Out-of-hospital Cardiac Arrest (OHCA) Biomarkers

Study Overview
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Brief Summary
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Few early prognostic indicators are currently available for patients' families and clinicians following out of hospital cardiac arrest (OHCA), and blood biomarkers may be of prognostic value in these cases. Brain tissue is highly dependent upon aerobic respiration, and oxygen deprivation result in irreversible neuronal cell injury. Peptides released into the blood by injured neuronal cells can be measured to estimate degree of injury, and potentially predict long term neurological outcome.

Detailed Description
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Aggressive treatment for patients with out-of-hospital cardiac arrest (OHCA) can result in return of spontaneous circulation (ROSC). However, prognosis for these patients remains poor, with low rates of survival to hospital admission and low rates of survival to hospital discharge. Furthermore, due to the exquisite sensitivity to hypoxic injury of neural tissue (dependent on aerobic respiration) relative to that of cardiac muscle, patients for whom ROSC can be obtained often suffer devastating neurological injury, with potential poor long-term neurological outcome. In some ischemic processes, for example, myocardial infarction, rapid measurement of cardiac biomarkers (e.g. Troponin isoform) is invaluable to current diagnosis and management. However, with regards to ischemic brain injury, there is currently no rapid, definitive diagnostic test to prognosticate outcome in OHCA. Biomarkers measurable in blood would have vital applications in prognosis and clinical research of neurological outcome in OHCA. Other groups have studied the neurological predictive values of biomarkers after OHCA. A variety of proteins including S100B, neuron-specific enolase, and G-FAP, co-peptin, Tau, neurofilament light/ heavy chain, and secretoneurin have been proposed as potential biomarkers of neurological outcome at OHCA. Unfortunately, many of these have been shown to have several drawbacks. For example, some lack specificity due to being released during resuscitation (e.g., S100B is found extracerebrally in muscle, adipocytes, and chondrocytes, creating a confounding factor in CA patients receiving chest compressions). Others have lacked sufficient sensitivity in the prognosticating of neurological outcome (ref). Furthermore, there is a paucity of human studies in cardiac arrest on newer biomarkers that have been studied in other acute brain injury disease processes that could potentially serve as candidate biomarkers predicting neurological outcome at post cardiac arrest hypoxic brain injuries. Biomarkers such as UCH-L1, SBDP, and MBP have not been studied in a OHCA cohort. The Investigator therefore propose a prospective, observational study in which the investigator will incorporate a minimally invasive and minimal risk measurement of blood biomarkers at time of ROSC. This would be done by drawing blood at ROSC (0-59mins), and additional blood draws at hours 6, 12, 18, 24, 48, 72, and on day 4, 5, and 6. The Investigator will then determine whether biomarker levels correlates with survival to hospital admission, survival to hospital discharge, and functional neurologic outcome at discharge and at 6 months. The Investigator intend to sample patients that present to the emergency department with non-CA chest pain in our study as well, which will allow us to draw stable inferences.

Official Title
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Predicting Neurological Outcome Following Out of Hospital Cardiac Arrest (OHCA) by Quantitative Measurement of Serial Serum Biomarkers of Brain Injury.

Conditions
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Neurological Outcome, Cardiac Arrest, Out-Of-Hospital Cardiac Arrest, Brain Anoxia Ischemia, Hypoxia, Brain, Hypoxia-Ischemia, Brain, Cardiac Arrest With Successful Resuscitation, Cardiac Arrest, Out-Of-Hospital, Brain Injuries

Intervention / Treatment
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* Procedure: blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - >18 years old Study cohort: Non-traumatic out of hospital cardiac arrest Control cohort: Chest pain of non-cardiac etiology Exclusion Criteria: Both cohorts: Females of child bearing age with positive pregnancy test Neurodegenerative disease or other neurological disorder (dementia, Parkinson's disease, multiple sclerosis, seizure disorder, or brain tumours) History of neurosurgery within the last 30 days Acute brain injury within the last 30 days (ischemic/ haemorrhagic stroke, traumatic brain injury) Subject is anemic OR donated blood within the last 8 weeks OR has a hematological disorder that requires transfusions Subject has history of liver failure OR renal failure Study cohort: Advanced directives against resuscitation Traumatic cardiac arrest In hospital cardiac arrest Failure to attain ROSC + visible signs of death (livor mortis, rigor mortis) Control cohort: EKG changes: New ST-elevation consistent with myocardial infarction NSTEMI Hemodynamically unstable

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 Arrest cohort<br>adult patients (≥ 18 years of age) with non-traumatic out of hospital cardiac arrest | Procedure: blood draw<br>* Blood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72, 96, 120, 144 (10 draws total). Each draw would be approximately 20 mL of blood (but no less than 10 mL).<br>|
| Control cohort<br>matched control population will include hemodynamically stable patients who present to the ED with chest pain that is not of cardiac etiology (non-traumatic chief complaints). | Procedure: blood draw<br>* Blood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72, 96, 120, 144 (10 draws total). Each draw would be approximately 20 mL of blood (but no less than 10 mL).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital mortality | Higher blood biomarker levels will correlate with reduced rate of survival to hospital admission, survival to hospital discharge, and 6-month survival. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional neurological outcome at discharge | Higher blood biomarker levels will correlate with higher degree of neurological impairment as measured by Cerebral Performance Category. | 1 year | 
| Functional neurological outcome at 6 months after discharge | Higher blood biomarker levels will correlate with higher degree of neurological impairment as measured by Cerebral Performance Category. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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out-of-hospital cardiac arrest, neurological outcome, prognostication, cerebral performance category, hypoxic-ischemic brain injury, biomarkers