Esmolol Effects on Heart and Inflammation in Septic Shock

Study Overview
=================
Brief Summary
-----------------
Beta adrenergic system, over-activated in septic shock patients, is a key modulator of the inflammatory response. Experimental works demonstrated that Esmolol, an highly selective beta-1 blocker, reduces heart rate and regulates the inflammatory response. A recent mono centric, double blind, randomized clinical work in septic shock patients has shown that Esmolol administration is safe and reduces effectively heart rate. However there are only sparse data on 1) regional and micro-circulation, 2) inflammation modulation in human resuscitated septic shock patients treated by esmolol.

Official Title
-----------------
Anti-inflammatory and Cardiac Effects of Esmolol in Septic Shock. ESMOSEPSIS Study

Conditions
-----------------
Septic Shock

Intervention / Treatment
-----------------
* Drug: Esmolol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: septic shock patients following the definition of the Surviving Sepsis Campaign femoral and central venous catheters for thermodilution monitoring fluid optimization with a cardiac index > 3 l/min/m2 Heart Rate >100 /min Exclusion Criteria: Cardiogenic shock Bradycardia History of Severe Asthma Indications against esmolol

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESMOLOL<br>Resuscitated, hyperkinetic septic shock patients are treated with esmolol in order to reduce heart rate of 20% during 6 hours. During the intervention period, multimodal macro and micro hemodynamic data are recorded. | Drug: Esmolol<br>* After, at least six hours of hemodynamic optimization, patients with an hyper dynamic shock received a conventional management with a continuous infusion of Esmolol titrated to gain a 20% reduction in heart rate. This infusion is maintained for six hours.<br>* Other names: Brevibloc;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic effects of Esmolol in septic shock patients (Value of cardiac index l/min/m2) | Compare, in septic shock patients, the mean cardiac index before and after administration of Esmolol. | Before administration (H0) and each hour (H1-H2-H3-H4-H5-H6) during the whole administration period and one hour after Esmolol cessation (H7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects on vasopressor requirement (amount of norepinephrine infused in microgram/kg) during Esmolol administration |  | Record of each change in vasopressor dosage to maintain a mean arterial pressure at 70 mmHg during the whole Esmolol administration period (H0 to H6) and one hour after esmolol cessation (H7) | 
| Microcirculatory and regional circulation effects of Esmolol in septic shock patient | NIRS (near-infrared spectroscopy) SDF (Sidestream Dark Field imaging) / Limon (non-invasive measurement of liver function and splanchnic perfusion monitoring) are used to asses microcirculatory and regional circulation effects | Before (H0), 6 hours after Esmolol introduction (H6) and 1 hour after esmolol cessation (H7) | 
| Changes in the Cytokine pattern(pro and anti inflammatory cytokines assay) induced by Esmolol administration in septic shock patients |  | Before administration of Esmolol (H0) and 6 hours after introduction of Esmolol (H6) | 
| Description of the cardiac function during Esmolol Administration in septic shock patients | Use of Echocardiography to assess ventricular function | Before administration (H0), at 4 hours, 6 hours after introduction and 1 hours after esmolol cessation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Septic Shock, Hemodynamic, Inflammatory status, Beta adrenergic modulation, Esmolol