Biomarkers, Genomics, Physiology in Critically Ill and ECMO Patients

Study Overview
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Brief Summary
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Patients in end-stage cardiac failure and/or respiratory failure may be started on a rescue therapy known as Extracorporeal Membrane Oxygenation (ECMO). One of the major clinical questions is how to manage the ventilator when patients are on ECMO therapy. Ventilator Induced Lung Injury (VILI) can result from aggressive ventilation of the lung during critical illness. VILI and lung injury such as Acute Respiratory Distress Syndrome (ARDS) can further increase the total body inflammation and stress, this is known as biotrauma. Biotrauma is one of the mechanisms that causes multi-organ failure in critically ill patients. One advantage of ECMO is the ability to greatly reduce the use of the ventilator and thus VILI by taking control of the patient's oxygenation and acid-base status. By minimizing VILI during ECMO we can reduce biotrauma and thus multi-organ failure. Since the optimal ventilator settings for ECMO patients are not known, we plan to study the impact of different ventilator settings during ECMO on patient's physiology and biomarkers of inflammation and injury.

Official Title
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Investigation of Biomarkers, Genomics, Physiology in Critically Ill and ECMO Patients

Conditions
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Acute Respiratory Distress Syndrome, Cardiac Failure, Extracorporeal Membrane Oxygenation Complication, Respiratory Failure, Renal Failure, Critical Illness, Pulmonary Disease

Intervention / Treatment
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* Device: Ventilator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patient currently on ECMO (Veno-Venous or Venous-Arterial or Venous-Arterial-Venous) Patient that is a potential ECMO candidate. Exclusion Criteria History of Lung or Cardiac Transplantation Patient is not committed to full support Treating clinician refusal, or unwillingness to commit to controlled ventilation for at least 4-6 hours (if patient is mechanically ventilated) Inability to get informed consent from the patient or surrogate.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Single group, intervention
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Driving Pressure Protocol<br>The patients ventilator driving pressure will be decreased (as tolerated by the patient) for 2 hours while on extracorporeal membrane oxygenation (ECMO) support. | Device: Ventilator<br>* The patient starts at a ventilator driving pressure of 10-15 cm of H2O as per guidelines for patients on ECMO with ARDS. The driving pressure is then decreased as tolerated for two hours to evaluate the effects on pulmonary, cardiac, and inflammatory biomarkers.<br>* Other names: Invasive mechanical ventilation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma IL-6 level from baseline to low driving pressure ventilation | IL-6 is a marker of systemic inflammation, previously used in studies of ECMO and ARDS. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma sRAGE from baseline to low driving pressure ventilation | sRAGE is a marker of systemic inflammation and acute lung injury, previously used in studies of ECMO and ARDS. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, ARDS, Ventilator induced Lung Injury, Heart Failure, Pulmonary Failure, Biomarkers