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DEFINITIONS

  • Sepsis: a life-threatening organ dysfunction caused by a dysregulated host response to infection.

  • Septic shock: a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities lead to substantially increased mortality risk. Pts need vasopressor therapy to elevate mean arterial pressure to ≥65 mmHg with a serum lactate concentration >2.0 mmol/L despite adequate fluid resuscitation.

ETIOLOGY

  • Pneumonia is the most common antecedent infection, accounting for ∼50% of cases of sepsis; intraabdominal and genitourinary infections are the next most common sources.

  • Blood cultures are positive in approximately one-third of cases.

  • Microbiologic results have revealed that 62% of isolates are gram-negative bacteria (most commonly Pseudomonas aeruginosa, Klebsiella spp., and Escherichia coli), 47% are gram-positive bacteria (most commonly Staphylococcus aureus and Streptococcus pneumoniae), and 19% are fungi, with some cultures being polymicrobial.

EPIDEMIOLOGY

  • The incidence of sepsis in the United States is >2 million cases each year, with shock documented in ∼30% of cases (19 per 1000 hospitalized encounters). This figure represents a rise of nearly 50% in the past decade; the reasons for this increase may include nonmedical issues.

  • The rates of sepsis and septic shock are likely to be much higher in low- and middle-income countries, with mortality rates >40%.

PATHOPHYSIOLOGY

  • The host response evolves throughout the pt’s course, with early proinflammatory reactions directed at eliminating pathogens responsible for “collateral” tissue damage and subsequent anti-inflammatory responses implicated in increased susceptibility to secondary infections.

  • Hosts have numerous pattern recognition receptors whose recognition of highly conserved pathogen-associated molecular patterns (PAMPs; e.g., lipopolysaccharide) and damage-associated molecular patterns (DAMPs; e.g., extracellular RNA, DNA, and histones) triggers the release of inflammatory cytokines and activation of the complement system and platelet-activating factor.

  • Impaired tissue oxygenation plays a key role in sepsis-associated organ failure.

CLINICAL FEATURES

  • The two most commonly affected organ systems are the respiratory system, in which dysfunction classically manifests as the acute respiratory distress syndrome, and the cardiovascular system, in which dysfunction typically presents as hypotension.

  • Acute kidney injury, which is found in >50% of septic pts, increases the risk of in-hospital death by six- to eightfold.

  • Typical CNS dysfunction presents as coma or delirium.

  • Many other abnormalities occur in sepsis, including ileus, DIC, and sick euthyroid syndrome. Adrenal dysfunction, the diagnosis of which is difficult to establish in these pts, is more commonly due to reversible dysfunction of the hypothalamic–pituitary axis or tissue glucocorticoid resistance than to direct damage to the adrenal gland.

DIAGNOSIS

There is no gold-standard method for determining whether a pt is septic.

  • In pts with a suspected infection, the SOFA (sepsis-related organ failure assessment) score synthesizes vital signs and lab tests across six organ systems to help define whether the pt is septic. The score ranges from 0 to 24; pts ...

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