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.