Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response

Abstract

To describe the pathogenesis and emphasize prognosis of systemic inflammatory response during severe infection. Host immune response enables to confine and clear microorganisms. Sometimes for current unknown reason depending on host (genetic susceptibilities and comorbidities) and pathogen (load and virulence) factors, this reaction is accompanied by a widespread reaction characterized by a first pro-inflammatory response (called at the bedside, systemic inflammatory response syndrome) and a following 'immune paralysis' (compensatory anti-inflammatory response syndrome) responsible for secondary infections. There are three recognized stages of severe host response to pathogen with progressively increased mortality rates: sepsis, severe sepsis, and septic shock. This excessive reaction induces microthrombi formation, capillary obstruction by red blood cells losing their deformability, microcirculatory alterations, tissue edema by capillary leak, and neutrophil recruitment leading to multiple tissue damages, organ failures (multiple organ dysfunction syndrome) and finally to death. Despite the early detection, the use of modern antibiotics and new resuscitation therapies, sepsis remains a leading cause of death in critically ill patients. Sepsis is viewed as an excessive host response to pathogen inducing a complex network of molecular cascades leading to tissue damages, organ failures, and death.