Sepsis

he burden of sepsis on our health care system is signif- icant, with approximately 750,000 cases per year in the United States, 215,000 resultant deaths, and annual costs of $16.7 billion nationally (1). Organ failure is a significant contributor to mortality, with renal failure occurring in approx- imately 15% of patients (2). In a large registry of critically ill patients with acute renal failure, in 19% of whom was sepsis identified as the presumed cause, in-hospital mortality was 37% with a combined outcome of death or dialysis dependence in 50% (3). Clinicians are challenged to manage this disease in an aging population with multiple comorbidities, immunosup- pression, and a changing pattern of causative microorganisms (2,4). The increasing incidence of sepsis and the unacceptably high mortality rates associated with the disease have led to global efforts to understand pathophysiology, improve early diagno- sis, and standardize management (5). Understanding the spec- trum of the disease is important for gauging severity, deter- mining prognosis, and developing methods for standardization of care in sepsis. At an international consensus conference in 1991, sepsis was defined as the systemic inflammatory response syndrome (SIRS) with a suspected source of infection. SIRS is defined as two or more of the following perturbations: Tem- perature 38 or 36°C; heart rate 90 beats per minute; respi- ratory rate 20 breaths per minute or Paco2 32 mmHg; and white blood cell count 12,000/mm 3 , 4000/mm 3 ,o r10% immature band forms. Organ dysfunction and hypoperfusion abnormalities characterize severe sepsis, and septic shock in- cludes sepsis-induced hypotension despite adequate fluid re- suscitation (6). These definitions allowed for a more uniform approach to clinical trials, hypothesis generation, and the care of the patient with sepsis. The use of SIRS criteria for the identification of sepsis have been believed by many to be arbitrary and nonspecific. In 2001, the terminology was revisited in another consensus conference. At that time, the primary categories of sepsis, severe sepsis, and septic shock were confirmed as the best descriptors for the disease process. The primary change introduced was a more comprehensive list of signs and symptoms that may accom- pany the disease. In addition, a staging system was proposed for the purpose of incorporating both host factors and response to a particular infectious insult. This concept, termed PIRO (predisposition, infection, response, organ dysfunction) (7) speaks to the need to define, diagnose, and treat patients with sepsis more precisely because a variety of evidence-based in- terventions now exist to improve outcomes (8-10) in severe sepsis and septic shock. The PIRO model remains hypothetical and is being evaluated in several studies.