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INTRODUCTION

GUIDING QUESTIONS

  1. How is sepsis defined?

  2. What are PAMPs and how do they mediate sepsis?

  3. What are DAMPs and what role do they play in sepsis?

  4. What are PRRs and how do they mediate inflammation?

  5. What happens to immune function after recovery from acute sepsis?

  6. What is a “superantigen,” and which bacteria produce them?

  7. What are the clinical clues that suggest sepsis?

  8. What are the most important therapeutic interventions for sepsis and how quickly should they be started?

POTENTIAL SEVERITY

A life-threatening syndrome that must be recognized and treated quickly to prevent progression to irreversible shock. Early treatment saves lives.

PREVALENCE

Sepsis is diagnosed in 5.9% of hospitalized patients in the United States and is associated with an in-hospital mortality of 15.6%. These figures translate into approximately 1.7 million hospitalizations for adult sepsis and 270,000 deaths per year in the United States. Sepsis is one of the leading causes of preventable death in our hospitals, and throughout the world.

DEFINITIONS

The definition of sepsis has recently been changed in recognition of the poor sensitivity and specificity of previous definitions, and the lack of evidence that the sepsis syndrome follows a simple continuum from systemic inflammation to shock and organ failure. Original investigations suggested that the sepsis syndrome was primarily the consequence of excessive inflammation; however, more recent research reveals that both inflammatory and anti-inflammatory mediators are activated when bacteria gain access to the blood stream. An expert panel has recommended discarding the terms SIRS, sepsis syndrome, septicemia, and severe sepsis in favor of two stages of disease: sepsis and septic shock. Sepsis is now defined as “life threatening organ dysfunction caused by dysregulation of the immune response to infection.” And septic shock is defined as a “subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality.” These new definitions are clinically operationalized by applying objective criteria that have the potential to improve the sensitivity and specificity of both sepsis and septic shock (see section “About the Diagnosis of Sepsis”).

KEY POINTS About the Prevalence and Definitions of Sepsis Syndrome

  1. Prevalence is 1.7 million cases per year in the United States.

  2. Overall mortality is approximately 15%.

  3. Sepsis is defined as life-threatening organ dysfunction caused by dysregulation of the immune response to infection.

  4. Septic shock is a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality.

PATHOGENESIS

When bacteria or fungi invade the intravascular space, they come in contact with endothelial and immune cells that are continually sampling the environment. These cells recognize pathogen-associated molecular patterns (PAMPs), molecules that share different general patterns that warn of the presence of an invading pathogen. One of the first PAMPs to be discovered was lipopolysaccharides or LPS ...

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