Chest
Critical Care: ArticlesSepsis: A New Hypothesis for Pathogenesis of the Disease Process
Section snippets
SEPSIS, SIRS, CARS, AND MARS
When the American College of Chest Physicians and Society of Critical Care Medicine convened a Consensus Conference in 1991 to address the problem of confusion over use of proper terms and definitions, the terms bacteremia, septicemia, sepsis, sepsis syndrome, and septic shock were being used almost interchangeably, which led to confusion and imprecise understanding of sepsis and related disorders. Members of the Consensus Conference agreed to a new set of definitions that could be readily
The Cytokine Cascade
The systemic response to infection is mediated via the macrophage-derived cytokines that target end-organ receptors in response to injury or infection. The inflammatory response to infection or injury is a highly conserved and regulated reaction of the organism. After recognition that a response is required, the organism (eg, a human being) produces soluble protein and lipid proinflammatory molecules that activate cellular defenses, then produces similar anti-inflammatory molecules to attenuate
Why Previous Theories were Inadequate
We have understood that a massive inflammatory reaction underlies both SIRS and MODS, but now we must understand that this reaction is only half the picture. It is now clear that quite rapidly after the first proinflammatory mediators are released, the body mounts a compensatory anti-inflammatory reaction (CARS) to the initial proinflammatory response.13 The anti-inflammatory reaction may be as large as, and sometimes even larger than, the proinflammatory response. The goal of this
Relating Clinical Responses to Cytokine Cascade
Some patients with sepsis, extensive burns, massive traumatic injury, or other severe insults show little or no evidence of a systemic inflammatory reaction or organ dysfunction, although their recovery may be protracted because of the severity of their underlying illness. In three other categories, however, are patients with sepsis or other severe insult who develop the following: a mild form of SIRS and some evidence of dysfunction in one or two organs early in their clinical course that
A New Theory of SIRS, CARS, MARS, AND MODS
Immunomodulation is a complex, overlapping network of interactions among agents that work together to overcome severe assaults on the body. Paradoxically, they also work to the body's disadvantage and cause the disruptions we call SIRS and MODS. We have presented a hypothesis-based explanation for the apparently paradoxical events observed in the critically ill (Fig 4). The five stages in the development of multiple organ dysfunction are as follows: (1) local reaction at the site of injury or
Conclusions
Balance between proinflammatory and anti-inflammatory forces could conceivably be lost: (1) when infection, burn injury, hemorrhage, etc, is so severe that the insult alone is sufficient to prompt SIRS and MODS; or (2) when patients are “preprimed” to develop SIRS and MODS by preexisting severe illness. (3) Most of the preexisting conditions are associated with abnormal cytokine levels.19
The hypothesis of prepriming rests on our understanding that a patient at risk for SIRS or MODS already has
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