Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock

Study Overview
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Brief Summary
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The efficacy and tolerability of norepinephrine and epinephrine in cardiogenic shock after reperfused myocardial infarction will be compared, by following cardiac index evolution as main criteria. The study is a pilot pathophysiological study, randomized, double blind and multicenter.

Detailed Description
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Cardiogenic shock secondary to myocardial infarction is a frequent pathology in reanimation and is associated with high mortality (50%). Hemodynamic management and notably the choice of vasopressor in cardiogenic shock states secondary to myocardial infarction (cardiac index < 2.2 l/min/m-2) is not codified. There are two opposite views: a) the first is based on the fact that an hypotensive patient with low cardiac output is primarily in need of an inotropic agent and that, consequently, epinephrine is the molecule of choice (inotropic and vasoconstrictor); b) the second is based on the fact that hypotension also reflects a certain degree of vascular failure and vascular vasoplegia and therefore norepinephrine is the molecule of choice along with, if needed, the eventual addition of dobutamine in order to separately titrate vasoconstriction and inotropism. Study hypotheses: epinephrine could facilitate myocardial function by providing the latter with its preferred substrate (lactate) and thus induce a higher cardiac index along with increased energy expenditure. Norepinephrine is the therapy of choice of hypotensive states; nevertheless its lack of inotropic effect could theoretically exacerbate myocardial failure. Thus, the aim of the study is to compared the efficiency and the tolerability of norepinephrine and epinephrine in cardiogenic shock after reperfused myocardial infarction.

Official Title
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Optimizing the Use of Vasopressor After Coronary Reperfusion in Cardiogenic Shock Secondary to Myocardial Infarction. Pathophysiological Study Comparing the Efficacy and Cardio-circulatory Tolerability of Epinephrine and Norepinephrine

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Drug: epinephrine perfusion
* Drug: norepinephrine perfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: man or woman older than 18 years cardiogenic shock due to myocardial infarction treated by angioplasty SAP < 90 MM Hg or MAP < 65 mm Hg without vasopressor or vasopressor necessity sign of tissue hypoperfusion cardiac index < 2.2 l/mn/m2 in the absence of vasopressive or inotropic therapy pulmonary artery occlusion pressure > 15 mmHg or echocardiographic evidence of high pressure (mitral profile) exclusion of covert hypovolemia : Delta PP if feasible should be > 13% (patient adapted to the ventilator and sinus rhythm) and /or no response to passive leg raising ejection fraction < 40% in ultrasound without inotrope support. This criteria will not be taken into account in instances of treatment with dopamine, norepinephrine, epinephrine, dobutamine or milrinone. Exclusion Criteria: shock of other origin immediate indications for mechanical assistance device minor aged patients patients for whom written consent - by patient or family - has not been obtained. Given the seriousness of the medical situation at the time of inclusion, patient consent will be difficult if not impossible to obtain. The inclusion will only be possible after information is provided and consent is obtained from a family member. As soon as possible, protocol information will be issued to the patient in order to obtain consent for continuance. cardiac arrest with early signs of cerebral anoxia. septic, toxic and obstructive cardiomyopathy arrhythmogenic cardiomyopathy patient with coronary insufficiency patient with ventricular rhythm disorders patient treated with a medicine listed in contre indication patient without social assurance patient major under legal protection or safeguard justice

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: epinephrine<br> | Drug: epinephrine perfusion<br>* perfusion of commercial epinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg<br>* Other names: catecholamine;|
| Active Comparator: norepinephrine<br> | Drug: norepinephrine perfusion<br>* perfusion of commercial norepinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg<br>* Other names: catecholamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compared effects of investigated drugs on cardiac index | effectiveness of the treatment assessed by the evolution of cardiac index | H0; H2, H4, H6, H12, H24, H48 and H72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pro/anti-inflammatory cytokines | Compared effects of investigated drugs on pro/anti-inflammatory cytokines | H0, H24, H48 and H72 | 
| BNP | Compared effects of investigated drugs on BNP | H0, H24, H48 and H72 | 
| Troponin | Compared effects of investigated drugs on Troponin | H0, H24, H48 and H72 | 
| catecholamine doses | Compared effects of investigated drugs on the catecholamine doses | H0, H24, H48 and H72 | 
| organ failure (SOFA Score) | Compared effects of investigated drugs on the organ failure | H0, H24, H48 and H72 | 
| Lactate clearance | Compared effects of investigated drugs on the Lactate clearance | H0, H2, H6, H12, H24 and H48 | 
| heart rate | Compared effects of investigated drugs on heart rate and the incidence of arrhythmia | H0, H2, H4, H6, H12, H24, H48 and H72 | 
| cardiac power index | Compared effects of investigated drugs on cardiac power | H0, H2, H4, H6, H12, H24, H48 and H72. | 
| SVO2 | Compared effects of investigated drugs on the SVO2 | H0, H2, H4, H6, H12, H24, H48 and H72. | 
| cardiac double product | Compared effects of investigated drugs on the cardiac double product | H0, H2, H4, H6, H12, H24, H48 and H72. | 
| refractory cardiogenic shock | compared effects of the investigated drugs on the occurrence of refractory cardiogenic shock | H0, H2, H4, H6, H12, H24, H48 and H72. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myocardial infarction, epinephrine, norepinephrine, cardiac output