New Concepts and Emerging Issues in Sepsis

Severe sepsis and septic shock are manifestations of the host's immune uncontrolled response to infection. The term sepsis is a poorly defined, but commonly used term in the medical literature, and it is derived from the Greek word “Sépsis” meaning decay. Sepsis is best defined as a life-threatening condition or complex caused by overwhelming inflammatory response to infection associated with dysregulation of the body's immune mechanism. Sepsis is the leading cause of death in critically ill patients in most intensive care units (ICUs). It has been estimated that in the United States sepsis develops in 750,000 people annually, and more then 210,000 of those die(1,2)! Infants and children in >42,000 cases of severe sepsis occur annually in the United States and millions worldwide.(2) The incidence of septicemia and sepsis have been increasing in the past 3 decades in many countries because of several factors, including longer lifespan with a greater population of the elderly; treatment with immunosuppressives with a greater number of subjects with organ transplantations and cancers; use of invasive and novel treatment with prosthesis, long-term or permanent catheters; and the expanding acquired immunodeficiency syndrome (AIDS) epidemic. In national hospital discharge surveys in the United States, the incidence of septicemia had increased from 73.6 per 100,000 patients in 1979 to 175.9 per 100,000 patients in 1987.(3) Surveys in the United States and Europe have estimated that severe sepsis accounts for 2–11& of all admission to hospital or ICUs.(1) Observational studies indicate that 30–50& of the cases are admitted through the emergency department, rather than developing in hospitals.(4,5) The incidence of sepsis appears to continue to increase by 8.7& annually (with an adjusted rate of increase of nearly 300& from 1979 to 2000),(6) but may be greater in the United States (US) with an incidence of 240–300 per 100,000 populations, compared to some European countries (Austria, Germany) with rates of 54–116 per 100,000 population.(7) Despite progress in our understanding of the pathophysiology of sepsis, the mortality rate is still high (in those with severe sepsis and septic shock). Although the mortality rate overall has fallen in the United States from 27.8& to 17.9& in septic patients over 2 decades, the mortality rate was 30& in those with any organ failure and 70& in those with multiple organ failure.(6) Patients with infections and severe sepsis require prolonged stay in ICU and hospital, resulting in increase health care costs. Estimates of direct costs per sepsis patient in the United States are about $50,000 whereas European costs are lower, $26,450–33,350.(7) Thus a crude estimate of the direct annual cost of severe sepsis in the United States is about $17.0 billion.(1)