End-tidal to Arterial Gradients and Alveolar Deadspace for Anesthetic Agents

Background: According to the "three-compartment" model of ventilation-perfusion ((V) over dot(A)/(Q) over dot) inequality, increased (V) over dot(A)/(Q) over dot scatter in the lung under general anesthesia is reflectedin increased alveolar deadspace fraction (VDA/VA) customarily measured using end-tidal to arterial (A-a) partial pressure gradients for carbon dioxide. A-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment VDA/VA calculated using partial pressures of four inhalational agents (VDA/VAG) is different from that calculated using carbon dioxide (VDA/VACO(2)) measurements, but similar to predictions from multicompartment models of physiologically realistic "log-normal" (V) over dot(A)/(Q) over dot distributions. Methods: In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. VDA/VA was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (PAG) and end-capillary partial pressure (PC'G) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. Results: Calculated VDA/VAG was larger (mean +/- SD) for halothane ( 0.47 +/- 0.08), isoflurane ( 0.55 +/- 0.09), sevoflurane (0.61 +/- 0.10), and desflurane (0.65 +/- 0.07) than VDA/VACO(2) (0.23 +/- 0.07 overall), increasing with lower blood solubility ( slope [Cis], -0.096 [-0.133 to - 0.059], P < 0.001). There was a significant difference between calculated ideal PAG and PC'G median [interquartile range], Pag 5.1 [3.7, 8.9] versus PC'G 4.0 [ 2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated VDA/VAG. Conclusions: Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment (V) over dot(A)/(Q) over dot scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace.