Management of Sepsis: The Surviving Sepsis Guidelines for Early Therapy

Hospital Physician June 2007 21 Sepsis is a common condition that is associated with poor patient outcomes and high financial costs. An estimated 750,000 cases of sepsis occur each year. Because sepsis is more common in elderly patients, its incidence is expected to rise as the US population ages.1 Despite recent advances in management and therapy, the mortality rate from severe sepsis remains high at approximately 28%.1 The average treatment cost per case of sepsis is approximately $22,000, and the cost of treatment increases significantly with the number of dysfunctional organs.1 Given the substantial clinical burden of sepsis, physicians should be knowledgeable about evidence-based interventions for acute management of septic patients. Sepsis can be viewed as a heterogeneous syndrome with widely differing pathophysiologic mechanisms and outcomes.2 The pathogenesis of severe sepsis and septic shock is remarkably complex.3 The syndrome starts with an inciting event, usually microorganism proliferation at a nidus of infection, that leads to a complex inflammatory reaction and the release of a large number of host-derived immune mediators (eg, interleukins, tumor necrosis factor-α). These mediators in turn have a profound physiologic effect on the vasculature and organ systems. Septic shock can produce cardiovascular, respiratory, renal, hematologic, metabolic, hepatic, and neurologic dysfunction. Death generally results from progressive hypotension or the failure of at least 1 organ system.4 For nearly a century, sepsis had been defined as the systemic response to an infection.5 In a 1992 consensus conference, the American College of Chest Physicians and the Society of Critical Care Medicine first delineated criteria for defining disease states in the sepsis continuum and introduced the term systemic inflammatory response syndrome (SIRS), which does not require the presence of infection (Table 1).6 The 2001 International Sepsis Definition Conference attempted to improve on the specificity of these definitions by elaborating common clinical and laboratory manifestations of the disorder (Table 2).7 One of the goals of creating these definitions was to help physicians recognize patients at risk for severe sepsis and intiate therapy promptly. In order to reflect the many prognostic factors in sepsis and provide a hypothesis-generating model for future research, the PIRO (Predisposing factors, nature of Insult, intensity of Response, number of Organ dysfunction) grading system was also proposed.7 Another step in the evolution of sepsis management occurred in 2004 when the guidelines from the Surviving Sepsis Campaign (SSC) were published.8 C l i n i c a l R e v i e w A r t i c l e