NCT00655980

Vitamins in Nitrous Oxide Study

Pharmacogenetics of Adverse Outcomes After Nitrous Oxide Anesthesia

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 687 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, we want to find out if laughing gas (nitrous oxide) leads to a higher rate of cardiac complications after surgery in patients with a specific genetic profile (mutations in the MTHFR gene) and if this risk can be prevented by giving patients vitamin B12 and folate during surgery.

Detailed description

Background and significance: Recent studies have shown that nitrous oxide (N2O) anesthesia may be associated with an increased risk of adverse cardiovascular outcomes. It is well-known that N2O inhibits vitamin B12-dependent enzymes and as a result increases plasma homocysteine concentrations. Homocysteine has been identified as risk factor for cardiovascular disease. Therefore elevations in homocysteine after N2O may be a causative factor in N2O toxicity. In a previous investigation, we found that patients who carry a homozygous mutation in the MTHFR gene develop higher homocysteine levels after N2O anesthesia than non-carriers. These patients might be at higher risk for adverse cardiac outcomes from N2O. Thus, there may be a pharmacogenetic mechanism to account for the adverse cardiac outcomes from N2O. Moreover, prevention of N2O-increased homocysteine concentrations in these high risk patients by perioperative vitamin B12 and folate supplementation might decrease the incidence of adverse cardiac outcomes. Hypothesis: Patients carrying a homozygous MTHFR 677C\>T or 1298 A\>C variant allele will have a higher incidence rate of postoperative myocardial ischemia after N2O anesthesia \[detected by serial TnI measurements\] due to elevated homocysteine levels than normal "wild-type" non-carriers, and that the incidence rate will be reduced if they receive perioperative vitamin B12/folate supplementation. Primary outcome: Myocardial ischemia in the first 72 hours after surgery (measured by serial troponin and ECGs). Secondary outcome: Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI) Design: Randomized controlled trial. 500 patients will receive N2O during surgery and will be randomized to receive B-vitamins or placebo. 125 patients will receive no N2O and no B-vitamins (control arm). Mendelian randomization of MTHFR genotype. Intervention: IV vitamin B12 (1 mg) and folate (5 mg) pre- and postoperatively Study setting: Barnes-Jewish-Hospital, St. Louis, MO Patients: Patients scheduled for major surgery with or at risk for coronary artery disease

Conditions

• Major Surgery
• Coronary Artery Disease

Interventions

Type	Name	Description
DRUG	Vitamin B12 and folic acid	1 mg vitamin B12 IV 5 mg folic acid IV in 100 ml NS infusion
DRUG	Nitrous oxide and placebo
OTHER	standard of care

Timeline

• Start date: 2008-02-01
• Primary completion: 2016-12-01
• Completion: 2016-12-01
• First posted: 2008-04-10
• Last updated: 2020-10-01
• Results posted: 2020-10-01

Locations

1 site across 1 country: United States