Objectives: 

Pao₂/Fio₂ is used commonly for diagnosis of lung injury (acute respiratory distress syndrome and transfusion-related acute lung injury), for assessment of pulmonary disease course and therapy, and in pulmonary transplantation for evaluation of donor lungs and clinical outcome. It was developed for convenience, without formal mathematical and graphic assessment to validate its suitability for these purposes.

Design: 

We examined, mathematically and graphically, the relationship of Pao₂/Fio₂ to Fio₂ at constant normal and several degrees of increased intrapulmonary shunting (Qs/Qt), assessing the impact of intra- and extrapulmonary factors on the relationship and thus the reliability of Pao₂/Fio₂.

Measurements and Main Results: 

The relationship of Pao₂/Fio₂ varies at all shunt fractions but most with Qs/Qt from 0.1 to 0.3 with Fio₂ approximately greater than 0.4. At higher Qs/Qt, the relationship is more constant and changes less with Fio₂ more than 0.4. Hemoglobin concentration and arterial-venous oxygen content difference have large effects that can confound interpretation of Pao₂/Fio₂. Barometric pressure has a substantial effect; Pco₂, base excess, and respiratory quotient have small effects.

Conclusions: 

At high Qs/Qt with Fio₂ more than 0.4, the relationship of Pao₂/Fio₂ to Fio₂ is relatively constant. However, with Qs/Qt of 0.1–0.3, Pao₂/Fio₂ changes substantially with Fio₂. Understanding the important effects of nonpulmonary factors (especially hemoglobin concentration and arterial-venous oxygen content difference) should enhance appropriate clinical use, interpretation of Pao₂/Fio₂, and interpretation of previous publications and future studies (especially those seeking to assess effects of anemia or transfusion on lung function). The ratio of Pao₂/Fio₂ is a good tool for some, but not many clinical circumstances, and is insufficiently robust for most research applications.