Clinical pharmacology of nitrous oxide: an argument for its continued use

We tested the hypothesis that the administration of nitrous oxide (N2O) causes major (e.g., myocardial infarction, neuronal injury, hypoxemia, infection, death) or minor (e.g., nausea, vomiting, headache, earache) untoward effects in patients requiring anesthesia for 1.5-4 h. Given the higher morbidity and mortality associated with aging, we also tested whether aging increased any untoward effect of N2O. Finally, we investigated whether the substitution of N2O for a fraction of the anesthesia supplied by isoflurane altered the latter's pharmacologic effects. We studied 270 patients scheduled for elective total hip arthroplasty (n = 100), carotid endarterectomy (n = 70), or transsphenoidal hypophysectomy (n = 100) who were randomly assigned within each surgical group to receive isoflurane with or without 60% N2O. Regardless of patient age, we found no difference in major or minor untoward outcomes between anesthetic groups, nor a trend to suggest that a larger data cohort would reveal a significant adverse effect of N2O. The addition of N2O administration decreased the isoflurane requirement for clinical anesthesia but did not alter most of the clinical variables measured in practice, including blood pressure, heart rate, rate of recovery from anesthesia, development of postoperative pain, patient satisfaction with anesthesia, or duration of anesthesia or of hospitalization. Patients given N2O were no more likely to dream during anesthesia, remember events during anesthesia, or be frightened by those events. Our results support the continued use of N2O to anesthetize patients for elective surgery.