Clinical trial NCT00901394: Vitamin B12 and Folate Administration on Homocysteine Concentrations After Nitrous Oxide Anesthesia
Official title: Influence of Preoperative Vitamin B12 and Folate Administration on Homocysteine Concentrations After Nitrous Oxide Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Abnormalities
Keywords: Nitrous oxide
cobalamin
homocysteine
vitamin B12
folate
No specific diseases targeted
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Foundation for Anesthesia Education and Research
First posted: 2009-05-13
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Plasma Total Homocysteine Concentration (tHcy)
timeFrame: Immediately postoperatively and on postoperative day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Peter Nagele, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nagele P, Zeugswetter B, Wiener C, Burger H, Hupfl M, Mittlbock M, Fodinger 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.
citation: Nagele P, Zeugswetter B, Eberle C, Hupfl M, Mittlbock M, Fodinger 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.
citation: 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.