General Anesthesia
Conditions
Keywords
General Anesthesia, Alzheimers Disease, Cognitive decline
Brief summary
Previous work in animal models suggests that inhalational anesthetic agents may accelerate Alzheimer's disease pathogenesis, but it is unclear to what extent this may happen in humans. Here, the investigators propose to measure Alzheimer's disease-related neural markers in the cerebrospinal fluid (CSF) of patients exposed to anesthesia while undergoing neurosurgical procedures that require lumbar drain placement. Patients will be randomized to either receive inhalation anesthesia with isoflurane or intravenous anesthesia with propofol. CSF and blood samples will each be collected at the induction of anesthesia, and then again ten and twenty-four hours later. CSF samples will be assayed for amyloid beta, tau, and other Alzheimer's disease-associated markers; blood samples will be assayed for serum inflammatory markers and used for genotyping studies. These studies should clarify the effect of common anesthetic agents on Alzheimer's disease related neural markers.
Interventions
DRUGPropofol
patients randomized to the propofol arm of the study will receive general anesthesia with propofol
DRUGIsoflurane
patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age 18 and above * seen in neurosurgical clinic, and scheduled for operative aneurysm repair or other neurosurgical procedure necessitating lumbar drain placement. * ability to speak English. * ability to understand consent forms, and to give informed consent.
Exclusion criteria
* age less than 18 * lumbar drain is not placed * not eligible for one of the anesthetics (inhaled isoflurane or IV propofol) * inmate of a correctional facility (i.e. prisoners). * pregnancy. Pregnancy is ruled out as standard of care before cranial surgery, based on clinical history and/or HCG testing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ratio of cerebrospinal fluid tau to amyloid beta | twenty four hours after the induction of anesthesia |
Secondary
| Measure | Time frame |
|---|---|
| the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race) | up to 24 hrs after induction of anesthesia |
| the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status | up to 24 hrs after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status | up to 24 hrs after induction of anesthesia |
| the relationship between anesthetic exposure and CSF biomarker changes | up to 24 hrs after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal | up to 24 hours after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed | up to 24 hours after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes with genetic polymorphisms in ApoE (apolipoprotein E) and other genes related to inflammation, metabolism, brain function and/or Alzheimer's disease | up to 24 hours after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care | up to 24 hours after induction of anesthesia |
Countries
United States
Outcome results
None listed