Interaction of Cobalamin Status With Nitrous Oxide in Relation to Postoperative Cognitive Changes in the Elderly
Status:
Completed
Trial end date:
2008-08-01
Target enrollment:
Participant gender:
Summary
Low cobalamin (vitamin B12) levels are frequent in the elderly. Most often they reflect a
mild metabolic abnormality without clinical symptoms (subclinical cobalamin deficiency). It
is unclear if these elderly people require medical intervention, unlike that small minority
with clinical symptoms which can progress and create severe blood or nervous system problems.
The study aims to determine if nitrous oxide (N2O), a common anesthetic agent, worsens
cobalamin status in elderly patients with unrecognized subclinical cobalamin deficiency. The
reason for concern is that N2O inactivates cobalamin and can aggravate the clinical picture
of patients who already have clinical manifestations of cobalamin deficiency. The elderly are
known to have an increased risk of developing mental changes after surgery and it may be that
sometimes these result from aggravation of subclinical cobalamin deficiency.
The study recruits people over the age of 60 years who are undergoing clinically indicated
elective surgery requiring general anesthesia for more than 1 hour. Patients meeting
exclusion and inclusion criteria are randomized to receive either a standard anesthetic
regimen that includes N2O or a nearly identical one without N2O. Before surgery and 2 weeks
and 4 weeks after surgery, each patient undergoes (1) a broad battery of tests of cognition
and mood and (2) blood tests measuring cobalamin, folate and homocysteine-methionine
metabolism to determine whether they have any subtle biochemical impairment of cobalamin
status. DNA from blood cells is also tested for the presence of common mutations that affect
key enzymes in those metabolic pathways. A brief testing for postoperative delirium is also
done 2 hours after surgery.
The patient subgroups' are analyzed for neuropsychologic changes over time, using the
preoperative test as the baseline for all comparisons, and associations of those changes with
metabolic, genetic, demographic and clinical data.
The primary question is what effect routine N2O exposure has on the latter compared with
non-N2O anesthesia in elderly people who either have or do not have subclinical cobalamin
deficiency. It will help answer whether or not the combination can help explain the increased
risk of cognitive problems after surgery in elderly patients, and by extension whether
preoperative cobalamin testing and treatment may be indicated in the elderly. It will also
test whether genetic predisposition affects the described problems.
Phase:
N/A
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Treatments:
Anesthetics Hydroxocobalamin Nitrous Oxide Vitamin B 12