Microcirculatory Alteration and Biomarkers: New Approach for Early Assessment of Septic Multi-organ Dysfunction

Microcirculatory Alteration and Biomarkers: New Approach for Early Assessment of Septic Multi-organ Dysfunction

The aim of this study is to investigate associations between early structural cellular injury and microvascular alteration with progression of septic organ dysfunction according to total SOFA-Score (an ICU-scoring system - the Sequential Organ Failure Assessment Score). Patients will be monitored for renal (TIMP-2, IGFBP7), and intestinal biomarkers (plasma i-FABP) in conjunction with kidney and muscle vascular bed microvascular perfusion analysis assessed by contrast-enhanced ultrasonography (CEUS). In parallel, a comprehensive analysis of patients' immunological status will be conducted using an established, on-site immune monitoring panel.

The ultimate goal of this study is an early identification of septic patients developing multiorgan dysfunction which may facilitate a timely novel intervention in the future to improve outcome.

Inclusion Criteria:

Patients ≥18 years of age with severe sepsis and fulfill the following criteria at the admission to ICU:

• Peritonitis (abdominal infection) and performed source control (either surgically or interventionally)
• 2 or more criteria for systemic inflammatory response syndrome (temperature >38° or<36°; heart rate >90 beats per minute; respiratory rate >20 breaths per minute or paCO2 <32 mmHg; white blood cell count >12,000/mm3, <4000mm3 or >10% immature forms) and serum lactate level of 4mmol/l and more or refractory hypotension - mean arterial pressure <65mmHg or systolic blood pressure <90mmHg after fluid challenge of 1000ml or more /30min
• Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Written informed consent prior to any study procedures

Exclusion Criteria:

• Pre-existing renal-replacement therapy in the pre-operative course
• Pre-existing shock
• Acute coronary syndrome
• Active hemorrhage
• Trauma
• Known allergy to ultrasound contrast media
• Anemia with hemoglobin concentration < 7g/dl
• Patients not able to give written informed consent