Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock

Study Overview
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Brief Summary
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The aim of this study is to investigate the effects milrinon and levosimandan on n heart function in septic cardiomyopathy and how norepinephrine affects the left and right ventricular function in patients with septick shock using pulmonary artery catheter, conventional and strain echocardiography.

Detailed Description
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This is a prospective study where 30 patients with septic chock during the care in ICU, will be included. Patients with a history of previous heart disease are excluded from the study. Each patient is in need of norepinephrine infusion and on mechanical ventilation. Initially the mean arterial pressure (MAP) is randomly changed from 60 to 75 and then to 90 mmHg. Hemodynamic variables as blood pressure, cardiac output, pulmonary artery occlusion pressure (PAOP) will be registerd at each MAP-level, arterial line and pulmonary artery catheter (PAC) and the cardiac function will be assessed with conventional and strain echocardiography. Then, if the echocardiogram shows impaired LV-function will the patient be randomized to receive either Milrinone or Levosimendan. Hemodynamic variables as blood pressure, cardiac output, pulmonary artery occlusion pressure (PAOP) will be registered again, as well the cardiac function with conventional and strain echocardiography. Echocardiograms will be analysed for the determination of LV an RV strain. Potential differences between different levels of blood pressure as well as effects of Milrinone or Levosimendan on hemodynamic and echocardiographyc variables will be analysed.

Official Title
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Potential Differences Between Levosimendan and Milrinone on Myocardial and Hemodynamic Variables in Patients With Septic Cardiomyopathy. Effects of Norepinephrine on Right Ventricular Function in Patient With Septic Shock.

Conditions
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Septic Shock, Cardiomyopathy

Intervention / Treatment
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* Drug: Norepinephrine
* Drug: Milrinone
* Drug: Levosimendan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Septic shock. All patients will be resuscitated with fluids before the inclusion. Need of Norepinephrine infusion. Myocardial dysfunction in echocardiogram, either LVEF < 50% or Global Left Ventricular Systolic strain over -15%. Exclusion Criteria: History of previous heart disease or pulmonary hypertension. Age < 18 years. Cardiac arrhythmia.

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Norepinephrine<br>Doser | Drug: Norepinephrine<br>* Norepinephrine will be given to the patient due to septic shock. After the inclusion we will change the dose of Norepinephrine to achieve 3 different MAP-levels, 60 mmHg, 75 mmHg and 90 mmHg.<br>|
| Active Comparator: Milrinone<br>Doser | Drug: Milrinone<br>* Corotrope will be given and after 30 minutes of treatment the cardiac function will be assessed with echocardiography and systemic hemodynamics.<br>* Other names: Corotrope;|
| Active Comparator: Levosimendan<br>Doser | Drug: Levosimendan<br>* Levosimendan will be given and after 30 minutes of treatment the cardiac function will be assessed with echocardiography and systemic hemodynamics.<br>* Other names: Simdax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in LV systolic strain | Changes in LV systolic function (global strain) will be assessed by 2D speckle tracking echocardiography | 1.5 hours | 
| Changes in RV systolic strain | Changes in RV systolic function (RV free wall strain) will be assessed by 2D speckle tracking echocardiography | 1.5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levosimendan, Milrinone, Myocardial strain, Septic cardiomyopathy, Norepinephrine