Sepsis, severe sepsis, and septic shock represent a spectrum of increasingly severe diseases that result from serious infection and the body’s response to microbiologic invasion. Population data suggest that 750,000 cases of severe sepsis occur in the United States annually; this illness is responsible for as many deaths as acute myocardial infarction (215,000, or 9.3 percent of deaths from all causes). 1-3 Almost every discipline in medicine must deal with this disease, from neonatology to orthopedic surgery to emergency medicine, though much of the management is performed by critical care physicians in intensive care units. The pathogenic mechanisms underlying severe sepsis and septic shock are remarkably complex. 2, 3 Microorganisms proliferate at a nidus of infection, and they or their toxins may enter the bloodstream. In response, a large number of host-derived mediators are released from plasma proteins (the coagulation, fibrinolytic, and complement systems) or cells (endothelial cells, monocyte macrophages, and neutrophils). These endogenous mediators have a profound physiologic effect on vasculature and multiorgan systems. Septic shock can produce dysfunction in the cardiovascular, respiratory, renal, hematologic, metabolic, hepatic, and neurologic systems. Death results from progressive hypotension or the failure of at least one organ. Severe sepsis (ie, sepsis plus the dysfunction of at least one organ) is associated with in-hospital mortality of approximately 30 percent, and septic shock (ie, sepsis with hypotension despite adequate fluid replacement) with in-hospital mortality of approximately 50 percent.

Current management of severe sepsis and septic shock consists of eradication of the infection (by means of surgical drainage and early administration of antimicrobial agents); cardiovascular support (early monitoring, aggressive fluid administration, the use of vasopressor agents, inotropic agents, or both, and possibly blood transfusions); pulmonary therapy (supplemental oxygen, mechanical ventilation with low tidal volumes, positive endexpiratory pressure to treat acute lung injury or acute respiratory distress syndrome); and renal replacement therapy, if indicated. Other general recommendations for the management of these conditions in the intensive care unit include main-