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The major function of the lung is to exchange physiologic (respiratory) gases, namely oxygen (O2) and carbon dioxide (CO2). Once the lungs fail as a gas exchanger, arterial hypoxemia, hypercapnia, or both appear and respiratory failure ensues. Arterial PO2 (PaO2) and

image (
image) are the measurable end-point variables used routinely by clinicians to manage patients with acute respiratory failure. When the latter is severe, mechanical ventilation is then considered the final strategy for treating patients.

Classically, the mechanisms of hypoxemia are alveolar hypoventilation, limitation of alveolar to end-capillary O2 diffusion, intrapulmonary shunt, and ventilation–perfusion (

image) imbalance; the major causes of hypercapnia are alveolar hypoventilation and
image mismatching.1 Ideally, it would be of great interest to solely manage respiratory blood-gas measurements, such as alveolar-arterial PO2 difference P(A-a)O2, venous admixture ratio (
image), and physiologic dead space (dead-space-to-tidal-volume ratio [VD/VT]), as a general marker of the overall function of the lung. Thus, impaired or improved results of these variables, whose principal merits are their simplicity and relative ease of measurement, could reflect impaired or improved pulmonary gas exchange. Unfortunately, all these variables reflect not only the state of the lung, but also the conditions under which the lung is operating. These conditions, which uniquely determine the PO2 and
image in any single gas-exchange unit of the lung, are the
image ratio, the composition of inspired gas, and the composition of mixed venous blood heavily modulated by the behavior of the cardiac output.2,3 It is important to appreciate the key role played by these three factors governing the respiratory gases in any single gas-exchange unit.3

This chapter reviews the effect of ventilator support on pulmonary gas exchange using the multiple inert gas elimination technique (MIGET), an approach that represents a major conceptual breakthrough in our understanding of pulmonary medicine pathophysiology in disease states.47 MIGET has three major advantages. First, it estimates the pattern of pulmonary blood flow and alveolar ventilation and calculates the mismatch of

image relationships. Second, it partitions the P(A-a)O2 into determinants of intrapulmonary shunt,
image inequality, and diffusion limitation to O2. Third, it apportions and unravels arterial oxygenation into intrapulmonary, namely the latter three factors, and extrapulmonary components, that is, inspired PO2, overall ventilation, cardiac output, and O2 consumption. Of paramount importance is the ability to perform measurements at any fractional inspired oxygen concentration (FIO2) without perturbing the vascular and bronchomotor tones.8

Figure 37-1 illustrates the

image distribution obtained with MIGET in a healthy, young individual at rest breathing ambient air. Each data point represents a particular amount of blood flow or alveolar ventilation. Both overall pulmonary perfusion and total ventilation correspond to the sum of the respective data points (the lines have been drawn for clarity only). These quantities (distributions) are plotted ...

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