Safety of Nitrous Oxide Anesthesia in a Selected Group of Patients Undergoing Neurosurgery: An Exploratory Subgroup Analysis of the ENIGMA Trials

BACKGROUND: The Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia (ENIGMA)-I and ENIGMA-II were randomized clinical trials that assessed the safety of nitrous oxide anesthesia in patients undergoing noncardiac surgery. In this study, we performed an exploratory pooled analysis of both ENIGMA trials to assess the safety of nitrous oxide in a selected group of patients undergoing neurosurgery. METHODS: Data from each ENIGMA trial were collated into a single database. Information regarding patient demographics, comorbidities, medication use, anesthesia, surgical procedure, and postoperative complications was extracted. Multivariate logistic regression was conducted for postoperative complications to assess the risk associated with nitrous oxide. RESULTS: A total of 830 patients were included in our analysis: 417 received nitrous oxide anesthesia, and 413 received nitrous oxide-free anesthesia. Baseline patient and perioperative characteristics were comparable. Procedural data were available for 535 patients (64%); of these, 507 (95%) underwent spinal neurosurgery and 28 (5%) underwent cranial neurosurgery. Patients in the nitrous oxide group had lower inspired oxygen concentration (30% vs. 38%; P<0.001) and end-tidal volatile agent concentration (0.56 vs. 0.89 minimal alveolar concentration equivalents; P<0.001) compared with the nitrous oxide-free group. Use of nitrous oxide was not associated with increased risk of postoperative complications (myocardial infarction, cardiac arrest, stroke, infection, severe vomiting, fever, pneumonia, pneumothorax, blood transfusion, venous thromboembolism, or death) (odds ratio: 1.22; 95% confidence interval: 0.89-1.65; P=0.22) or prolonged length of hospital stay (median 5.0 vs. 4.2 d for nitrous oxide and nitrous oxide-free groups; P=0.28). CONCLUSION: Nitrous oxide did not increase the risk of postoperative complications or prolonged length of hospital stay in the neurosurgical cohort enrolled in the ENIGMA-I and ENIGMA-II trials.