The use of laughing gas during noncardiac surgery did not increase the perioperative risk of cardiac injury in patients with or at risk of coronary artery disease (CAD). The results, published in the July issue of Anesthesiology, held up even in patients with a genetic variant that was thought to make them vulnerable.
In previous studies, Peter Nagele, MD, of the anesthesiology department at Washington University in St. Louis, and colleagues analyzed the role of variants in the methylenetetrahydrofolate reductase (MTHFR) gene. Patients with the variants develop higher concentrations of nitrous oxide-induce plasma homocysteines, which have been linked to increased risk of perioperative MI.
Nagele et al designed a double-blind, randomized, placebo controlled trial—Vitamins in Nitrous Oxide—to evaluate whether patients with the genetic variant had an increased risk of perioperative cardiac events after nitrous oxide anesthesia and if B-vitamins mitigated that risk.
They enrolled 500 adult patients diagnosed with CAD or two or more CAD risk factors who were scheduled for elective surgery between 2008 and 2011. Patients were equally divided into one of two groups: nitrous oxide and 1 mg vitamin B12 and 5 mg folic acid or nitrous oxide and placebo. A nonrandomized reference group of 125 patients received anesthesia with no nitrous oxide and no vitamins.
The primary endpoint was incidence of myocardial injury, which they measured by an increase in troponin I within 72 hours of surgery. They collected blood samples and echocardiograms at baseline, end of surgery, and postoperative days one, two and three.
Baseline characteristics for all patient groups were similar. In the 500 randomized patients, 19.6 percent carried the MTHFR C677T or A1298C variant.
Homocysteines concentrations rose in the patient groups who received nitrous oxide. B vitamins blunted the increase but did not affect the rise in troponin I, which was 13.2 percent in the vitamin B group vs. 13.6 percent in the placebo group.
Neither genotype nor B vitamin treatment affected perioperative cardiac outcomes. The incidence rate of increase in troponin I was 11.2 percent in patients with gene variants vs. 14 percent in wild-type and heterozygous patients. Myocardial injury or necrosis was no different in either the vitamin B or placebo groups, regardless of genotype.
“The administration of B-vitamins before and after nitrous oxide anesthesia clearly lowered plasma homocysteine levels, but did not decrease the rate and magnitude of postoperative cardiac troponin increase, or myocardial infarction,” Nagele et al wrote. “We therefore, question the notion that acute nitrous oxide-induced hyperhomocysteinemia has a causal effect on perioperative myocardial ischemia and infarction.”
They expressed surprise at finding the genetic variants had no influence on homocysteine increase but attributed it to dietary folate fortification in the U.S. Consequently, results are not generalizable outside the U.S., they wrote.
They concluded that they found no increased risk in using nitrous oxide. “We therefore, believe that based on current evidence, practitioners who feel that nitrous oxide could be beneficial for their patients should not refrain from administering it because of concern for acute homocysteine increase or MTHFR gene variant.”