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- Title
Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock.
- 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
- 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. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).
- Subjects
VASOCONSTRICTORS; STATISTICS; CONFIDENCE intervals; CATECHOLAMINES; RENIN-angiotensin system; ADULT respiratory distress syndrome; TREATMENT effectiveness; PLACEBOS; T-test (Statistics); RANDOMIZED controlled trials; DESCRIPTIVE statistics; RESEARCH funding; REACTIVE oxygen species; DATA analysis; HEMODYNAMICS; STATISTICAL sampling; ANGIOTENSIN II; OXYGEN in the body
- Publication
Annals of Intensive Care, 2023, Vol 13, Issue 1, p1
- ISSN
2110-5820
- Publication type
Article
- DOI
10.1186/s13613-023-01227-5