Elucidating the roles of solubility and ventilation-perfusion mismatch in the second gas effect using a two-step model of gas exchange

The second gas effect occurs when high inspired concentrations of a first gas, usually nitrous oxide, enhance the uptake of other gases administered simultaneously. The second gas effect is greater in blood than in the gas phase, persists well into the period of nitrous oxide maintenance anesthesia, increases as the degree of ventilation-perfusion mismatch increases, and is most pronounced with the low soluble agents in current use. Yet, how low gas solubility and increased ventilation-perfusion mismatch can combine to improve gas transfer remains unclear, which is the focus of the present study. Specifically, we have used a two-step model of gas exchange to separate the effect of gas volume contraction, which accompanies the first gas uptake, from other factors. Step 1 involves the uptake of the second gas at constant volume. Contraction of gas volume takes place in step 2 and is most effective in transferring further amounts of gas to blood if the volume of second gas exposed to the contraction is maximized, i.e., if the loss of second gas in step 1 is minimized. Minimization depends on having a gas with a low solubility in blood and increases as the degree of ventilation-perfusion mismatch increases. The effectiveness of the contraction also requires a favorable alignment with the retained second gas. Alignment depends on the solubility of both gases and the degree of ventilation-perfusion mismatch. The model is fully consistent with classical concepts of gas exchange. NEW & NOTEWORTHY Gas exchange in the lung can always be represented as the sum of two components: gas exchange at constant volume followed by gas exchange on volume correction. Using this sequence to study the second gas effect, low gas solubility and increased ventilation-perfusion mismatch are shown to act together to enhance second gas uptake. While appearing to contravene classical concepts of gas exchange, a detailed theoretical analysis shows it is fully consistent with these concepts.