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Critical Care
Published in: Critical Care 1/2020

01-12-2020 | Shock | Research

Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock

Authors: Rinaldo Bellomo, Richard G. Wunderink, Harold Szerlip, Shane W. English, Laurence W. Busse, Adam M. Deane, Ashish K. Khanna, Michael T. McCurdy, Marlies Ostermann, Paul J. Young, Damian R. Handisides, Lakhmir S. Chawla, George F. Tidmarsh, Timothy E. Albertson

Published in: Critical Care | Issue 1/2020

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Abstract

Background

In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study.

Methods

We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes.

Results

Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30–676.00 pg/mL] vs 42 pg/mL [IQR 30.46–87.34 pg/mL] in controls; P <  0.0001) and median ANG I/II ratio (1.63 [IQR 0.98–5.25] vs 0.4 [IQR 0.28–0.64] in controls; P <  0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85–299.50 pg/mL] vs 97 pg/mL [IQR 35.27–181.01 pg/mL] in controls; P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P <  0.0001), lower ANG II levels (P <  0.0001), higher albumin concentrations (P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P <  0.00001), and they received a higher norepinephrine-equivalent dose (P = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36–0.88; P = 0.01) on unadjusted analyses.

Conclusions

Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction.

Trial registration

ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.
Appendix
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Metadata
Title
Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock
Authors
Rinaldo Bellomo
Richard G. Wunderink
Harold Szerlip
Shane W. English
Laurence W. Busse
Adam M. Deane
Ashish K. Khanna
Michael T. McCurdy
Marlies Ostermann
Paul J. Young
Damian R. Handisides
Lakhmir S. Chawla
George F. Tidmarsh
Timothy E. Albertson
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-2733-x

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