Immunoinflammatory Response in Post Cardiac Arrest Syndrome (PCAS)

Study Overview
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Brief Summary
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This is a prospective, observational study to investigate molecular mechanisms mediating the systemic inflammatory process, and their impact on brain injury, survival, and functional outcomes after cardiac arrest. Investigators have shown that cardiac arrest induces changes in the numbers and properties of circulating immune cells, shifting the balance towards a pro-inflammatory phenotype and there is increased interest in the inflammatory pathways and the signaling mechanisms through which they are modulated. Participants will undergo blood sampling during 7 days following cardiac arrest, and analyses performed. Patient characteristics, clinical circumstances, and outcomes will be recorded and their associations with these inflammatory pathways characterized.

Detailed Description
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Preliminary evidence indicates that inter-individual variables such as immune cell activity and the production of pro-inflammatory factors may differentiate patients with the highest risk of poor neurological outcome, and may reveal novel therapeutic approaches based on promoting molecular pathways of inflammation-resolution and recovery to reduce the severity of HIE. Comparative analysis showed that cardiac arrest survivors have more CD73+ lymphocytes compared to non-survivors. CD73 is the key enzyme in the generation of anti-inflammatory and immunosuppressive adenosine. We have also identified novel populations of neutrophils (CD14posCD16low and DEspR+) that had amplified response to inflammatory stimuli. The investigators hypothesize that individual variability in the expression and signaling profiles of white blood cells (lymphocytes, neutrophils, monocytes and macrophages) following resuscitation affects inflammation and is independently associated with neurological outcome. To test this hypothesis, investigators will determine levels of various immune cell populations at different time points in peripheral blood of patients. Characterization of blood circulating factors, clinical phenotypes, and neurological outcomes after cardiac arrest is a second aim of this project, with a focus on understanding the heterogeneity of cellular and humoral immune responses and how they relate to different clinical phenotypes of post-resuscitation syndrome.

Official Title
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Immunoinflammatory Response in Post Cardiac Arrest Syndrome (PCAS)

Conditions
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Cardiac Arrest, Inflammation, Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older Admitted to the intensive care unit after cardiac arrest episode Unresponsive after resuscitation Exclusion Criteria: Moribund Informed consent cannot be obtained within 24 hours of resuscitation Hemoglobin less than 7.0 g/dL or requiring a transfusion

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlations between inflammatory markers and clinical outcomes | Correlations between inflammatory markers and clinical outcomes | 14 days | 
| Correlations between inflammatory markers and biomarkers of neurological and cardiac injury | Correlations between inflammatory markers and biomarkers of neurological and cardiac injury | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of post-resuscitation inflammatory mechanisms and their regulators | Characterization of post-resuscitation inflammatory mechanisms and their regulators | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac arrest, inflammation, immune, neuregulin, lymphocyte, neutrophil