Microcirculation Guided Therapy Versus Standard Treatment of Severe Sepsis

Study Overview
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Brief Summary
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The purpose of this study is to asses the recovery of organ failure between two resuscitation protocols in severe sepsis: standard, pressure guided therapy versus a microcirculation guided therapy

Detailed Description
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Despite continued improvements in medical therapy, mortality from septic shock has remained between 30% and 70% for the past three decades with only a slight decrease in mortality rate. Standard treatment of septic shock is fluid resuscitation, followed by agents with vasopressor activity to correct hypotension in septic shock. The question rises whether vasopressors should be the first line of action in septic shock Opening and recruiting the microcirculation are expected to improve regional organ function and tissue distress in severe sepsis. Beside fluid resuscitation, vasodilatation, in this respect, enhances microcirculatory flow while vasoconstriction causes a reduction in microcirculatory flow. On the other hand, a minimal perfusion pressure should be present. Our aim is to asses the effects of two resuscitation protocols in severe sepsis: the standard treatment using predefined pressure goals versus a microcirculation guided therapy.

Conditions
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Severe Sepsis, Microcirculation

Intervention / Treatment
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* Drug: Dopamine
* Drug: dobutamine
* Drug: enoximone
* Drug: nitroglycerine
* Drug: noradrenaline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 years or older admission to the intensive care unit with severe sepsis, defined in according with a modification of the American College of Chest Physician/SCCM guidelines criteria intention to provide full intensive care treatment for at least 72 hours and written informed consent to be obtained from patient or next of kin. Exclusion Criteria: haematologic malignancy metastatic malignancy AIDS with CD4 < 50 cells/mm3 liver cirrhosis Child Pugh B & C pregnancy post resuscitation with GCS < 8 of 15 and treatment with induced hypothermia

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Dopamine|nan|
|Drug: dobutamine|nan|
|Drug: enoximone|nan|
|Drug: nitroglycerine|nan|
|Drug: noradrenaline|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in SOFA (Sequential Organ Failure Assessment) score during the first 72 hours of treatment for severe sepsis |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity, decrease and duration of organ failure over the complete ICU stay |  | complete icu stay | 
| Duration of organ support |  | during ICU treatment | 
| ICU and hospital length of stay |  | hospital stay | 
| ICU and hospital mortality |  | hospital stay | 
| Inflammatory response measured by IL-6/IL-10 |  | 72 hours | 
| Plasma concentration of asymmetric dimethyl arginine (ADMA |  | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, severe sepsis, microcirculation, Orthogonal polarisation spectral