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The Second Gas Effect is Not Statistically Valid

Uda, Rumiko, MD, PhD; Onaka, Masahiko, MD, PhD.; Okuno, Takashi, MD; Mori, Hidemaro, MD PhD

doi: 10.1097/00000539-200203000-00061
Letters To The Editor: Letters & Announcements

Department of Anaesthesiology, Osaka Medical College

Takatsuki, Osaka, Japan

To the Editor:

We have taken a keen interest in the discussion into the validity of the second gas effect since Sun et al. (1) published their findings and the subsequent rebuke by Taheri and Eger II (2) was published. When referring to the original data presented by Epstein et al. (3), unfortunately, no statistical significant difference can be observed over time in the ratio of alveolar (end-tidal) concentration and inspired concentration (FA/FI) between administering 0.5% halothane with 70% N2O and 0.5% halothane with 10% N2O by means of two-way repeated-measures analysis of variance (n = 5, P = 0.5877, Stat View version 5.0; SAS Institute, Cary, NC) at a statistical significance of P < 0.05. Quite to the contrary, the concentration effect is in fact validated by the same method. When comparing the two groups using a paired Student’s t-test, the 70% N2O should first be administered for 1 min before a sample is taken. The 10% N2O can then be administered for 1 min in the same dog, but only after the 70% N2O has been flushed out. For 2-min measurements, different dogs should be used. With Wilcoxon’s signed-ranks test if n ≥ 6, P values of approximately 0.04 at <5% probability were recorded at 2, 3, and 4 min (Table 1).

Table 1

Table 1

We propose that the reasoning for the second gas effect is insufficiently compelling in view of the methodological approach. The second gas effect would seem to be more difficult to verify clinically because all the factors, including statistics likely to produce the effect, are reproduced in the preparation. We believe most anesthesiologists are much more interested in how rapidly a patient is anesthetized than at the rate of increase in the FA/FI ratio even if the effect is marked.

Rumiko Uda, MD, PhD

Masahiko Onaka, MD, PhD.

Takashi Okuno, MD

Hidemaro Mori, MD, PhD

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1. Sun X-G, Su F, Shi Y-Q, Lee C. The “second gas effect” is not a valid concept. Anesth Analg 1999; 88: 188–92.
2. Taheri S, Eger EI II. A demonstration of the concentration and second gas effects in humans anesthetized with nitrous oxide and desflurane. Anesth Analg 1999; 89: 774–80.
3. Epstein RM, Rackow H, Salanitre E, Wolf GL. Influence of the concentration effect on the uptake of anesthetic mixtures: the second gas effect. Anesthesiology 1964; 25: 364–71.
© 2002 International Anesthesia Research Society