Sepsis—Current Aspects of Pathophysiology and Implications for Diagnosis and Management

Abstract

Sepsis is characterized by disrupted inflammatory homeostasis due to infection. While a localized and controlled inflammatory reaction helps to eliminate and control infection, a dysregulated host response triggers multiple organ failure determining course and prognosis. Consequent surgical source control paralleled by adequate and early antibiotic therapy remains the cornerstone of care. Nevertheless, mortality remains as high as 50–60% for severe sepsis and septic shock. As the molecular mechanisms are becoming increasingly better defined, interventions aiming to interfere with the host response to infection have been undertaken, largely with disappointing results. Thus, many evidence-based recommendations suggest waiving of resource-consuming interventions, such as supplementation of antithrombin or immunoglobulins. Nevertheless, several seminal studies have indicated that meticulous supportive care according to pathophysiological principles, most notably early goal-directed therapy, low-dose hydrocortisone and activated protein C, can disrupt dysfunctional cascades favorably influencing the course of the disease. In parallel, there is increasing evidence from national and international surveys that therapy of severe sepsis on ICUs worldwide is generally in poor compliance with current guidelines, while personal perception of the physicians in charge would suggest high rates of adherence to evidence-based recommendations. Thus, strategies of change management, such as implementation of ‘sepsis bundles’, are warranted to achieve better standards of care toward the aim of the “surviving sepsis campaign”, i.e. a reduction of mortality rates by 25% within the next years.