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Sepsis is a heterogeneous syndrome characterized by widespread inflammation and organ distress initiated by any type of microorganism. Invasion of the blood is not necessary to develop or identify sepsis, which is determined by the host response. As sepsis severity increases, a multifactorial series of events leads to impairments in perfusion, oxygen delivery, and direct cellular damage secondary to inflammation. Eventually, multisystem organ failure occurs, and mortality is high.

The varying clinical presentation leads to a wide range of estimates of the annual incidence of severe sepsis, ranging from 300 to 1000 cases per 100,000 persons per year,1 and most patients have initial hospital care in the ED. The sepsis incidence is increasing for multiple reasons, including an aging patient population.2

Most patients with sepsis spend several hours in the ED, and once admitted, more than half will require care in an intermediate or intensive care unit.2 Sepsis is the leading cause of hospital death, with mortality rates improved from a decade ago but still high, approximately 15% to 20%3 in optimal clinical trial scenarios.4,5 This hospital mortality rate approaches 50% in the sicker subset of those with septic shock.6 Sepsis hospital mortality exceeds that of many other high-visibility acute care conditions.7-9 Morbidity is common, even after surviving a year, with a long-term deficit in cognition and functioning prevalent.10 Estimates from 10 years ago suggest annual national costs reaching $16.7 billion,2 which has certainly increased in the past decade. Sepsis is the single most expensive inpatient condition.

Gram-positive bacteria are the predominant pathogens of sepsis.11 Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and other multidrug-resistant organisms are common organisms.12 Fungal sources are more common now, particularly in immunosuppressed patients. The most likely causative microorganism varies based on the likelihood of exposure to drug-resistant microorganisms (due to recent healthcare exposures) and the anatomic site of infection.


Sepsis syndromes exist on a continuum and are defined based on the presence of a systemic, dysfunctional host response that leads to organ failure.13,14 Historic and more recent definitions are often not sensitive or specific. Previously, sepsis was a suspected or confirmed infection with evidence of systemic inflammation (demonstrated either through evidence of the systemic immune response syndrome or laboratory abnormalities). Severe sepsis was sepsis plus evidence of new organ dysfunction thought to be secondary to tissue hypoperfusion. Septic shock exists when cardiovascular failure occurs and carries the worst prognosis.

In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock removed severe sepsis as a term and narrowed the definition of septic shock (Table 151-1).15 In Third International Consensus Definitions for Sepsis and Septic Shock, patients with suspected or proven infection, signs of systemic inflammation (without strict definitions), and organ failure (defined ...

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