Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock

Study Overview
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Brief Summary
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To determine whether Levosimendan infusion in patients with cardiogenic shock and cardiorenal syndrome refractory to standard inotropic therapy, improves hemodynamics and renal function, whilst being safe.

Detailed Description
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Cardiogenic Shock or the state of systemic hypoxia albeit initially preserved intra-vascular volume and intact vascular function, is solely the result of insufficient cardiac output [1-2]. The ensuing centralization and redistribution of blood-volume, is induced by a stimulation of the renin-angiotensin system, as well as vasopressin and endogenous catecholamine liberation [2-3]. Precipitating Cardiogenic Shock has a direct effect on the kidney, also called the cardiorenal syndrome [4]. The overall consensus for the therapy of cardiogenic shock is the use of inotropes to increase cardiac output and reverse organ hypoxia [2], nevertheless their increase of myocardial and glomerular oxygen consumption make them a double edged sword to use in cardiogenic shock and more prominently in cardiogenic shock coupled with pronounced cardiorenal syndrome. Levosimendan is an inotropic agent that was developed for the treatment of severely decompensated heart failure. It exerts its inotropic effects primarily through sensitizing Troponin C to calcium and thereby increasing contraction of cardiac myofilaments during systole [5]. Unlike other inotropic agents, Levosimendan acts independently of the beta adrenergic receptor [5]. Additionally, the effect of Levosimendan could be beneficial for the kidneys function by decreasing pre-glomerular arteriolar vasotonus whilst keeping post-glomerular arteriolar vasotonus constant [6]. In light of the scarce but promising literature the question arises if Levosimendan can safely ameliorate cardiac and renal function concomitantly in patients presenting the combination of cardiogenic shock and cardiorenal syndrome.

Official Title
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Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock

Conditions
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Cardiogenic Shock, Cardiorenal Syndrome, Acute Kidney Failure

Intervention / Treatment
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* Drug: Levosimendan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Levosimendan Cardiogenic Shock Continuous monitoring of cardiac output at the start of and during treatment with Levosimendan Exclusion Criteria: Extracorporal hemodynamic support or an implanted ventricular assist device Previous therapy with Levosimendan during the index hospitalization Refusal of participation in the study

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Levosimendan Treated Group<br>All patients consecutively admitted to the medical ICU of the University Hospital Zurich aged over 18 years, with an underlying cardiogenic shock, receiving Levosimendan. | Drug: Levosimendan<br>* Levosimendan was administered according to a standardized treatment protocol. A total dose of 12.5mg or 25mg (corresponding to one or two ampoules) was given at an infusion rate of 0.05 μg/kg/min to 0.2μg/kg/min with or without a loading dose (6 μg/kg or 3 μg/kg over 10 minutes). The decision about total dose, infusion rate and loading dose was at the discretion of the treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiac Index | Temporal development of Cardiac Index post Levosimendan Infusion up until 120 hours | Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion | 
| Change in Cardiac Preload Pressures | Temporal development of Wedge Pressure/ Central Venous Pressure post Levosimendan Infusion up until 120 hours | Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion | 
| Change in Mean Arterial Pressure | Temporal development of Mean Arterial Pressure post Levosimendan Infusion up until 120 hours | Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion | 
| Change in Vasoactive/ Inotropic Dosage | Temporal development of Norepinephrine/ Dobuatmine Dosage post Levosimendan Infusion up until 120 hours | Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion | 
| Change in Renal Function | Temporal development of eGFR (Creatinin estimated) post Levosimendan Infusion up until 120 hours | Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion | 
| Change in Fluid Balance | Temporal development of Fluid Balance post Levosimendan Infusion up until 120 hours | Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levosimendan, Inotropic Agent