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Title: Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock.
Austin Authors: Bellomo, Rinaldo ;Wunderink, Richard G;Szerlip, Harold;English, Shane W;Busse, Laurence W;Deane, Adam M;Khanna, Ashish K;McCurdy, Michael T;Ostermann, Marlies;Young, Paul J;Handisides, Damian R;Chawla, Lakhmir S;Tidmarsh, George F;Albertson, Timothy E
Affiliation: Department of Medicine and Radiology, Royal Melbourne Hospital, The University of Melbourne, Melbourne Medical School, Parkville, Australia
Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
Department of Medicine (Critical Care), University of Ottawa, Ottawa, Ontario, Canada
School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
Outcomes Research Consortium, Cleveland, OH, USA
Department of Veterans Affairs, Northern California Health System, Mather, CA, USA
Division of Pulmonary & Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA
Department of Medicine, Division of Nephrology, Baylor University Medical Center, Dallas, TX, USA
Stanford University School of Medicine, Palo Alto, CA, USA
Department of Medicine, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
La Jolla Pharmaceutical Company, San Diego, CA, USA
Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
Centre for Integrated Critical Care, Department of Medicine & Radiology, The University of Melbourne, Melbourne, Australia
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, University of California, Davis, Sacramento, CA, USA
Medical Research Institute of New Zealand, Wellington, New Zealand
Department of Critical Care, King's College London, Guy's & St Thomas' Hospital, London, UK
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 2020 2020-02-06
Publication information: Critical Care 2020; 24(1): 43
Abstract: 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. 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. 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. 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. identifier NCT02338843. Registered 14 January 2015.
DOI: 10.1186/s13054-020-2733-x
ORCID: 0000-0002-1650-8939
PubMed URL: 32028998
Type: Journal Article
Subjects: ACE
ACE dysfunction
Angiotensin I
Angiotensin II
Vasodilatory shock
Appears in Collections:Journal articles

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