Puzzling ENIGMA: Cost-Benefit Analysis of Nitrous Oxide

To the Editor: 

I read with interest the article by Graham et al.  1In this study the authors performed a retrospective cost-analysis of data from the ENIGMA trial, in which patients randomly received nitrous oxide nitrous oxide-based anesthesia (70% N²O and 30% O²) or nitrous oxide-free anesthesia (80% O²and 20% N²). The authors concluded, “Despite nitrous oxide reducing the consumption of more expensive potent inhalational agent, there were marked additional costs associated with its use in adult patients undergoing major surgery because of an increased rate of complications. There is no cogent argument to continue using nitrous oxide on the basis that it is an inexpensive drug.”

It is interesting that in this cost-analysis the authors neglected to include one of the benefits of nitrous oxide: analgesia. In fact, in another study, again from a retrospective analysis of the ENIGMA trial data,2the same authors reported that intraoperative administration of nitrous oxide reduced the risk of chronic postsurgical pain by more than half. The authors also found that chronic postsurgical pain was common after major noncardiac surgery. The authors state, “The presence of chronic postsurgical pain cannot be considered as a trivial event. Our data indicate that it affects all dimensions of general health status, including social function, physical activities, emotion, and mental health. Chronic postsurgical pain also has a major impact on patients' daily living, including loss of productivity, an increase in medical expenses, and costs of repeated hospital admissions.”

It is highly likely that a cost-benefit analysis that includes the benefits of nitrous oxide (i.e. , reduced chronic postsurgical pain) may tilt the balance toward nitrous oxide. I think the authors may have rushed to conclude that nitrous oxide has no role in modern anesthetic practice. Unfortunately, such selective reporting may inappropriately dissuade anesthesia practitioners from using nitrous oxide and deprive our patients from some potential long-term benefits from its use.