Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock

Study Overview
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Brief Summary
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To investigate changes in the concentration of glucose, lactate, pyruvate and glycerol in the extracellular fluid of the skeletal muscle following levosimendan administration in patients with septic shock.

Detailed Description
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The study was designed as a prospective, double-blind, controlled, clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 20 septic shock patients were randomized to receive either levosimendan 0.2 μg/kg/min, or dobutamine 5 μg/kg/min. Interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were obtained by using muscle microdialysis. All measurements, including data from right heart catheterization were obtained at baseline and every 6 hours for the following 72 hours after randomization.

Official Title
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Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock: A Randomised Controlled Study

Conditions
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Septic Shock

Intervention / Treatment
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* Device: Microdialysis Probe (Muscle microdialysis)
* Drug: Dobutamine
* Drug: Levosimendan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who fulfilled the criteria of septic shock that required norepinephrine (NE) to maintain a mean arterial pressure (MAP) of at least 65 mm Hg despite appropriate volume resuscitation (pulmonary arterial occlusion pressure [PAOP] = 12 to 18 mm Hg and central venous pressure [CVP] = 8 to 12 mm Hg) Exclusion Criteria: pregnancy, uncontrolled hemorrhage, terminal heart failure, significant valvular heart disease, documented or suspected acute coronary syndrome, and a limitation on the use of inotropes: left ventricle outflow obstruction, systolic anterior motion of the mitral valve.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 90 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: levosimendan 0.2 μg/kg/min<br>Treatment with levosimendan 0.2 μg/kg/min 24h (without bolus). Muscle microdialysis was performed using a microdialysis probe inserted into the quadriceps femoris muscle. | Device: Microdialysis Probe (Muscle microdialysis)<br>* Interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were determined at baseline and then every six hours for the following 72 hours after randomization. During the study period, conventional treatment was continued as per usual practice. Fluid challenges were performed, and repeated as necessary, to maintain central venous pressure (CVP) ≥8 and pulmonary arterial occlusion pressure (PAOP) ≥12 mmHg. Norepinephrine was titrated to maintain mean arterial pressure (MAP) ≥65 mmHg. Packed red blood cells were transfused when Hemoglobin (Hb) concentrations decreased below 7 g/dL, or if the patient exhibited clinical signs of inadequate systemic oxygen supply.<br>Drug: Levosimendan<br>* Levosimendan (0.2 μg/kg/min) will be used as indicated<br>* Other names: SIMDAX;|
| Active Comparator: dobutamine 5 μg/kg/min<br>Treatment with dobutamine 5 μg/kg/min. Dobutamine were administered during all the 72 hours study period. Muscle microdialysis was performed using a microdialysis probe inserted into the quadriceps femoris muscle. | Device: Microdialysis Probe (Muscle microdialysis)<br>* Interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were determined at baseline and then every six hours for the following 72 hours after randomization. During the study period, conventional treatment was continued as per usual practice. Fluid challenges were performed, and repeated as necessary, to maintain central venous pressure (CVP) ≥8 and pulmonary arterial occlusion pressure (PAOP) ≥12 mmHg. Norepinephrine was titrated to maintain mean arterial pressure (MAP) ≥65 mmHg. Packed red blood cells were transfused when Hemoglobin (Hb) concentrations decreased below 7 g/dL, or if the patient exhibited clinical signs of inadequate systemic oxygen supply.<br>Drug: Dobutamine<br>* Dobutamine (5 μg/kg/min) will be used as indicated<br>* Other names: DOBUTREX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in the concentration of glucose(mmol/l) in the extracellular fluid of the skeletal muscle |  | At baseline and then every six hours for the following 72 hours after randomization. | 
| changes in the concentration of lactate(mmol/l) in the extracellular fluid of the skeletal muscle |  | At baseline and then every six hours for the following 72 hours after randomization. | 
| changes in the concentration of pyruvate (µmol/l) in the extracellular fluid of the skeletal muscle |  | At baseline and then every six hours for the following 72 hours after randomization. | 
| changes in the concentration of glycerol (µmol/l) in the extracellular fluid of the skeletal muscle |  | At baseline and then every six hours for the following 72 hours after randomization. |