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P_aO₂/F_IO₂-Based Stratification Discriminates Treatment Failure in Nonintubated Subjects With ARDS

Masaaki Sakuraya^1,2, Kazuma Nagata³, Toshiki Yokoyama⁴

¹Dr. Sakuraya is affiliated with Department of Emergency and Intensive Care Medicine, JA Hiroshima General Hospital, Hatsukaichi, Japan.

Respiratory Care

|September 26, 2025

Abstract

Background:

The new global definition of nonintubated subjects with ARDS can be applied to patients receiving high-flow nasal cannula (HFNC), but stratification with P_aO₂/F_IO₂ has not been validated. We aimed to investigate the differences in oxygenation assessment between HFNC and CPAP for predicting outcomes.

Methods:

We performed a post hoc analysis of a multi-center randomized controlled trial conducted in Japan, focusing on oxygenation assessments in subjects receiving HFNC or CPAP. Subjects with P_aO₂/F_IO₂ < 300 on CPAP at 5 cm H₂O were assigned to receive either HFNC or CPAP. Subjects were stratified into mild (P_aO₂/F_IO₂ ≥ 200 but <300), moderate (P_aO₂/F_IO₂ ≥ 100 but < 200), or severe (P_aO₂/F_IO₂ < 100) hypoxemia categories based on oxygenation levels during CPAP at 5 cm H₂O. The primary outcome was treatment failure (intubation or in-hospital death). Discriminative performance for treatment failure was evaluated using the area under the receiver operating characteristic curve (AUROC) for each device.

Results:

Of the 85 subjects analyzed, 31, 48, and 6 were classified as having mild, moderate, and severe hypoxemia, respectively. Treatment failure occurred more frequently in subjects with moderate and severe hypoxemia than in those with mild hypoxemia (mild 1/31 [3.2%], moderate: 12/48 [25.0%], severe: 3/6 [50.0%], P = .004). Compared with 1 of 38 subjects (2.6%) treated with CPAP, 21 of 47 subjects (44.7%) with HFNC experienced worsened oxygenation even after 30 min of treatment (P < .001). Subjects with HFNC had a lower AUROC of P_aO₂/F_IO₂ for treatment failure (0.66, 95% CI 0.54-0.79) than those with CPAP (0.82, 95% CI 0.74-0.90, P = .041).

Conclusions:

P_aO₂/F_IO₂-based stratification may help predict treatment failure in patients with nonintubated subjects with ARDS. However, a thorough oxygenation assessment is necessary because of the variability introduced by different respiratory support devices. CPAP might be superior to HFNC when predicting treatment failure.

Keywords:

acute respiratory distress syndrome continuous positive airway pressure high-flow nasal cannula hypoxemic respiratory failure oxygenation severity

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