The second gas effect is not a valid concept

To determine whether the second gas effect is valid, we determined the pharmacokinetics of 0.2% enflurane with or without 80% N 2 O (n = 7 each) under controlled constant volume ventilation in 14 young healthy male patients before their operations. The alveolar (end-tidal) concentration (F A ) and inspired concentration (F I ) at the mouthpiece and the arterial blood concentration of enflurane were measured, and the ratio of F A to F I was calculated. The F A /F I of enflurane increased rapidly during the first few minutes of administration and then increased slowly. No significant difference was found in the F A /F I between the two groups at any time point (P > 0.05). The arterial blood concentrations of enflurane increased progressively and were not significantly different between the two groups at any time point (P > 0.05). The results indicate that, at high concentrations, N 2 O neither facilitated the increase of F A nor enhanced the uptake of a companion gas. The second gas effect is a nonexistent phenomenon in clinical practice because the concentrating effect is very weak and the augmentation effect is nonexistent under controlled ventilation. Implications: We studied the effects of N 2 O on the ratio of alveolar (end-tidal) concentration to inspired concentration of the second gas (enflurane) and on its blood concentration in humans. Nitrous oxide did not affect the alveolar or blood concentration of the second gas under controlled constant volume ventilation. The second gas effect is not a valid concept.