This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.

Background This study sought to determine if preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major non-cardiac surgery when compared to standard risk indices. Methods In this ancillary study to the Vitamins in Nitrous Oxide (VINO) trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n=572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first three postoperative days. hs-cTn was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated based on ROC statistics. Biomarker risk prediction was compared to Lee’s Revised Cardiac Risk Index (RCRI) using standard methods and net reclassification index (NRI). Results The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 (5.2%), AUC ROC increased from 0.590 to 0.716 with a 0.66 NRI [95% CI 0.32 – 0.99] p<0.001). Using 108 ng/L as cutoff for NT-proBNP improved sensitivity compared to 300 ng/L (0.87 vs. 0.53). Sensitivity, specificity, positive and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09 and 0.97, and 0.53, 0.68, 0.08, 0.96 for NT-proBNP. Conclusions The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves prediction of adverse cardiac events in the immediate postoperative period after major non-cardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a “rule-out” test to confirm low risk of postoperative MI.