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Sepsis is one of the leading causes of morbidity and mortality in the United States. Centers for Disease Control and Prevention (CDC) estimates that more than 1.7 million adults in America develop sepsis each year. Sepsis and septic shock cause approximately 270,000 deaths annually, have fatality rates of 30% to 50% in older patients, and are estimated to cost more than 30 billion dollars each year. The incidence of infections that result in sepsis continues to rise with the increased incidence of antibiotic-resistant organisms along with the increased use of immunosuppressive drugs, intravenous and urinary catheters, and prosthetic implants.
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Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence of organ dysfunction includes clinical and laboratory abnormalities of the respiratory system, coagulation, liver, cardiovascular system, nervous system, and kidneys (Table 79–1).
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A subset of patients with sepsis can develop septic shock, which is defined by profound cellular abnormalities and inadequate organ perfusion. Clinically, septic shock can be identified in patients with sepsis who also have persistent hypotension (mean arterial blood pressure below 65 mm Hg) and elevated serum lactate despite adequate intravenous fluids.
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Bacteremia is an associated term, defined as the presence of bacteria in the blood stream. Approximately 25% of patients with sepsis have detectable bacteremia. The remaining 75% without bacteremia have organ system infections, most often in the respiratory tract, urinary tract, gall bladder or intestine. Sepsis without bacteremia may also occur as a result of infection with viruses, fungi, or protozoa.
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Sepsis results from the interaction of the infectious agent, usually bacteria, with the host’s immune, cardiovascular, neuronal, metabolic, and coagulation systems. Some degree of inflammatory response to infection is normal, but when this response is dysregulated, an excess of pro- and anti-inflammatory mediators leads to organ dysfunction.
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Sepsis caused by gram-negative bacteria is mediated primarily by endotoxin, also known as lipopolysaccharide (LPS). The main effects of LPS are caused by its lipid A component. Lipid A combines with LPS-binding protein, and together are bound by Toll receptor 4 (TLR4), a pattern recognition receptor (PRRs) on the surface of macrophages ...