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Information ⬇

[Section Outline]

Definitions !!navigator!!

  • 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 !!navigator!!

  • 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 !!navigator!!

  • 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 !!navigator!!

  • 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 !!navigator!!

  • 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 !!navigator!!

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 with ≥2 new SOFA points are considered septic and are at ≥10% risk of in-hospital death.
  • The quickSOFA (qSOFA) score is a simpler algorithm that can be computed at the bedside. Pts are given 1 point each for systolic hypotension (≤100 mmHg), tachypnea (≥22 breaths/min), or altered mentation. A qSOFA score of ≥2 has a predictive value for sepsis similar to that of the SOFA score.
  • Lactate levels are typically elevated in sepsis (≥2.5 mmol/L) but should not be used as a stand-alone biomarker for sepsis as they can occur in many other clinical conditions or may simply represent impaired clearance.
TREATMENT

Sepsis and Septic Shock

  • Early treatment of sepsis and septic shock is best summarized by two “bundles” of care:
    1. Within 3 h of presentation (ideally within the first hour), the pt should be given appropriate broad-spectrum antibiotics (see Table 14-1 Initial Antimicrobial Therapy for Severe Sepsis with No Obvious Source in Adults with Normal Renal Function for regimens), with collection of blood for culture before antibiotic administration and measurement of serum lactate levels.
      • For every 1-h delay in the initiation of antibiotic administration to pts with sepsis, there is a 3-7% increase in the odds of in-hospital death.
    2. Within 6 h of presentation, the pt should receive an IV fluid bolus and treatment with vasopressors for persistent hypotension or shock, and serum lactate levels should be re-measured.
      • More than 30% of pts with severe sepsis require source control, mainly for abdominal, urinary, and soft-tissue infections.
  • Subsequent treatment of sepsis requires ongoing hemodynamic monitoring, support of organ function (e.g., provision of IV fluids, administration of blood products, and respiratory support, as needed), and-once the pt's condition stabilizes-de-escalation of care.

Prognosis !!navigator!!

The mortality rate from sepsis and septic shock is ∼20%. Survivors remain at increased risk of death in the following months and years, and they often suffer from impaired physical or neurocognitive dysfunction, mood disorders, and low quality of life.

Prevention !!navigator!!

The number of sepsis cases could be reduced by avoiding unnecessary antibiotic use, limiting the use of indwelling devices and catheters, minimizing unnecessary immune suppression, and increasing adherence to infection control programs at hospitals and clinics.

Outline ⬆

Section 2. Medical Emergencies