Sepsis is a life-threatening clinical syndrome that is caused by an overwhelming reaction of the immune system to a severe bacterial infection. The subsequent systemic inflammation results in a complex pathophysiology that affects the entire organism, compromising vascular integrity and leading to septic shock, multiple organ failure and death. The early treatment with antibiotics as well as hemodynamic support are a key elements of current sepsis management on ICU. However, despite considerable improvement in hospital hygiene, the progress in the development of antibacterial agents and various immunomodulatory therapy attempts, sepsis incidence has doubled in the past 10 years and the mortality rate still remains high at approx. 30%. Once the patient developes a septic shock the mortality rate coverges to 50-80%.
Sepsis begins with a local, mostly bacterial, infection. The resulting inflammation is initiated by cells of the innate immune system, mainly macrophages and dendritic cells, that are able to recognize pathogen-associated molecular patterns. The soluble inflammatory mediators released by activated leukocytes or injured tissue cells cause a loss in endothelial barrier and local vasodilation and attract further phagocytes like neutrophils, which in turn recruit additional leukocytes and lymphocytes into the inflammed tissue. Since the vascular endothelium is the major stage of these events, prolonged and excessive systemic inflammation results in microvascular injuries and finally to the loss of endothelial integrity (vascular leakage). The dilation and disruption of the vascular endothelium is responsible for organ dysfunctions, tissue hypoxia and septic shock.