Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock

• Type of Material: Article
• Authors: Daniel E. Leisman, Massachusetts General Hospital; Damian R. Handisides, Innoviva Specialty Therapeutics; Lakhmir S. Chawla, Veterans Affairs Medical Center, San Diego; Timothy E. Albertson, University of California, Davis; Laurence W. Busse, Emory University; David W. Boldt, University of California, Los Angeles; Adam M. Deane, University of Melbourne; Michelle N. Gong, Albert Einstein College of Medicine; Kealy R. Ham, Mayo Clinic, Phoenix; Ashish K. Khanna, Wake Forest University; Marlies Ostermann, King's College London; Michael T. McCurdy, University of Maryland, Baltimore; B. Taylor Thompson, Harvard University; James Tumlin, Emory University; Christopher D. Adams, Innoviva Specialty Therapeutics; Tony N. Hodges, Innoviva Specialty Therapeutics; Rinaldo Bellomo, Monash University
• Language: English
• Date: 2023-12-16
• Publisher: Springer
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1186/s13613-023-01227-5
• Title of Journal or Parent Work: Annals of Intensive Care
• Volume: 13
• Start Page: 128
• Grant/Funding Information: Data and statistical analysis support for this study was provided by Innoviva Specialty Therapeutics (Waltham, MA, USA).
• Keywords: Renin–angiotensin system; Shock; ARDS; Norepinephrine; Septic; Angiotensin II
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, General; Health Sciences, Pharmacology

Abstract

Background The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock.