Hemodynamic Response to Low vs High Dose Angiotensin II in Patients With Septic Shock

Introduction: Angiotensin II (ATII) is used as an adjunctive vasopressor for septic shock, but the optimal dosing strategy remains uncertain. While higher infusion rates are permitted by regulatory labeling, evidence supporting benefit beyond moderate doses is limited. We hypothesized that titrating ATII to a lower maximum dose would yield comparable hemodynamic efficacy to higher dosing, with fewer adverse events.


Methods: We conducted a single-center, retrospective cohort study of adult patients with septic shock admitted to a medical ICU and initiated on ATII between March 2020 and February 2022. Patients were stratified by maximum ATII dose received: low-dose (≤20 ng/kg/min) vs. high-dose (>20–80 ng/kg/min). The primary outcome was hemodynamic response at 3 hours post-ATII initiation, defined as achieving a mean arterial pressure (MAP) ≥65 mmHg with a reduction in background vasopressor requirement. Secondary outcomes included change in MAP and norepinephrine-equivalents (NEE) from baseline to 3 hours, in-hospital mortality, safety events, and estimated drug costs. Descriptive statistics were used for outcome comparison.


Results: A total of 174 patients were included (low-dose n=101; high-dose n=73), and baseline characteristics were similar. Hemodynamic response at 3 hours occurred in 21% of the low-dose group and 22% of the high-dose group (p=0.179). There were no significant differences in change in MAP or NEE at 3 hours. In-hospital mortality exceeded 95% in both groups. New-onset cardiac arrhythmias were significantly more frequent in the high-dose group (11.5% vs. 23.8%; p=0.043), while thrombotic event rates were similar. Estimated per-patient ATII cost was approximately double in the high-dose group ($1,785 vs. $3,570).


Conclusions: Low- and high-dose ATII strategies resulted in comparable short-term hemodynamic outcomes in septic shock. However, higher doses were associated with increased arrhythmias and greater costs without evidence of added clinical benefit. These findings suggest that moderate ATII dosing (≤20 ng/kg/min) may optimize efficacy, safety, and resource utilization, though prospective studies are warranted.