Vitamin B12 and Folate Administration on Homocysteine Concentrations After Nitrous Oxide Anesthesia

Study Overview
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Brief Summary
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The goal of this study is to find out if giving intravenous B-vitamins before general anesthesia with nitrous oxide prevents the increase in homocysteine, a metabolite that has been linked to cardiovascular complications.

Detailed Description
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Patients will be randomized into the following arms: Arm A: patients will receive N2O (60% N2O/40% O2) in an open-label fashion during surgery and vitamin supplementation (vitamin B12, 1 mg, and folate, 5 mg) before surgery. Arm B: patients will receive N2O 60% N2O/40% O2) in an open-label fashion during surgery and placebo before and after surgery. Arm C: patients will not receive N2O, vitamin supplementation, or placebo during/before surgery. Patients in this arm will not be randomized. Patients will have blood drawn (total of 1-2 teaspoons over 3 days). We will take these samples before their surgery, when their surgery is completed, and in the morning of post-operative day 1. We will be checking their troponin I and troponin T, homocysteine, Vitamin B12, and folate levels. We will also perform a 12-lead EKG. Before and after surgery for patients in Arm A or B, will receive either vitamin B12 (1 mg) and folic acid (5 mg) (or placebo) added to their IV infusion. We also plan to use a non-invasive test known as a nerve conduction study to measure the function of their nerve system. Briefly, 2 small electrodes are attached to their skin over a nerve and, like an EKG, faint electrical pulses are generated and recorded. A typical nerve conduction measurement lasts about 10 minutes. After the patients surgery we will do genetic testing of MTHFR genotype. All study samples have been collected. Of note: there were no secondary outcomes.

Official Title
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Influence of Preoperative Vitamin B12 and Folate Administration on Homocysteine Concentrations After Nitrous Oxide Anesthesia

Conditions
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Cardiovascular Abnormalities

Intervention / Treatment
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* Drug: B12-Folic Acid, nitrous oxide
* Drug: Nitrous oxide (NO) and placebo
* Other: Placebo
* Other: oxygen nitrogen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients scheduled for elective surgery with expected duration > 2 hours Healthy patients undergoing moderate surgery where the use of N2O is unproblematic Exclusion Criteria: Contraindication against N2O (pneumothorax, mechanical bowel obstruction, middle ear occlusion, laparoscopic surgery, raised intracranial pressure) Patients requiring supplemental oxygen Urgent or emergent surgery Patients with vitamin B12 or folate deficiency or megaloblastic anemia Patients with seizure disorder (epilepsy) Allergy or hypersensitivity against IV cobalamin or folate Patients with Leber's disease (hereditary optic nerve atrophy) Patients taking supplemental vitamin B12 or folate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment 1<br>B12-Folic acid, nitrous oxide | Drug: B12-Folic Acid, nitrous oxide<br>* IV vitamin B12 (cyanocobalamin) 1 mg, single administration over 30 min. IV folic acid, 5 mg, single administration over 30 min. Both diluted in 250 ml normal saline.<br>* Other names: b supplements;Drug: Nitrous oxide (NO) and placebo<br>* 60% nitrous oxide anesthesia plus saline<br>* Other names: nitrous oxide;|
| Active Comparator: Treatment 2<br>Nitrous oxide (NO) and placebo | Drug: Nitrous oxide (NO) and placebo<br>* 60% nitrous oxide anesthesia plus saline<br>* Other names: nitrous oxide;Other: Placebo<br>* Saline<br>* Other names: saline;|
| Placebo Comparator: Control group<br>oxygen nitrogen | Other: Placebo<br>* Saline<br>* Other names: saline;Other: oxygen nitrogen<br>* 60% air and oxygen mix.<br>* Other names: air;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Total Homocysteine Concentration (tHcy) | Difference between baseline (pre-operative) and peak postoperative (i.e., maximum of postoperative value obtained within 30 minutes after anesthesia end time and morning of post-operative day 1) tHcy concentration . Of note: there were no secondary outcomes. | Immediately postoperatively and on postoperative day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitrous oxide, cobalamin, homocysteine, vitamin B12, folate, No specific diseases targeted