Large volume N2O uptake alone does not explain the second gas effect of N2O on sevoflurane during constant inspired ventilation

The second gas effect (SGE) is considered to be significant only during periods of large volume N2O uptake (VN2O); however, the SGE of small VN2O has not been studied. We hypothesized that the SGE of N2O on sevoflurane would become less pronounced when sevoflurane administration is started 60 min after the start of N2O administration when VN2O has decreased to ∼125 ml min−1, and that the kinetics of sevoflurane under these circumstances would become indistinguishable from those when sevoflurane is administered in O2. Seventy-two physical status ASA I–II patients were randomly assigned to one of six groups (n=12 each). In the first four groups, sevoflurane (1.8% vaporizer setting) administration was started 0, 2, 5 and 60 min after starting 2 litre min−1 O2 and 4 litre min−1 N2O, respectively. In the last two groups, sevoflurane (1.8 or 3.6% vaporizer setting) was administered in 6 litre min−1 O2. The ratios of the alveolar fraction of sevoflurane (Fa) over the inspired fraction (Fi), or Fa/Fi, were compared between the groups. Sevoflurane Fa/Fi was larger in the N2O groups than in the O2 groups, and it was identical in all four N2O groups. We confirmed the existence of a SGE of N2O. Surprisingly, when using an Fa of 65% N2O, the magnitude of the SGE was the same with large or small VN2O. The classical model and the graphical representation of the SGE alone should not be used to explain the magnitude of the SGE. We speculate that changes in ventilation/perfusion inhomogeneity in the lungs during general anaesthesia result in a SGE at levels of VN2O previously considered by most to be too small to exert a SGE.