Sepsis is a life-threatening condition that arises when the body’s response to infection injures its own tissues and organs.^[1] Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion.^[2] There may also be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection. In the very young, old, and people with a weakened immune system, there may be no symptoms of a specific infection and the body temperature may be low or normal rather than high.^[3] Severe sepsis is sepsis causing poor organ function or insufficient blood flow. Insufficient blood flow may be evident by low blood pressure, high blood lactate, or low urine output. Septic shock is low blood pressure due to sepsis that does not improve after reasonable amounts of intravenous fluids are given.^[4]

Sepsis is caused by an immune response triggered by an infection.^[3][5] The infection is most commonly bacterial, but it can be from fungi, viruses, or parasites.^[3] Common locations for the primary infection include lungs, brain, urinary tract, skin, and abdominal organs. Risk factors include young or old age, a weakened immune system from conditions such as cancer or diabetes, and major trauma or burns.^[2] Diagnosis was based on meeting at least two systemic inflammatory response syndrome (SIRS) criteria due to a presumed infection.^[3] In 2016 screening by SIRS was replaced with qSOFA which is two of the following three: increased breathing rate, change in level of consciousness, and low blood pressure.^[6] Blood cultures are recommended preferably before antibiotics are started; however, infection of the blood is not required for the diagnosis.^[3] Medical imaging should be done to look for the possible location of infection.^[4] Other potential causes of similar signs and symptoms include anaphylaxis, adrenal insufficiency, low blood volume, heart failure, and pulmonary embolism among others.^[3]

Sepsis is usually treated with intravenous fluids and antibiotics. Antibiotics are typically given as soon as possible. This is often done in an intensive care unit. If fluid replacement is not enough to maintain blood pressure, medications that raise blood pressure can be used. Mechanical ventilation and dialysis may be needed to support the function of the lungs and kidneys, respectively.^[2] To guide treatment, a central venous catheter and an arterial catheter may be placed for access to the bloodstream. Other measurements such as cardiac output and superior vena cava oxygen saturation may be used. People with sepsis need preventive measures for deep vein thrombosis, stress ulcers and pressure ulcers, unless other conditions prevent such interventions. Some might benefit from tight control of blood sugar levels with insulin.^[4] The use of corticosteroids is controversial.^[7] Activated drotrecogin alfa, originally marketed for severe sepsis, has not been found to be helpful and was withdrawn from sale in 2011.^[8]

Disease severity partly determines the outcome with the risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80%.

The term “σήψις”^[79] (sepsis) was introduced by Hippocrates in the fourth century BC, and it meant the process of decay or decomposition of organic matter.^[80] In the eleventh century, Avicenna used the term “blood rot” for diseases linked to severe purulent process. Though severe systemic toxicity had already been observed, it was only in the 19th century that the specific term – sepsis – was used for this condition.

The terms septicemia, also spelled septicaemia, and blood poisoning referred to the microorganisms or their toxins in the blood and are no longer commonly used.^[12][11]

By the end of the 19th century, it was widely believed that microbes produced substances that could injure the mammalian host and that soluble toxins released during infection caused the fever and shock that were commonplace during severe infections. Pfeiffer coined the term endotoxin at the beginning of the 20th century to denote the pyrogenic principle associated with Vibrio cholerae. It was soon realised that endotoxins were expressed by most and perhaps all gram-negative bacteria. The lipopolysaccharide character of enteric endotoxins was elucidated in 1944 by Shear.^[81] The molecular character of this material was determined by Luderitz et al. in 1973.^[82]

It was discovered in 1965 that a strain of C3H/HeJ mice were immune to the endotoxin-induced shock.^[83] The genetic locus for this effect was dubbed Lps. These mice were also found to be hypersusceptible to infection by gram-negative bacteria.^[84] These observations were finally linked in 1998 by the discovery of the toll-like receptor gene 4 (TLR 4).^[85] Genetic mapping work, performed over a period of five years, showed that TLR4 was the sole candidate locus within the Lps critical region; this strongly implied that a mutation within TLR4 must account for the lipopolysaccharide resistance phenotype. The defect in the TLR4 gene that led to the endotoxin resistant phenotype was discovered to be due to a mutation in the cytoplasm.^[86]

Society and culture

Economics

Sepsis was the most expensive condition treated in U.S. hospital stays in 2011, at an aggregate cost of $20.3 billion for nearly 1.1 million hospitalizations.^[87] Costs for sepsis hospital stays more than quadrupled since 1997 with an 11.5 percent annual increase.^[88] By payer, it was the most costly condition billed to Medicare, the second-most costly billed to Medicaid and the uninsured, and the fourth-most costly billed to private insurance.^[