Accurately assessing and managing oxygenation disturbances is critical to optimal patient outcomes. The alveolar to arterial (A-a) oxygen gradient, which is the difference between the amount of the oxygen in the alveoli (the alveolar oxygen tension [PAO
2]) and the amount of oxygen dissolved in the plasma (PaO
2), is an important measure to help narrow the cause of hypoxemia. It describes the overall efficiency of oxygen uptake from alveolar gas to pulmonary capillary blood.
The Calculations
The basic formula is:
A-a oxygen gradient = PAO2 - PaO2
PaO
2 is measured by arterial blood gas, while PAO
2 is calculated using the alveolar gas equation:
PAO2 = (FiO2 x [Patm - PH2O]) - (PaCO2 ÷ R)
In this equation, FiO
2 is the fraction of inspired oxygen (0.21 at room air), Patm is the atmospheric pressure (760 mm Hg at sea level), PH
2O is the partial pressure of water (47 mmHg at 37⁰C), PaCO
2 is the arterial carbon dioxide tension, and R is the respiratory quotient (approximately 0.8 at steady state, but varies according to the relative utilization of carbohydrate, protein, and fat.)
In addition, the A-a gradient varies with age and can be estimated from the following equation:
A-a gradient = 2.5 + FiO2 x age in years
Important Notes
- In healthy patients, there is generally a small difference between PAO2 and PaO2 because PAO2 is approximately 100 mm Hg and PaO2 is about 95 mm Hg.
- Proper determination of the A-a gradient requires exact measurement of FiO2, most easily done when a patient is breathing room air or receiving mechanical ventilation. The FiO2 of patients receiving supplemental oxygen by nasal cannula or mask can be estimated, but this does limit the usefulness of the A-a gradient.
- The A-a gradient increases with higher FiO2. When a patient receives a high FiO2, both PAO2 and PaO2 increase. However, the PAO2 increases disproportionately, causing the A-a gradient to increase.
Clinical Implications
Measuring the A-a gradient helps narrow the cause of hypoxemia as either extrapulmonary (outside of the lungs) or intrapulmonary (inside of the lungs); in other words, to distinguish hypercapnic respiratory failure due to global hypoventilation (extrapulmonary respiratory failure) from respiratory failure due to abnormal gas exchange from intrinsic lung disease. An A-a gradient within the normal range (< 20 mm Hg) in the setting of an elevated PaCO
2 is highly suggestive of global hypoventilation, whereas a widened gradient (> 20 mm Hg) suggests that underlying lung disease may be contributing to the measured hypercapnia.
Let’s consider two patients…
Case #1
A young, healthy patient comes in with drug overdose and his respiratory rate is 8. His arterial blood gas (abg) on room air reveals a respiratory acidosis with hypoxemia 7.31/55/65/24/88%. Assuming the Patm
, PH
2O, and R are constant, we calculate his A-a gradient:
A-a oxygen gradient = [(FiO2 x [Patm - PH2O]) - (PaCO2 ÷ R)] - PaO2
A-a gradient = [(0.21) x (760-47) – (55 ÷ 0.8)] – 65
A-a gradient = [(149.73) – (68.75)] – 65
A-a gradient = 80.98 – 65
A-a gradient = 15.98
Since his A-a gradient is < 20 mm Hg, we conclude that his hypoxemia is caused by hypoventilation due to his central nervous system depression; his alveolar oxygenation and arterial oxygenation are both decreased, so the gradient between the two remains within normal limits. Use of the appropriate reversal agent is indicated to arouse him and stimulate his respirations; intubation and mechanical ventilation is indicated if reversal is not possible or is ineffective.
Case #2
A patient with pneumonia who is mechanically ventilated, is developing worsening hypoxemia. His FiO2 on the ventilator is increased to 80% and his abg also reveals a respiratory acidosis with hypoxemia: 7.31/55/65/24/88%. Again, assuming the Patm, PH2O, and R are constant, we calculate his A-a gradient:
A-a oxygen gradient = [(FiO2 x [Patm - PH2O]) - (PaCO2 ÷ R)] - PaO2
A-a gradient = [(0.80) x (760-47) – (55 ÷ 0.8)] – 65
A-a gradient = [(570.4) – (68.75)] – 65
A-a gradient = 501.65 – 65
A-a gradient = 436.65
In this patient, the increased A-a gradient (> 20 mm Hg) is due to his pneumonia creating a physical barrier within alveoli, limiting the transfer of oxygen into the capillaries. His alveolar oxygenation is normal, however his arterial oxygenation is decreased, so the gradient between the two is widened. This is an example of an intrapulmonary cause of hypoxemia. For this patient, treatment of his pneumonia will be critical to improving arterial oxygenation, while supportive pulmonary hygiene measures are provided.
It’s good to be familiar with this measurement and to feel comfortable recognizing what a normal or elevated A-a gradient indicate. Also, there are
tools and calculators for calculating the A-a gradient to help!
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