• Daniel E Leisman, Fiore Mastroianni, Grace Fisler, Sareen Shah, Zubair Hasan, Mangala Narasimhan, Matthew D Taylor, and Clifford S Deutschman.
• Department of Medicine, Massachusetts General Hospital, Boston, MA.
• Crit Care Explor. 2020 Oct 1; 2 (10): e0230.

ObjectivesTo assess the early physiologic response to angiotensin-II treatment in patients with coronavirus disease 2019-induced respiratory failure and distributive shock.DesignRetrospective consecutive-sample cohort study.SettingThree medical ICUs in New York during the coronavirus disease 2019 outbreak.PatientsAll patients were admitted to the ICU with respiratory failure and were receiving norepinephrine for distributive shock.InterventionsThe treatment groups were patients who received greater than or equal to 1 hour of angiotensin-II treatment. Time-zero was the time of angiotensin-II initiation. Controls were identified using a 2:1 hierarchical process that matched for 1) date and unit of admission; 2) specific organ support modalities; 3) age; 4) chronic lung, cardiovascular, and kidney disease; and 5) sex. Time-zero in the control group was 21 hours post vasopressor initiation, the mean duration of vasopressor therapy prior to angiotensin-II initiation in the treated group.Measurements And Main ResultsMain outcomes were trajectories of vasopressor requirements (in norepinephrine-equivalent dose) and mean arterial pressure. Additionally assessed trajectories were respiratory (Pao2/Fio2, Paco2), metabolic (pH, creatinine), and coagulation (d-dimer) dysfunction indices after time-zero. We also recorded adverse events and clinical outcomes. Trajectories were analyzed using mixed-effects models for immediate (first 6 hr), early (48 hr), and sustained (7 d) responses. Twenty-nine patients (n = 10 treated, n = 19 control) were identified. Despite matching, angiotensin-II-treated patients had markedly greater vasopressor requirements (mean: 0.489 vs 0.097 µg/kg/min), oxygenation impairment, and acidosis at time-zero. Nonetheless, angiotensin-II treatment was associated with an immediate and sustained reduction in norepinephrine-equivalent dose (6 hr model: β = -0.036 µg/kg/min/hr; 95% CI: -0.054 to -0.018 µg/kg/min/hr, p interaction=0.0002) (7 d model: β = -0.04 µg/kg/min/d, 95% CI: -0.05 to -0.03 µg/kg/min/d; p interaction = 0.0002). Compared with controls, angiotensin-II-treated patients had significantly faster improvement in mean arterial pressure, hypercapnia, acidosis, baseline-corrected creatinine, and d-dimer. Three thrombotic events occurred, all in control patients.ConclusionsAngiotensin-II treatment for coronavirus disease 2019-induced distributive shock was associated with rapid improvement in multiple physiologic indices. Angiotensin-II in coronavirus disease 2019-induced shock warrants further study.Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

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