A Multicenter Observational Cohort Study of Angiotensin II in Shock

Abstract

Introduction: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population.

Methods: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy.

Results: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds.

Conclusion: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.

Keywords: angiotensin II; refractory shock; renin-angiotensin-aldosterone-system; sepsis; shock; vasopressor.

Figure 1.

Hemodynamic parameters at hour 0 and hour 3 of therapy. Shown are MAP (upper panel) and NEpi-equivalent dose (lower panel) at hours 0 and 3 of Ang-2 treatment. The mean differences in hemodynamic parameters were calculated with a 95% confidence interval (CI) and compared with a Wilcoxon signed-rank test. There was a significant improvement in MAP and NEpi-equivalent dose after the addition of angiotensin II, p < 0.001 for both outcomes. In the box plots, the horizontal line inside each box indicates the median, the top and bottom of the box indicate the interquartile range, the I bars indicate the 5th and 95th percentiles, and the circles indicate outliers. The dashed line indicates a MAP of 65 mmHg. Abbreviations: MAP = mean arterial pressure, NEpi = norepinephrine, mmHg = millimeters of mercury, mcg = micrograms, NEpi = norepinephrine, ng = nanograms, mL = milliliters, hr = hour.