Impact of Adrenoreceptor Expressions on Inflammatory Pattern in Refractory Cardiogenic Shock Under VA ECMO

Study Overview
=================
Brief Summary
-----------------
Refractory cardiogenic shock is characterized by a decreased in cardiac output with hypo-responsiveness to increasing doses of catecholamines resulting in a profound tissular ischemia. VAECMO, by restoring a circulatory flow, could be associated to a major reperfusion syndrome which may lead some patients to multiple organ failures and death. Pathophysiology of this syndrome includes 1/an hyper-adrenergic state secondary to the over activation of the sympathetic system and 2/ a major release of pro-inflammatory cytokines. As adrenoreceptors are also exhibited on immunes cells, the pro-inflammatory state might be enhanced by the over-activation of the sympathetic system.

Detailed Description
-----------------
NB : A repartition according to other ongoing study (HYPOECMO NCTNCT02754193) is planned

Official Title
-----------------
Impact of Adrenoreceptor Expressions on Inflammatory Pattern in Refractory Cardiogenic Shock Patients Treated by Veno-arterial Extra-Corporeal Membrane Oxygenation

Conditions
-----------------
Shock, Cardiogenic, Extra-Corporeal-Life-Support ( ECLS), Autonomic Nervous System Diseases, Inflammation

Intervention / Treatment
-----------------
* Diagnostic Test: Biological


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients in ICU Refractory cardiogenic shock Cardiogenic shock: Systolic Arterial Pressure <90mmHg, or Mean Arterial Pressure <65mmHg, adequate volemia, peripheral hypoperfusion symptoms, cardiac index < 2.2 l/min/m2) Refractory state: hypo responsiveness to norepinephrine AND/OR persisting profound hypo perfusion clinical symptoms despite optimal resuscitation needing an Extra-Corporeal-Life-Support informed consent from relatives or patient Affiliation to a social security regimen Preliminary medical examination Exclusion Criteria: Patients under ECLS for a/an : Cardiotoxic poisoning Human immunodeficient Virus or Viral hepatitis C Patient < 18 yo Pregnancy Patient under protective supervision

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Refractory cardiogenic shock patients under ECLS. Assessment at ECLS start, day 3 and Day ECLS weaning for various biological variables
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Refractory cardiogenic shock under ECLS<br> | Diagnostic Test: Biological<br>* We will assess in all patients under ECLS for the treatment of a cardiogenic shock at day 0 (ECLS initiation) day 3 and day ECLS weaning : Biological assessment: Adrenoreceptors α1, α2, β1, β2, β3 on monocytes and lymphocytes T helper by flow cytometry Lymphocytes Th1/Th2 pattern by flow cytometry Cytokines on plasma : Interleukin (IL) 4, IL 12, TNF α, INF γ , IL1, IL6, IL10 Clinical assessment: Hemodynamic parameters Cumulated doses of catecholamines Cardiac output variation measured by echocardiography during a standardized weaning procedure of ECLS at a constant mean arterial pressure (only on day 3 and Day ECLS weaning)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cytokines (plasma TNF α, INF γ, IL4, IL 12, IL1 IL 6 IL 10) | Exposition variable will be the density of α1, α2, β1, β2, β3-adrenoreceptors on immune cells (monocytes and lymphocytes T helper) | day 0 (ECLS initiation), day 3, day ECLS weaning | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemodynamic parameters | Arterial pressures | day 0 (ECLS initiation), day 3, day ECLS weaning | 
| Change in hemodynamic parameters | heart rate | day 0 (ECLS initiation), day 3, day ECLS weaning | 
| Change in hemodynamic parameters | cumulated doses of catecholamines | day 0 (ECLS initiation), day 3, day ECLS weaning | 
| Cardiac output variation during a weaning ECLS procedure | At a constant mean arterial pressure (65-75 mmHg), measurement by echocardiography of cardiac output at 2 times: baseline (3L/min of ECLS flow) after 45 min at weaning output (1.5 L/min of ECLS flow) Variation of norepinephrine doses will be also recorded | day 3, day ECLS weaning | 
| Mortality |  | 28 days and 90 days | 
| Change in TH1 and TH2 pattern | Assessment in CD3/CD4 + cells of INF γ; IL12 (TH1) and IL4 (TH2) | day 0 (ECLS initation), day 3, day ECLS weaning | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cardiogenic shock, Extra-Corporeal-Life-Support (ECLS), inflammation, adrenergic system