Influence of Nitrous Oxide Anesthesia, B-Vitamins, andMTHFRGene Polymorphisms on Perioperative Cardiac Events

Abstract

Background Nitrous oxide causes an acute increase in plasma homocysteine that is more pronounced in patients with the MTHFR C677T or A1298C gene variant. In this randomized controlled trial we sought to determine if patients carrying the MTHFR C677T or A1298C variant had a higher risk for perioperative cardiac events after nitrous oxide anesthesia and if this risk could be mitigated by B-vitamins. Methods We randomized adult patients with cardiac risk factors undergoing noncardiac surgery to receive nitrous oxide plus intravenous B-vitamins before and after surgery or to nitrous oxide and placebo. Serial cardiac biomarkers and 12-lead electrocardiograms were obtained. The primary study endpoint was the incidence of myocardial injury, as defined by cardiac troponin I elevation within the first 72 hours after surgery. Results A total of 500 patients completed the trial. Patients who were homozygous for either MTHFR C677T or A1298C gene variant (n= 98; 19.6%) had no increased rate of postoperative cardiac troponin I elevation compared to wild-type and heterozygous patients (11.2% vs. 14.0%; relative risk 0.96, 95% CI 0.85 to 1.07, p=0.48). B-vitamins blunted the rise in homocysteine, but had no effect on cardiac troponin I elevation compared to patients receiving placebo (13.2% vs. 13.6%; relative risk 1.02, 95% CI 0.78 to 1.32, p=0.91). Conclusions Neither MTHFR C677T and A1298C gene variant nor acute homocysteine increase are associated with perioperative cardiac troponin elevation after nitrousoxide anesthesia. B-vitamins blunt nitrous oxide-induced homocysteine increase but have no effect on cardiac troponin elevation.

Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP

“…A detailed description of the trial methods and main results have been published elsewhere. (22) VINO enrolled 625 adult patients with either known coronary artery disease or multiple risk factors for coronary artery disease who were scheduled for major non-cardiac surgery under general anesthesia. Patients were randomly assigned to receive nitrous oxide and B-vitamins (250 patients) or nitrous oxide and placebo (250 patients).…”

“…The primary purpose of VINO was to investigate the effects of nitrous oxide plus B-vitamins on perioperative cardiac events. (22)…”

The Effect of Nitrous Oxide Anesthesia on Early Postoperative Opioid Consumption and Pain

“…In the VINO trial, 11 500 patients undergoing noncardiac surgery were randomly allocated to receive either 60% N 2 O/40% O 2 plus a vitamin B infusion (n=250) or 60% N 2 O/40% O 2 plus placebo infusion (n=250). A nonrandomized reference group of 125 patients without N 2 O was concurrently enrolled.…”

“…3 We recently completed a clinical trial were patients undergoing non-cardiac surgery received N 2 O or N 2 O-free anesthesia in a nonrandomized fashion [the Vitamins In Nitrous Oxide (VINO) Trial; clinicaltrials.gov, NCT00655980]. 11 In this post-hoc analysis, we compared early postsurgical opioid consumption and pain in patients who received N 2 O during general anesthesia with patients who did not receive N 2 O during general anesthesia.…”

In Reply

“…The Vitamins in Nitrous Oxide (VINO) trial analysis fully adhered to the intention-to-treat principle. 1 The intervention in the VINO trial was an infusion of B-vitamins or placebo. The 57 patients that were excluded from the analysis were withdrawn from the study before receiving any treatment and therefore had to be excluded.…”