We appreciate the interest Joshi has taken in our post hoc studies of the ENIGMA trial.1As we stated in our article, we measured costs from the perspective of an implementing hospital. We did not consider postdischarge costs. The results of the persistent pain study, conducted at one of the institutions involved in the multicenter ENIGMA trial, was not anticipated and had not yet undergone peer review at the time of publication of the cost-benefit study. It should thus be considered as hypothesis-generating rather than as compelling evidence of a protective effect of nitrous oxide. When considered alongside the results of the ENIGMA trial it is possible that nitrous oxide may have adverse effects in the short-term (infection, cardiac events), but if the patient survives these, then nitrous oxide may be beneficial (for pain).
We must emphasize that at no point have we stated that nitrous oxide has no role in modern anesthetic practice. We have previously concluded that the routine use of nitrous oxide in patients undergoing major surgery should be questioned, and that there is no cogent argument to continue using nitrous oxide on the basis that it is an inexpensive drug. We have emphasized that further studies are needed, and are now measuring long-term pain data in such a trial of 7,000 patients that is currently underway.2
