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

Background: According to the "three-compartment"model of ventilation-perfusion () inequality, increased scatter in the lung under general anesthesia is reflected in 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/Vaco2) measurements, but similar to predictions from multicompartment models of physiologically realistic "log-normal"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/Vaco2 (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 scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace.