Abdominal Aneurysm, Aneurysm Stent, Cardiopulmonary Bypass, Thoracic Aneurysm
Conditions
Keywords
thoracoabdominal, aneurysm, open, stent, cardiopulmonary, abdominal, bypass
Brief summary
Alzheimer's disease represents a growing public health problem in developed countries. Although the pathogenesis is not clearly defined, accumulation of extracellular amyloid, neurofibrillary tangles and neuronal loss are the hallmarks of Alzheimer's disease. The effect of anesthetic agents on changes in these proteins in humans is not well characterized, but in-vitro evidence suggests that anesthetic agents can accelerate potential pathogenic mechanisms, such as increasing amyloid formation or rates of apoptosis in cultured cells and increasing amyloid levels in mice. Human data on the effect of anesthetic agents on amyloid and tau proteins is limited to a small series of 11 patients and showed a significant increase in tau levels after exposure to anesthetics. In this study the investigators propose to measure CSF and serum biomarkers in a population of patients with normal CSF dynamics, who are undergoing surgery for repair of a thoracoabdominal aneurysm. The investigators will also obtain preliminary data on whether changes in CSF levels of these proteins are associated with postoperative delirium or cognitive change.
Interventions
DRUGPropofol
Intravenous anesthetic
DRUGisoflurane
Sponsors
National Center for Research Resources (NCRR)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* age 21-100 years of age * Patients presenting for surgical repair of a thoracoabdominal aneurysm * Insertion of a CSF spinal drain for clinically indicated reason
Exclusion criteria
* Patients with pre-existing delirium * Inability to speak and understand English * Severe hearing impairment, resulting in inability to converse * Pregnancy. Pregnancy status will be assessed using a serum pregnancy test during preoperative evaluation as part of the standard of care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Cerebrospinal Fluid (CSF) Levels of Tau | From insertion of spinal drain until removal | Quantitative levels of tau will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane. . |
| Changes in CSF Levels of Amyloid | From insertion of spinal drain until removal | Quantitative levels of amyloid will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM) | Immediately after surgery and at 3 and 12 months post-op | Delirium was measured using the Confusion Assessment Method and the Confusion Assessment Method- Intensive Care Unit (CAM-ICU) based upon post-operative location of patient. The patients were divided into to two groups, patients that had an open thoracoabdominal aneurysm repair versus patients that had stenting of their aneurysms. Patients that had stenting of their aneurysms were also randomized to receive either Propofol or Isoflurane as for their anesthetic. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Inflammatory Markers | From the start of the surgery to 24 hours post-op | Serum inflammatory markers will be compared per anesthetic group, Propofol versus Isoflurane. A sample of 10 individuals from each group will have biomarkers measured |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stent Graft Repair Propofol Intravenous anesthetic - patients will be induced with 1-2mg/kg of Propofol and maintained with 25-200 mcg/kg/min of Propofol.
Propofol: Intravenous anesthetic | 5 |
| Stent Graft Repair Isoflurane standard of care anesthetic - patients will be induced with 1-2 mg/kg of propofol and maintained with 0.5%-1.5% of isoflurane.
isoflurane | 3 |
| Open Repair These patients received no intervention, just standard of care. | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | unsuccessful lumbar drain placement | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Stent Graft Repair Isoflurane | Open Repair | Stent Graft Repair Propofol | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 13 | 71 years STANDARD_DEVIATION 5.3 | 67 years STANDARD_DEVIATION 13 | 65.7 years STANDARD_DEVIATION 11.2 |
| Region of Enrollment United States | 3 participants | 6 participants | 5 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 3 | 0 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 | 0 / 6 |
Outcome results
Primary
Changes in Cerebrospinal Fluid (CSF) Levels of Tau
Quantitative levels of tau will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane. .
Time frame: From insertion of spinal drain until removal
Population: The data for changes in CSF levels of tau are not available. The study did not have adequate funding to appropriately measure these variables.
Primary
Changes in CSF Levels of Amyloid
Quantitative levels of amyloid will be measured using ELISA assay technique in pg/ml to compare the differences between the group receiving Propofol and the groups receiving Isoflurane.
Time frame: From insertion of spinal drain until removal
Population: The data for changes in CSF levels of amyloid are not available. The study did not have adequate funding to appropriately measure these variables.
Secondary
Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM)
Delirium was measured using the Confusion Assessment Method and the Confusion Assessment Method- Intensive Care Unit (CAM-ICU) based upon post-operative location of patient. The patients were divided into to two groups, patients that had an open thoracoabdominal aneurysm repair versus patients that had stenting of their aneurysms. Patients that had stenting of their aneurysms were also randomized to receive either Propofol or Isoflurane as for their anesthetic.
Time frame: Immediately after surgery and at 3 and 12 months post-op
Population: Of the 6 patients that received an open thoracoabdominal aneurysm repair 2 were found to have delirium. Of the 5 subjects that had stenting and received Propofol as their primary anesthetic, 0 were found to have delirium. Of the 3 stenting subjects that received Isoflurane as their primary anesthetic, 1 were found to have delirium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM) | 2 participants |
| Isoflurane | Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM) | 0 participants |
| Stent Graft Aneurysm Repair Isoflurane | Number of Participants With Delirium as Assessed by the Confusion Assessment Method (CAM) | 1 participants |
Other Pre-specified
Serum Inflammatory Markers
Serum inflammatory markers will be compared per anesthetic group, Propofol versus Isoflurane. A sample of 10 individuals from each group will have biomarkers measured
Time frame: From the start of the surgery to 24 hours post-op
Population: No data is available for serum inflammatory markers. The study did not have adequate funding to appropriately measure these variables.