Key result
Angiotensin-II salvage therapy in patients with refractory shock did not significantly reduce norepinephrine equivalents by hour three (increase from 0.67 to 0.76 mcg/kg/min, p=0.326) and was associated with a 90% mortality rate prior to discharge.
Why the study?
Cost barriers have led to angiotensin-II being used later in shock progression as salvage therapy, which is inconsistent with how the drug was initially studied.
Does angiotensin-II reduce norepinephrine equivalents when used as salvage therapy in patients with refractory shock?
Observational (n=21)
No
Does angiotensin-II reduce norepinephrine equivalents when used as salvage therapy in patients with refractory shock?
p-value: p=0.326
Angiotensin-II used as a late salvage therapy in refractory shock does not significantly reduce vasopressor requirements and is associated with high mortality.
May not reduce vasopressor needs as late salvage in refractory shock; leaves open whether earlier use improves outcomes in prospective trials.
Background Angiotensin-II was approved for use in 2017 for the treatment of vasodilatory shock. Since then, significant cost barriers have led to its use later in the pathology of shock, which is inconsistent with how the drug was initially studied. Objectives The purpose was to investigate the effectiveness of angiotensin-II as salvage therapy in patients with refractory shock. The primary objective was reduction in norepinephrine equivalents after angiotensin-II initiation. Methods This retrospective, observational analysis includes all patients who received angiotensin-II from the time of initial formulary approval (January 2019) through the time of this analysis (January 2023). The primary endpoint was absolute change in norepinephrine equivalents from initiation of angiotensin-II (hour 0) to hour three. Secondary endpoints were percent change in norepinephrine equivalents from hour 0 to 3 and patient disposition at discharge. Wilcoxon signed rank test was performed for the primary and secondary outcomes utilizing SPSS software. Results Twenty-one patients were included. Fourteen (67%) presented with distributive shock. At angiotensin-II initiation, 76% of patients were on at least three other vasopressors at a norepinephrine equivalent rate of 0.67 mcg/kg/min. The primary outcome was a 13% increase in norepinephrine equivalents by hour three to 0.76 mcg/kg/min. Nineteen of the 21 patients (90%) died prior to discharge, with three of those patients not surviving to hour three. A subgroup analysis of only distributive shock patients resulted in a decrease in norepinephrine equivalents of 0.06 mcg/kg/min (p=0.374) by hour three. Conclusion Angiotensin-II is ineffective when utilized later in the progression of shock.
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Hawthorne et al. (2025) conducted an observational in Refractory shock (n=21). Angiotensin-II was evaluated on Absolute change in norepinephrine equivalents from initiation of angiotensin-II (hour 0) to hour three (p=0.326). Angiotensin-II salvage therapy in patients with refractory shock did not significantly reduce norepinephrine equivalents by hour three (increase from 0.67 to 0.76 mcg/kg/min, p=0.326) and was associated with a 90% mortality rate prior to discharge.
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