Advances in pathogenesis and management of sepsis

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Abstract
The rationale for therapeutic targets in sepsis has arisen from the concept of pathogenesis. This review focuses on recent advances in pathogenesis of sepsis that can aid in management of sepsis patients. Cellular survival in sepsis is related to the magnitude of the stimulus, the stage of the cell cycle and the type of microbe. While phenotypic modification of the endothelium (procoagulant and proadhesive properties, increased endothelial permeability, endothelial apoptosis and changes in vasomotor properties) leads to vasoplegia as a direct correlate to septic shock mortality, phenotypic changes in the epithelium cause activation of the virulence of the opportunistic pathogens and loss of mucosal barrier function, the latter causing a vicious circle in severe sepsis. Early identification of sepsis with protocolized screening, triggering evidence-based protocolized care, is anticipated to reduce sepsis morbidity and mortality. Current treatment of sepsis includes early antibiotic therapy, early aggressive goal-directed resuscitation targeting tissue hypoperfusion, steroids (for refractory shock), activated protein C (for high risk of death) and maintaining support of organ systems. A better understanding of pathogenesis of sepsis has led to specific proven management tools that are likely to improve clinical outcome once incorporated into protocolized care.