Suspected severe sepsis patients account for more than 500,000 ED visits annually, with respiratory and genitourinary infections being the most common causes of sepsis.4 Hospitalizations for septicemia more than doubled over the past decade, from 326,000 in 2000 to 727,000 in 2008.5 Sepsis was the seventh-leading cause of infant mortality in 2010, and the 11th-leading cause of death in adults (34,843 total) that same year.6
Approximately 0.7% of emergency department patients present with suspected severe sepsis. More than two thirds of all sepsis patients initially present to EDs, and approximately 17% of these patients reside in nursing homes.3
The incidence of severe sepsis in the U.S. is about 3.0 cases per 1,000 population.7 The incidence of sepsis and its related mortality are significantly higher in the elderly population compared to younger persons, and more than half of all sepsis patients presenting to EDs are over 65 years of age.3 The projected growth of the elderly population in the United States will contribute to an increased incidence of 1.5% each year, resulting in an estimated case load of more than 1.1 million by 2020.7
Sepsis and septic shock are the endpoints of an extremely intricate process that is not precisely understood, but involves a complex and often unbalanced interaction between the body’s inflammatory and anti-inflammatory responses to an invading microbe. When a microbe breaches the body’s protective epithelial barrier and enters the underlying tissue, it is identified by host neutrophils, macrophages, mast cells and other cells of the immune system, including natural antibodies. These cells secrete cytokines (chemical mediators) that activate the local inflammatory response, resulting in increased capillary permeability and blood flow, which in turn allows neutrophils (phagocytes) to access the infected tissue, crossing from circulation into the interstitial space. Neutrophils will then phagocytize (ingest) the invading microorganisms. Having neutrophils do their job in the interstitial space rather than the circulatory system is desirable, as proteases (digestive enzymes) and oxides are released during phagocytosis. If released in the circulatory system and not the interstitial spaces, these chemicals could result in cellular damage to tissues throughout the body.
This concept of local response to infection is important, and the body has mechanisms to suppress inflammation within the bloodstream so that a systemic response does not occur. This response includes anti-inflammatory, procoagulant and thermoregulatory actions. Anti-inflammatory actions include the release of antioxidants, anti-inflammatory mediators, cytokine antagonists and protease inhibitors. Procoagulant activity helps wall off the developing infection and prevent systemic spread, increases clot formation by decreasing the synthesis of fibrinogen, and decreases the release of antithrombin, an enzyme that inactivates several enzymes of the coagulation system. Thermoregulatory responses to infection include the creation of fever, which inhibits bacterial growth and increases the activity of neutrophils and macrophages.
Patients with sepsis are arguably still maintaining the balance between their local inflammatory and systemic anti-inflammatory responses. These may be patients experiencing a bacterial or viral infection such as the flu, pneumonia or a bladder infection. In otherwise healthy patients, over-the-counter medications or prescription medications from physicians may be sufficient to treat the illness.
Severe sepsis occurs when the body’s systemic anti-inflammatory efforts are insufficient to attenuate the massive pro-inflammatory response mounted by the body. Systemic arterial vasodilation leads to a relative hypovolemia, and an increase in systemic microvascular permeability leads to edema formation through third-spacing of fluids. In the lungs this can lead to development of acute respiratory distress syndrome (ARDS).