Interaction of Cobalamin Status With Nitrous Oxide in Relation to Postoperative Cognitive Changes in the Elderly
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|ClinicalTrials.gov Identifier: NCT00212147|
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : August 8, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Avitaminosis Delirium, Dementia, Amnestic, Cognitive Disorders||Drug: General anesthesia with nitrous oxide Drug: General anesthesia without nitrous oxide||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||444 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Subtle Disturbances of Cobalamin Status|
|Study Start Date :||September 2003|
|Actual Primary Completion Date :||August 2008|
|Actual Study Completion Date :||August 2008|
|Experimental: General anesthesia with nitrous oxide||
Drug: General anesthesia with nitrous oxide
|Active Comparator: General anesthesia without nitrous oxide||
Drug: General anesthesia without nitrous oxide
- neuropsychologic performance changes [ Time Frame: 4 weeks ]
- metabolic changes [ Time Frame: 4 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00212147
|United States, New York|
|New York Methodist Hospital|
|Brooklyn, New York, United States, 11215|
|WeillMedical College of Cornell University|
|New York, New York, United States, 10021|
|Principal Investigator:||Ralph Carmel, MD||New York Presbyterian Brooklyn Methodist Hospital|