Microcirculatory Oxygen Uptake in Sepsis

Study Overview
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Brief Summary
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Forearm vasoocclusive testing (VOT) will be performed with laser-doppler spectrophotometry system in septic patients on ICU. Microcirculatory oxygen uptake will be checked for prognostic value and for associations with tissue hypoxia markers and high central venus saturations.

Detailed Description
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Sepsis remains a common entity in critical care patients with remarkable mortality. Microcirculatory dysfunction plays a pivotal role in the pathophysiology of sepsis and organ dysfunction. The main causal mechanisms are vasoactive substances such as nitric oxide and endothelin, destroyed endothelial surfaces and microvascular occlusion by activated coagulation and leucocytes. Furthermore there is some knowledge from vasooclussive testing (VOT) based on near-infrared spectroscopy (NIRS) and assessing the proportion of perfused vessels determined with orthogonal polarization spectral and sidestream darkfield imaging techniques (SDF) that impaired microcirculation is associated with organ dysfunction and increased mortality. Despite these well-recognised evidence previous trails proving therapy guidance with microcirculatory parameters failed in demonstrating optimised outcome . Recent guidelines still recommend fluid therapy based on central venous pressure, mean arterial pressure, urine output and or blood lactate concentration. But especially the parameter central venous oxygen saturation (ScvO2) seems to be not unproblematic. Retrospective data analysis found higher mortality rates if ScvO2 is elevated. In the present study patients with sepsis, severe sepsis and septic shock will be evaluated on day 1 and day 4 and a follow up will be performed on day 180. Additional to clinical parameters of organ function, infection markers, global parameters of tissue hypoxia will be captured by measurements of adenosine and whose metabolites. Macrocirculatory cardiovascular function delivered by transpulmonary thermodilution technique will be assessed and local tissue perfusion and oxygen uptake will be measured with a transcutaneous laser-doppler spectrophotometry system in VOT. The aim of this study is to check: Is microcirculatory oxygen uptake a prognostic value in sepsis? Is it correlated with biomarkers of hypoxia? Are high levels of ScvO2 caused by microcirculatory impairments or by hyperdynamic macrocirculation?

Official Title
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Microcirculatory Oxygen Uptake in Sepsis, Severe Sepsis and Septic Shock

Conditions
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Sepsis, Severe Sepsis, Septic Shock

Intervention / Treatment
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* Other: Vasoocclusive testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Criteria according to the SSC for sepsis, severe sepsis and septic shock Admission to the ICU within 24 hours Exclusion Criteria: Pregnancy Cardiopulmonary resuscitation within the last 5 days

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 |
| --- | --- |
| Vasoocclusive testing in sepsis<br>Septic patients defined according to the Surviving Sepsis Campaign (SSC) | Other: Vasoocclusive testing<br>* Forearm vasoocclusive testing with a laser-doppler spectrophotometry system, transpulmonary thermodilution and blood sampling;<br>|
| Vasoocclusive testing in severe sepsis<br>Severe septic patients defined according to the Surviving Sepsis Campaign (SSC) | Other: Vasoocclusive testing<br>* Forearm vasoocclusive testing with a laser-doppler spectrophotometry system, transpulmonary thermodilution and blood sampling;<br>|
| Vasoocclusive testing in sepsic shock<br>Septic shock patients defined according to the Surviving Sepsis Campaign (SSC) | Other: Vasoocclusive testing<br>* Forearm vasoocclusive testing with a laser-doppler spectrophotometry system, transpulmonary thermodilution and blood sampling;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | ICU-Mortality, 60-days-mortlity, 180-days-mortality will be recorded and correlated with baseline and postischemic microcirculatory oxygen delivery and uptake. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Connection between ScvO2 and microcirculatory oxygen uptake | The investigators will prove, if high values of central venous saturation (>75%) are associated with impaired tissue oxygen uptake. | Day 1 and day 4 | 
| Connection between adenosine-metabolites and microcirculatory oxygen uptake | The investigators will prove, if high values of the adenosine-metabolite hypoxanthine (ng/ml) in plasma are associated with impaired tissue oxygen uptake. | Day 1 and day 4 | 
| Physical condition | Physical status at 180 days (Rankin-Scale) will be recorded and correlated with baseline and postischemic microcirculatory oxygen delivery and uptake. | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microcirculation, oxygen uptake, hypoxia, adenosine, central venous saturation, hypoxanthine, laserdoppler