Laughing gas is associated with increased risk for perioperative cardiac events

A clinical trial published in the July issue of Anesthesiology may shed some light on whether nitrous oxide ("laughing gas") causes an increased risk for cardiac events, including heart attacks after surgery, particularly among high-risk patients. Some previous studies show nitrous oxide, one of the oldest and most widely used general anesthetics in the world, has been associated with an increased risk for perioperative cardiac events.

In the Vitamins in Nitrous Oxide (VINO) trial, the authors asked if patients with a certain genetic background that predisposed them to higher plasma homocysteine levels (MTHFR gene variants) had a higher risk of postoperative cardiac events when they received nitrous oxide and whether this risk could be ameliorated with prophylactic administration of B-vitamins.

"Since patients with the MTHFR C677T or A1298C gene variants may be at higher risk for perioperative cardiac events, we wanted to determine whether B-vitamins could help alleviate this risk," said lead study author Peter Nagele, M.D., M.Sc., assistant professor, Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis. "As B-vitamins such as vitamin B12 and folic acid are known to lower plasma homocysteine concentrations, it was important to determine their role in patient cardiac outcomes."

About the study

In a clinical trial, sponsored in part by the Foundation for Anesthesia Education and Research (FAER) and the National Institutes of Health (NIH), the researchers studied 500 adult patients with cardiac risk factors undergoing non-cardiac surgery. Patients received either intravenous B-vitamins and nitrous oxide, or placebo and nitrous oxide and were followed for three days after surgery to detect cardiac events.

The authors found patients with the MTHFR C677T or A1298C gene variant did not experience an increased risk for postoperative cardiac events. Furthermore, while B-vitamins lowered the rise in plasma homocysteine concentrations, the vitamins had no effect on cardiac events compared to the placebo group. Lastly, the researchers discovered that acute increases in plasma homocysteine concentrations were not associated with cardiac risk, dispelling the notion that the acute increase in homocysteine seen in patients who receive nitrous oxide is related to cardiac risk during and after surgery.

In an accompanying editorial, Paul S. Myles, M.D., Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Victoria, Australia, recognized the study's ability to determine the likelihood that nitrous oxide may not lead to cardiovascular events.

"Future research needs to be done on larger-scale trials to determine whether there is benefit or harm from using nitrous oxide in patients, and what that specific benefit or harm is," said Dr. Myles.