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.

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.


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.


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.

Editor’s Perspective
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 gases
  • This inhomogeneity is reflected in increased alveolar deadspace fraction in the traditional three-compartment model of ventilation-perfusion scatter
  • The 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 decreases
  • Physiologically realistic multicompartment modeling of ventilation-perfusion scatter explains the relative differences between inhalational agents in alveolar to arterial partial pressure gradients and alveolar deadspace