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Title: Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock.
Austin Authors: Leisman, Daniel E;Handisides, Damian R;Chawla, Lakhmir S;Albertson, Timothy E;Busse, Laurence W;Boldt, David W;Deane, Adam M;Gong, Michelle N;Ham, Kealy R;Khanna, Ashish K;Ostermann, Marlies;McCurdy, Michael T;Thompson, B Taylor;Tumlin, James S;Adams, Christopher D;Hodges, Tony N;Bellomo, Rinaldo 
Affiliation: Department of Medicine, Massachusetts General Hospital, 55 Fruit St., GRB 7-730, Boston, MA, 02114, USA.;Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Innoviva Specialty Therapeutics, Waltham, MA, USA.
Department of Medicine, Veterans Affairs Medical Center, San Diego, CA, USA.
Departments of Medicine, Emergency Medicine and Anesthesiology, School of Medicine, UC Davis, Sacramento, CA, USA.
Department of Medicine, Emory University, Atlanta, GA, USA.;Emory Critical Care Center, Emory Healthcare, Atlanta, GA, USA.
Division of Critical Care, Department of Anesthesiology and Perioperative Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Medicine and Radiology, Royal Melbourne Hospital, The University of Melbourne, Melbourne Medical School, Parkville, Australia.
Division of Critical Care Medicine, Division of Pulmonary Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Critical Care, Mayo Clinic, Phoenix, AZ, USA.
Department of Anesthesiology, Section On Critical Care Medicine, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.;Perioperative Outcomes and Informatics Collaborative (POIC), Winston-Salem, NC, USA.;Outcomes Research Consortium, Cleveland, OH, USA.
Department of Critical Care, King's College London, Guy's & St Thomas' Hospital, London, UK.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.;Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Renal Division, Department of Medicine, Emory University Medical Center, Emory University, Atlanta, GA, USA.
Innoviva Specialty Therapeutics, Waltham, MA, USA.
Data Analytics Research and Evaluation (DARE) Centre
Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE), Melbourne, Australia.;Intensive Care Unit, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Intensive Care
Issue Date: 16-Dec-2023
Date: 2023
Publication information: Annals of Intensive Care 2023-12-16; 13(1)
Abstract: 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. 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. 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. 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. ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).
DOI: 10.1186/s13613-023-01227-5
ORCID: 0000-0001-9670-9425
Journal: Annals of Intensive Care
Start page: 128
PubMed URL: 38103056
Type: Journal Article
Subjects: ARDS
Angiotensin II
Renin–angiotensin system
Appears in Collections:Journal articles

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