Hypoxemia frequently coexists with hypercapnic respiratory failure. When feasible, the alveolar-arterial gradient (PAO2 – PaO2 also known as the A-a gradient) should be calculated (from a room air blood gas) to distinguish hypercapnic respiratory failure due to global hypoventilation (extrapulmonary respiratory failure) from respiratory failure due to abnormal gas exchange from intrinsic lung disease. Since the range for a normal gradient increases with age, the gradient can be approximated by the equation A-a gradient = age x 0.3. An A-a gradient within the normal range in the setting of an elevated PaCO2 is highly suggestive of global hypoventilation, whereas a widened gradient >20 mmHg suggests that underlying lung disease may be contributing to the measured hypercapnia. Measuring the A-a gradient is more readily applied to patients in the chronic stable state and difficult to perform in patients with acute presentations because patients with acute hypercapnia often require the immediate application of supplemental oxygen, which precludes calculating a room air A-a gradient; however, if feasible, it is appropriate to draw an initial ABG prior to initiation of supplemental oxygen. An A-a gradient can also be reliably determined in situations where the fraction of inspired oxygen (FiO2) is accurate (eg, mechanical ventilation).
As an example, global hypoventilation from sedatives is likely the primary cause of hypercapnic respiratory acidosis in an otherwise healthy young drug abuser with somnolence, a normal chest radiograph, positive toxicology screen, and a normal A-a gradient of <20 mmHg. In contrast, abnormal gas exchange from increased dead space in patients with a COPD exacerbation or end stage interstitial lung disease (ILD) is typically associated with the usual clinical signs and symptoms of a COPD or ILD exacerbation and an ABG that reveals hypercapnia and a widened A-a gradient.