Physiologic Response to Angiotensin II Treatment for Coronavirus Disease 2019-Induced Vasodilatory Shock: A Retrospective Matched Cohort Study

Objectives: To assess the early physiologic response to angiotensin-II treatment in patients with coronavirus disease 2019-induced respiratory failure and distributive shock. Design: Retrospective consecutive-sample cohort study. Setting: Three medical ICUs in New York during the coronavirus disease 2019 outbreak. Patients: All patients were admitted to the ICU with respiratory failure and were receiving norepinephrine for distributive shock. Interventions: The 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 Results: Main 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, pinteraction=0.0002) (7 d model: β = -0.04 µg/kg/min/d, 95% CI: -0.05 to -0.03 µg/kg/min/d; pinteraction = 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. Conclusions: Angiotensin-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.