Sepsis is one of the leading causes of morbidity and mortality in the United States. Centers for Disease Control and Prevention (CDC) estimates that there are more than 1 million cases of sepsis each year. Sepsis and septic shock cause approximately 250,000 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 resulting in sepsis continues to rise due to antibiotic-resistant organisms plus the increased use of immunosuppressive drugs, intravenous and urinary catheters, and prosthetic implants.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (see Singer M, et al. JAMA. 2016;315, 801). Evidence of organ dysfunction includes clinical and laboratory abnormalities of the respiratory system, coagulation, liver, cardiovascular system, nervous system, and kidneys (see eTable 79–1).
eTABLE 79–1Evidence of Organ Dysfunction in Severe Sepsis |Favorite Table|Download (.pdf) eTABLE 79–1 Evidence of Organ Dysfunction in Severe Sepsis
|Clinical Evidence ||Comment |
|Hypoxemia ||Reduced arterial blood oxygen caused by acute respiratory distress syndrome (ARDS) |
|Oliguria or elevated creatinine ||Evidence of renal failure |
|Lactic acidosis ||Elevated serum lactate caused by end-organ hypoperfusion |
|Thrombocytopenia ||Reduced number of platelets caused by disseminated intravascular coagulation |
|Altered mental status ||Caused by hypoxia to brain and manifested by confusion or obtundation |
|Elevated liver function tests ||Elevated bilirubin and transaminase caused by hepatocyte damage |
|Global hypokinesis seen on echocardiography ||Evidence of myocardial dysfunction |
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 septic patients who have persistent hypotension (mean arterial blood pressure below 65 mm Hg) and elevated serum lactate despite adequate intravenous fluids.
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% have organ system infections, most often in the respiratory tract, urinary tract, gall bladder or intestine, without detectable bacteremia.
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.
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 in conjunction with LPS-binding protein binds to Toll receptor 4 on the surface of the macrophage. This stimulates the production of interleukin-1 (IL-1) causing fever, nitric oxide causing vasodilation and hypotension, and tumor necrosis factor (TNF) causing vascular permeability, also contributing to hypotension. ...