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

BACKGROUND According to the "three-compartment" model of ventilation-perfusion (VA/Q) inequality, increased VA/Q 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" VA/Q 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 VA/Q scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: General anesthesia increases the inhomogeneity (scatter) of the distribution of ventilation-perfusion ratios in the lung, widening alveolar to arterial partial pressure gradients for respired gasesThis inhomogeneity is reflected in increased alveolar deadspace fraction in the traditional three-compartment model of ventilation-perfusion scatterThe alveolar to arterial partial pressure difference for isoflurane is inconsistent with that measured simultaneously using end-tidal and arterial carbon dioxide partial pressures WHAT THIS ARTICLE TELLS US THAT IS NEW: Alveolar deadspace fraction calculated for volatile anesthetic agents is much larger than that calculated simultaneously for carbon dioxide, and its magnitude increases as blood solubility decreasesPhysiologically realistic multicompartment modeling of ventilation-perfusion scatter explains the relative differences between inhalational agents in alveolar to arterial partial pressure gradients and alveolar deadspace.