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INTRODUCTION AND DEFINITIONS
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Sepsis is a common and deadly disease. More than two millennia ago, Hippocrates wrote that sepsis was characterized by rotting flesh and festering wounds. Several centuries later, Galen described sepsis as a laudable event required for wound healing. Once the germ theory was proposed by Semmelweis, Pasteur, and others in the nineteenth century, sepsis was recast as a systemic infection referred to as “blood poisoning” and was thought to be due to pathogen invasion and spread in the bloodstream of the host. However, germ theory did not fully explain sepsis: many septic patients died despite successful removal of the inciting pathogen. In 1992, Bone and colleagues proposed that the host, not the germ, was responsible for the pathogenesis of sepsis. Specifically, they defined sepsis as a systemic inflammatory response to infection. Yet sepsis arose in response to many different pathogens, and septicemia was neither a necessary condition nor a helpful term. Thus, these investigators instead proposed the term severe sepsis to describe cases where sepsis was complicated by acute organ dysfunction and the term septic shock for a subset of sepsis cases that were complicated by hypotension despite adequate fluid resuscitation along with perfusion abnormalities.
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In the past 20 years, research has revealed that many patients develop acute organ dysfunction in response to infection but without a measurable inflammatory excess (i.e., without the systemic inflammatory response syndrome [SIRS]). In fact, both pro- and anti-inflammatory responses are present along with significant changes in other pathways. To clarify terminology and reflect the current understanding of the pathobiology of sepsis, the Sepsis Definitions Task Force in 2016 proposed the Third International Consensus Definitions specifying that sepsis is a dysregulated host response to infection that leads to acute organ dysfunction. This definition distinguishes sepsis from uncomplicated infection that does not lead to organ dysfunction, a poor course, or death. In light of the wide variation in the ways that septic shock is identified in research, clinical, or surveillance settings, the Third International Consensus Definitions further specified that septic shock be defined as a subset of sepsis cases in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality risk.
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To aid clinicians in identifying sepsis and septic shock at the bedside, new “Sepsis-3” clinical criteria for sepsis include (1) a suspected infection and (2) acute organ dysfunction, defined as an increase by two or more points from baseline (if known) on the sequential (or sepsis-related) organ failure assessment (SOFA) score (Table 297-1). Criteria for septic shock include sepsis plus the need for vasopressor therapy to elevate mean arterial pressure to ≥65 mmHg with a serum lactate concentration >2.0 mmol/L despite adequate fluid resuscitation.
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