Delineating Between Pathophysiologic Phenotypes of Hypoxic Ischemic Brain Injury After Cardiac Arrest
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Oxygen extraction fraction
Study Overview
Brief Summary
The main outcome determinant following cardiac arrest is hypoxic ischemic brain injury. Management has involved increasing the delivery of oxygen to the brain. This logic assumes that oxygen transport from blood into the brain is normal. We have demonstrated that this assumption is not true. A large proportion of post-cardiac arrest patients demonstrate an inability to unload oxygen into the brain. The mechanisms explaining this observation are unclear. This project involves using a series of evaluations to differentiate post-cardiac arrest patients who exhibit normal and abnormal oxygen transport dynamics and also investigate the underlying mechanisms for abnormal oxygen transport.
Detailed Description
Purpose: To develop methods to differentiate between hypoxic ischemic brain injury patients exhibiting diffusion versus perfusion dependence. Secondarily, to investigate the underlying mechanisms responsible for diffusion limitation of oxygen delivery.
Hypotheses:
- Patients with PD will exhibit increases in O2EF when CBF is reduced during hypocapnic ventilation while patients with DL will exhibit a minimal change in O2EF, indicating the presence of impaired diffusive O2 transport.
- Serum brain biomarkers will be greater with DL vs. PD, indicating BBB permeability, glial and axonal injury.
- The lactate / pyruvate ratio will be increased in patients with DL vs. PD, indicating mitochondrial dysfunction.
- The clinical neurologic outcome will be worse in patients with DL compared to PD.
- There will be a decreased proportion of macrophages and associated circulating immune cells in the jugular venous bulb vs. the arterial circulation in DL patients.
Justification:
This research project aims to prospectively differentiate between pathophysiologic phenotypes of hypoxic ischemic brain injury (HIBI), delineate the underlying mechanisms and determine the associated clinical outcomes. In Canada, approximately 40,000 people per year suffer a cardiac arrest. HIBI, the resultant cerebral insult following cardiac arrest, is the predominant determinant of adverse outcome post-cardiac arrest with only 5-15% patients experiencing favorable neurological outcomes. The remainder of HIBI survivors may experience significant neuropsychiatric sequelae and with significant healthcare costs (~$160,000 per patient annually). Given these dismal results, significant opportunities exist to improve outcomes.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Greater than 19 years old post cardiac arrest with a Glasgow Coma Scale of 8 or less
- •Invasive monitoring implemented within 72 hours of cardiac arrest
- •Duration of cardiac arrest greater than 10 minutes.
Exclusion Criteria
- •Coagulopathy (INR > 1.5, PTT > 40, Platelets < 100x106 per microliter)
- •Current or anticipated use of anticoagulant or antiplatelet medication
- •Target temperature under 35oC; 4) history of severe TBI, intracranial hemorrhage or stroke.
Outcomes
Primary Outcomes
Oxygen extraction fraction
Time Frame: Over the first 72 hours
The fraction of oxygen which is extracted into the brain
Secondary Outcomes
- Venous to brain tissue oxygen tension gradient(Over the first 72 hours)
- Brain biomarker serum concentrations(Over the first 72 hours)
- Lactate to pyruvate ratio(Over the first 72 hours)
- Clinical outcome at 6 months(6 months post arrest)
Investigators
Myp Sekhon
Clinical Associate Professor
University of British Columbia