We read with interest the recent publication by Myles et al.  1on avoidance of nitrous oxide for patients undergoing major surgery. We are divided in our use of nitrous oxide as one of us routinely uses nitrous oxide (J.G.H.) and the other does not (J.S.D.).

We praise the authors for recruiting so many patients to their study, though we question why many of the variables for which this article will be criticized were not controlled more tightly, namely standardized use of antibiotics, antiemetics, and “propofol maintenance anesthesia.” These three factors alone may well have been influential, in part, for some of the different outcomes observed between the two study groups.

We also note there was no standardization of the depth of anesthesia between the two groups. The nitrous oxide–free group had a median end-tidal volatile concentration of 0.87 minimum alveolar concentration (MAC) equivalents, whereas the nitrous oxide group had a median end-tidal volatile concentration of 0.67 MAC equivalents plus 0.64 MAC equivalents of nitrous oxide, 1.31 MAC equivalents in total, with no significant difference in use of other induction sedative drugs (midazolam or opiates) between the groups. The concept of prolonged deep hypnosis resulting in a poorer postoperative outcome has been suggested before,2and we question whether this too may have been a confounding factor in this study.

Finally, although the authors acknowledge the potential for the influence of the differing fractions of inspired oxygen between groups, they do not mention the possibility that the substantial differences in the fraction of inspired nitrogen gas may have affected postoperative pulmonary outcome. Humans have evolved in an atmosphere predominantly made up of nitrogen gas, and nitrogen is well known to splint the alveoli and limit atelectasis3; as little as 20% nitrogen in the anesthetic gas mixture has been shown to lessen atelectasis by nearly 10 times when compared with a pure oxygen mixture,4and one would expect similar findings in a nitrous oxide and oxygen anesthetic. Might many of the respiratory complications observed in this study and which favor the nitrous oxide–free anesthetic actually represent differences in nitrogen use between the two groups?

*University Department of Anaesthesia, Queen’s Medical Centre, Nottingham, United Kingdom. james@dawson.me.uk

Myles PS, Leslie K, Chan MTV, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe E, ENIGMA Trial Group: Avoidance of nitrous oxide for patients undergoing major surgery. Anesthesiology 2007; 107:221–31
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