Laughing gas doesn’t boost heart attack risk

WASHINGTON U. – ST. LOUIS (US) — Researchers followed 500 patients at elevated risk of heart attack and found that using nitrous oxide during surgery did not increase heart attack risk.

Nitrous oxide—best known as laughing gas—is one of the world’s oldest and most widely used anesthetics. Despite its popularity, however, experts have questioned its impact on the risk of a heart attack during surgery or soon afterward. But those fears are unfounded, a new study in the journal Anesthesiology concludes.

“It’s been known for quite a while that laughing gas inactivates vitamin B12 and, by doing so, increases blood levels of the amino acid homocysteine,” says lead author Peter Nagele, assistant professor of anesthesiology and genetics at Washington University School of Medicine. “That was thought to raise the risk of a heart attack during and after surgery, but we found no evidence of that in this study.”

Nitrous oxide normally is used as an adjunct during general anesthesia because by itself the drug isn’t strong enough to keep patients unconscious during surgical procedures. The drug’s influence on B vitamins and homocysteine is unrelated to its anesthetic effects.


Nagele and his colleagues followed 500 surgery patients at Barnes-Jewish Hospital in St. Louis who had been diagnosed with coronary artery disease, heart failure, or other health problems that could contribute to a heart attack. All subjects in the study had noncardiac surgery and received nitrous oxide anesthesia.

Vitamin B12

The patients were divided into two groups. Half received intravenous vitamin B12 and folic acid to help prevent homocysteine levels from rising during surgery. The others did not get the intravenous B vitamins.

“There were no differences between the groups with regard to heart attack risk,” Nagele says. “The B vitamins kept homocysteine levels from rising, but that didn’t influence heart attack risk.”

To detect heart attacks during and after surgery, the researchers monitored a marker of heart damage, cardiac troponin I, for 72 hours. A rise in troponin levels indicates damage to the heart. But they found no link between patients’ homocysteine and troponin levels.

Genetic differences

The study also looked at gene variations that naturally lead to elevated homocysteine. Individuals with common variants in the MTHFR gene already make excess homocysteine. If people with those variants then get nitrous oxide anesthesia, their levels can climb even higher.

But only 3.1 percent of patients with the high-risk genetic variants had heart attacks during or after surgery, compared with 4.7 percent of the patients who didn’t have the risky variants. Neither the gene variation nor treatment with B vitamins had an effect on troponin levels following surgery.

“People who had the gene variant did, indeed, develop very high levels of homocysteine in response to nitrous oxide,” Nagele says. “So the question is whether those patients would be at a higher risk for heart attack, and that answer is no.”

The National Institute for General Medical Sciences and the National Institute for Research Resources of the National Institutes of Health funded the research. It also was supported by the Foundation for Anesthesia Education and Research, as well as Roche Diagnostics, which provided high-sensitivity troponin T assays and funding to cover the costs of running those tests but had no role in the design of the study, data collection or analysis, or manuscript preparation and submission.

Source: Washington University in St. Louis