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

Background. The second gas effect (SGE) is considered to be significant only during periods of large volume N₂O uptake (VN₂ O); 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. Methods. 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. Results. Sevoflurane Fa/Fi was larger in the N₂O groups than in the O₂ groups, and it was identical in all four N₂O groups. Conclusions. 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.