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

Cardiovascular Abnormalities Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00901394
• Other study ID #: 09-0074
• Status: Completed
• Phase: N/A
• Start date: March 2009
• Est. completion date: January 2010

Study information

• Verified date: August 2020
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Abnormalities

Intervention

Drug:
• B12-Folic Acid, nitrous oxide
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.
• Nitrous oxide (NO) and placebo
60% nitrous oxide anesthesia plus saline

Other:
• Placebo
Saline
• oxygen nitrogen
60% air and oxygen mix.

Locations

Country	Name	City	State
United States	Barnes Jewish Hospital	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Foundation for Anesthesia Education and Research

Country where clinical trial is conducted

United States, 

References & Publications (3)

Myles PS, Chan MT, Kaye DM, McIlroy DR, Lau CW, Symons JA, Chen S. Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function. Anesthesiology. 2008 Oct;109(4):657-63. doi: 10.1097/ALN.0b013e31818629db. — View Citation

Nagele P, Zeugswetter B, Eberle C, Hüpfl M, Mittlböck M, Födinger M. A common gene variant in methionine synthase reductase is not associated with peak homocysteine concentrations after nitrous oxide anesthesia. Pharmacogenet Genomics. 2009 May;19(5):325-9. doi: 10.1097/FPC.0b013e328328d54c. — View Citation

Nagele P, Zeugswetter B, Wiener C, Burger H, Hüpfl M, Mittlböck M, Födinger M. Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia. Anesthesiology. 2008 Jul;109(1):36-43. doi: 10.1097/ALN.0b013e318178820b. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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