Benefits and risks of the P/F approach
The PaO2/FIO2 ratio represents the pressure exerted in the blood by the unbound molecules of oxygen, normalized to the fractional volume of inspired oxygen. The PaO2/FIO2 ratio is used to assess the lung’s capability to oxygenate the blood, primarily in ARDS, where its thresholds of 150, 200, and 300 are used/proposed to classify ARDS severity [1, 2]. Ideally, a given PaO2/FIO2 ratio value should correspond to a definite lung severity, independently of FIO2. In reality, the same severity may be associated with quite different PaO2/FIO2 values, depending on several factors, as previously described .
Consequently, an identical PaO2/FIO2 ratio of 150 measured at the barometric pressure of Mexico City (2250 m) or Göttingen (150 m) in two patients breathing 30% O2, with identical PaCO2/R ratios, would result in a sharply different PaO2/PAO2 ratios: 0.32 in Göttingen, decidedly less than the 0.49 in Mexico. The impact of PaCO2/R ratio on PAO2 is less dramatic, unless extracorporeal CO2 removal is in use. In this case, the R may be very low, producing a consistent decrease in the alveolar PO2, if FIO2 is not adequately increased [4, 5, 6].
CcO2 strictly depends on PAO2, which is proportional to the FIO2 (Eq. 1), while the CaO2 is proportional to the PaO2 (through the oxygen dissociation curve) . Therefore, the difference (CcO2 – CaO2) and the ratio (CaO2/CcO2) are strictly related and hold the same physiological meaning of PaO2/FIO2 ratio.
Because the (CcO2 – CaO2) difference equals the product: [venous admixture × (CcO2 – CvO2)], the same (CcO2 – CaO2), i.e., the same PaO2/FIO2, may derive from myriad combinations of venous admixture fraction and (CcO2 – CvO2). These range from extremely high venous admixture fraction and low (CcO2 – CvO2), i.e., high CvO2, or vice versa.
CcO2 primarily depends on FIO2; therefore, for a given FIO2 any change of (CcO2 – CvO2) only depends upon the CvO2.
CvO2, for a given arterial oxygenation, strictly depends on oxygen consumption (VO2) and cardiac output (Qt); indeed, CvO2 = CaO2 – VO2/Qt.
PaO2 is lower at higher venous admixture levels and increases non-linearly with FIO2 along the iso-venous admixture lines.
For a given oxygen consumption and venous admixture level, cardiac output exerts a tremendous effect on PaO2. It must be stressed, however, that the primary determinant is the CvO2 (see point 4 above).
Assessment of severity
Although the PaO2/FIO2 ratio has limits as a surrogate of venous admixture, the PaO2/FIO2 ratio offers several advantages: first, it is easy to measure; second, when tested across large populations (but not necessarily in individual patients), the PaO2/FIO2 reflects reasonably well the severity of anatomical derangements measured by CT scanning . Nonetheless, the accuracy of PaO2/FIO2 ratio for indexing ARDS severity (e.g., Berlin ARDS definition) would improve greatly if determined at a standard PEEP value. In previous work , we used 5 cmH2O to avoid the masking effect of higher PEEP on PaO2/FIO2 ratio, which may be due either to decreasing venous admixture or altering hemodynamics. Standardization of FIO2 would further improve the accuracy and comparability of severity among patients .
Changes in PaO2/FIO2 ratio are frequently used to assess recruitability during ARDS, on the assumption that increases in PaO2/FIO2 ratio are due to lung recruitment . Unfortunately, increasing PEEP often decreases cardiac output. Theoretically, if the venous admixture and oxygen consumption do not change, this would reduce the PaO2/FIO2 ratio. However, this seldom occurs, as the venous admixture usually changes in proportion to the cardiac output [12, 13, 14, 15]. Therefore, caution must be used when setting PEEP with the PaO2/FIO2 approach, as its apparent that improvement may be due to decreased cardiac output in the absence of recruitment—a principle long known but often forgotten.
PaO2/FIO2 ratio is a surrogate of venous admixture measurement for approximating ARDS severity and relates well to anatomical differences on the CT scan.
At a given venous admixture, the PaO2/FIO2 ratio may differ, depending on oxygen consumption and cardiac output. Conversely, for the same PaO2/FIO2, venous admixture may vary with FIO2.
To better assess severity of lung injury and follow its evolution, PaO2/FIO2 ratio should be measured at standardized levels of PEEP and FIO2. Selecting PEEP according to PaO2/FIO2 ratio may be misleading if hemodynamics are not taken into account.
Compliance with ethical standards
Conflicts of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
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