a continuous variable. The primary outcome was 30-day mortality. Multivariable logistic regression and 3-h landmark Cox proportional hazards models were used to evaluate associations between response magnitude and mortality. RESULTS: A total of 320 patients met inclusion criteria, of whom 207 (64.7%) were male and the mean age was 63.7 years (SD 14.7). Greater proportional reductions in NED at 3 h were independently associated with lower 30-day mortality (adjusted OR per 10% reduction, 0.83; 95% CI 0.76-0.90; p < 0.001), with similar findings in 3-h landmark Cox modeling (adjusted HR per 10% reduction, 0.89; 95% CI 0.85-0.92; p < 0.001). Findings were consistent when response was modeled using absolute reductions in NED and when angiotensin II was incorporated into total vasopressor burden. CONCLUSIONS: Greater reductions in vasopressor requirements following angiotensin II initiation were strongly associated with improved survival in bloodstream infection-associated septic shock. This relationship was best characterized as a continuous physiologic gradient, with progressively larger reductions in norepinephrine-equivalent dose associated with lower mortality rather than a discrete threshold effect.