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KEY POINTS
Sepsis is a dysregulated host immune response to infection.
Septic shock is sepsis with vasodilatory shock requiring intravenous vasopressors and with a serum lactate level greater than 2 mmol/L and has a greater mortality than sepsis alone.
Acute organ dysfunction is a key element of sepsis and can manifest in any organ. Frequent manifestations include shock, respiratory failure, acute kidney injury, hematologic disturbances, metabolic dysfunction, and/or neurologic decline.
Sepsis results in a complex set of interactions between the inciting microbes and the host immune response, which trigger the inflammatory cascade and coagulation pathway. It is not well understood why some individuals have a dysregulated response that provokes or perpetuates organ dysfunction.
Sepsis can be due to infection with any organism—classically gram-negative bacteria, but an increasing number of infections are now due to gram-positive organisms and fungal organisms. The inciting organism remains unknown in many cases of both sepsis and septic shock.
Early recognition is key to the evaluation and management of patients with possible sepsis, and includes a thorough history and physical examination, relevant laboratory studies including lactate level, an evaluation of potential infectious sources and organisms, and appropriate imaging studies.
The most common parameters used in monitoring sepsis patients are arterial blood pressure, pulse oximetry, central venous pressure, central venous or mixed venous oxygen saturation, and blood lactate. Other parameters that may guide therapy include cardiac output and systemic vascular resistance. Each of these parameters is complementary and may assist in both the early and late management of sepsis, organ dysfunction, and shock.
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Sepsis has been a life-threatening medical condition since the first steps in evolution. Antimalarial compounds were prescribed for fever in China as early as 2735 BC and Hippocrates recognized the anti-infective properties of wine and vinegar around 400 BC. The basic premise of infection and immune response were recognized from the time that Marcus Terentius Varro in 100 BC noted that “small creatures invisible to the eye, fill the atmosphere, and breathed through the nose cause dangerous diseases.” These early concepts carried through the Black Death plague of the middle ages and Janssen’s invention of the microscope, to Louis Pasteur’s germ therapy, and on to Ignaz Semmelweis and Joseph Lister’s antisepsis practices. At the turn of the last century, William Osler recognized that “the patient appears to die from the body’s response to infection rather than from it.”
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Despite clear advances in understanding infection and the immune response, sepsis was not recognized as a specific medical entity deserving of recognition and focused study until the 1970s. Since then, the definition of sepsis has evolved as our understanding of the underlying pathophysiology has grown. In 1992, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) jointly developed the first set of consensus definitions for sepsis and related disorders (referred ...