Trajectory of PaO2/FiO(2) Ratio in Shock After Angiotensin II

Introduction High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO2/FiO(2) and SpO(2)/FiO(2) in patients in shock. Methods Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO2, SpO(2), and FiO(2) were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO2/FiO(2) and SpO(2)/FiO(2) were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO2/FiO(2) <= 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined. Results The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO2/FiO(2) change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p < .001; hourly SpO(2)/FiO(2) change -3.1/hr, 95% CI-3.7 to -2.4, p < .001). Ang-2 treatment was associated with significant improvements in PaO2/FiO(2) and SpO(2)/FiO(2) in the 48-h after initiation (hourly PaO2/FiO(2) change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p = .003; hourly SpO(2)/FiO(2) change +0.9/hr, 95% CI 0.5-1.2, p < .001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant (p(interaction) < 0.001 for both PaO2/FiO(2) and SpO(2)/FiO(2)). This improvement was associated with significantly fewer patients having a PaO2/FiO(2) <= 300 mm Hg at 48 h compared to baseline (mean difference -14.9%, 95% CI -25.3% to -4.6%, p = .011). Subgroup analysis found that patients with either a baseline PaO2/FiO(2) <= 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 mu g/kg/min had the greatest associations with oxygenation improvement. Conclusions Ang-2 is associated with improved PaO2/FiO(2) and SpO(2)/FiO(2). The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery.