Neuroinflammation and Postoperative Delirium in Cardiac Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Neuroinflammation and Postoperative Delirium in Cardiac Surgery

Conditions
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Delirium, Cardiac Surgery

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiac surgery patients<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in endothelial dysfunction | biomarker of endothelial dysfunction to be measured at 3 time points | baseline, postoperative day 0, postoperative day 1 | 
| change in blood brain barrier disruption | biomarker of blood brain barrier disruption to be measured at 3 time points | baseline, postoperative day 0, postoperative day 1 | 
| change in neuronal injury | biomarker of neuronal injury to be measured at 3 time points | baseline, postoperative day 0, postoperative day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delirium as screened with CAM-ICU | CAM-ICU measured twice daily by research assistant to screen for delirium | twice daily after surgery until discharge from ICU (12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, 96 hours, continuing every 12 hours up to 24 weeks) |