Neuroinflammation and Postoperative Delirium in Cardiac Surgery

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.

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Key information

Conditions

Delirium Cardiac Surgery Confusion Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurocognitive Disorders Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

change in endothelial dysfunction

Time frame: baseline, postoperative day 0, postoperative day 1

biomarker of endothelial dysfunction to be measured at 3 time points
change in blood brain barrier disruption

Time frame: baseline, postoperative day 0, postoperative day 1

biomarker of blood brain barrier disruption to be measured at 3 time points
change in neuronal injury

Time frame: baseline, postoperative day 0, postoperative day 1

biomarker of neuronal injury to be measured at 3 time points

Secondary outcomes

delirium as screened with CAM-ICU

Time frame: 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)

CAM-ICU measured twice daily by research assistant to screen for delirium

Sponsors and collaborators

Lead sponsor

Vanderbilt University

Other

Registry information

Important dates

Study start: 2016
Primary completion: 2017
Study completion: 2017
First posted: Feb 23, 2016
Registry last updated: Sep 17, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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