Trajectory of PaO₂/FiO₂ 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/FiO₂ and SpO₂/FiO₂ 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, SpO₂, and FiO₂ were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO₂/FiO₂ and SpO₂/FiO₂ were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO₂/FiO₂ ≤ 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/FiO₂ change −4.7 mm Hg/hr, 95% CI − 6.0 to −3.5, p <.001; hourly SpO₂/FiO₂ change −3.1/hr, 95% CI−3.7 to −2.4, p <.001). Ang-2 treatment was associated with significant improvements in PaO₂/FiO₂ and SpO₂/FiO₂ in the 48-h after initiation (hourly PaO₂/FiO₂ change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p =.003; hourly SpO₂/FiO₂ 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/FiO₂ and SpO₂/FiO₂). This improvement was associated with significantly fewer patients having a PaO₂/FiO₂ ≤ 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/FiO₂ ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement. Conclusions: Ang-2 is associated with improved PaO₂/FiO₂ and SpO₂/FiO₂. 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.