Neuroinflammation and Postoperative Delirium in Cardiac Surgery
| Status: | Completed |
|---|---|
| Conditions: | Cardiology, Neurology, Psychiatric |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/19/2018 |
| Start Date: | January 2016 |
| End Date: | March 2017 |
Up to 50% of patients over 60 years old develop postoperative delirium following cardiac
surgery. Delirium increases morbidity and mortality, and may lead to long-term cognitive
impairment similar to patients with a diagnosis of Alzheimer's disease. The underlying
mechanisms behind delirium are not understood, and therefore the current prevention and
treatment strategies are inadequate. Several hypotheses exist for the pathophysiology of
delirium, one of which is the role of neuroinflammation. The stress associated with high-risk
procedures such as cardiac surgery may lead to systemic inflammation causing endothelial
dysfunction and disruption of the blood brain barrier (BBB). When this occurs, the brain is
susceptible to neuronal injury via neuroinflammation after which a state of delirium may
ensue. To characterize the mechanisms of neuroinflammation in delirium, the investigators
will explore the biomarkers most closely linked to each step of the proposed pathway.
surgery. Delirium increases morbidity and mortality, and may lead to long-term cognitive
impairment similar to patients with a diagnosis of Alzheimer's disease. The underlying
mechanisms behind delirium are not understood, and therefore the current prevention and
treatment strategies are inadequate. Several hypotheses exist for the pathophysiology of
delirium, one of which is the role of neuroinflammation. The stress associated with high-risk
procedures such as cardiac surgery may lead to systemic inflammation causing endothelial
dysfunction and disruption of the blood brain barrier (BBB). When this occurs, the brain is
susceptible to neuronal injury via neuroinflammation after which a state of delirium may
ensue. To characterize the mechanisms of neuroinflammation in delirium, the investigators
will explore the biomarkers most closely linked to each step of the proposed pathway.
Aim 1a. Test the hypothesis that endothelial injury is associated with delirium. The
investigators hypothesize that endothelial dysfunction is associated with an increased
incidence of delirium after cardiac surgery. To test this hypothesis, the investigators will
measure biomarkers from subjects undergoing cardiac surgery. Blood samples from three time
points [baseline, upon arrival to the intensive care unit (ICU), and postoperative day 1
(POD1)] will be analyzed and compared between patients that did and did not develop
postoperative delirium.
Aim 1b. Test the hypothesis that BBB disruption is associated with delirium. The
investigators hypothesize that disruption in the BBB is associated with an increased
incidence of delirium after cardiac surgery. To test this hypothesis, the investigators will
measure levels of biomarkers at baseline, upon arrival to the ICU, and on POD1.
Aim 1c. Test the hypothesis that neuronal injury is associated with delirium. The
investigators hypothesize that neuronal injury is associated with an increased incidence of
delirium after cardiac surgery. To test this hypothesis, the investigators will measure
levels of biomarkers at baseline, upon arrival to the ICU, and on POD1.
investigators hypothesize that endothelial dysfunction is associated with an increased
incidence of delirium after cardiac surgery. To test this hypothesis, the investigators will
measure biomarkers from subjects undergoing cardiac surgery. Blood samples from three time
points [baseline, upon arrival to the intensive care unit (ICU), and postoperative day 1
(POD1)] will be analyzed and compared between patients that did and did not develop
postoperative delirium.
Aim 1b. Test the hypothesis that BBB disruption is associated with delirium. The
investigators hypothesize that disruption in the BBB is associated with an increased
incidence of delirium after cardiac surgery. To test this hypothesis, the investigators will
measure levels of biomarkers at baseline, upon arrival to the ICU, and on POD1.
Aim 1c. Test the hypothesis that neuronal injury is associated with delirium. The
investigators hypothesize that neuronal injury is associated with an increased incidence of
delirium after cardiac surgery. To test this hypothesis, the investigators will measure
levels of biomarkers at baseline, upon arrival to the ICU, and on POD1.
Inclusion Criteria:
- open heart surgery
Exclusion Criteria:
- acute coronary syndrome with troponin leak or unrelenting angina
- liver dysfunction (transaminases 2x normal)
- history of myopathy or liver dysfunction on prior statin therapy
- use of potent CYP3A4 inhibitors such as antifungal azoles, macrolide antibiotics, HIV
protease inhibitors, and nefazodone.
- pregnancy or breast feeding
- cyclosporine use
- dialysis
- history of kidney transplant
- fibrate users who cannot stop fibrate use
We found this trial at
1
site
1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Principal Investigator: Jason B O'Neal, M.D.
Phone: 252-292-6792
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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