Sepsis

Last updated: May 24, 2022

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Sepsis is an acute life-threatening condition characterized by organ dysfunction due to a dysregulated immune response to infection. Without prompt intervention, patients frequently progress to septic shock and multiple organ failure. The precipitating infection is often bacterial, typically originating in the respiratory, genitourinary, or gastrointestinal systems or in the skin or soft tissue. Clinical features include fever, tachycardia, confusion, and signs of the primary infection. Sepsis screening tools incorporating common clinical variables and laboratory values are used to facilitate early identification of sepsis. Favorable patient outcomes rely on early detection, effective resuscitation measures (e.g., aggressive fluid therapy and appropriate use of vasopressors), and early administration of antibiotics. The diagnostic workup of sepsis should occur in parallel with resuscitation efforts and focuses on identifying the site of infection and causative pathogen for definitive treatment.

Definitions and criteria in this section apply to adult patients.

Third International Consensus Definitions for Sepsis and Septic Shock [1][2]

  • Sepsis: a severe, life-threatening condition that results from a dysregulation of the patient's response to an infection, causing tissue and organ damage and subsequent organ dysfunction [1]
  • Septic shock: a sepsis syndrome accompanied by circulatory and metabolic abnormalities that can significantly increase mortality [1]

Organ dysfunction secondary to sepsis is defined as an acute increase of ≥ 2 in the total SOFA score due to the infection.

Other definitions of sepsis syndromes [1][3][4][5][6]

  • Systemic inflammatory response syndrome (SIRS) : a group of physiological and immune-mediated reactions that are triggered in response to an infectious or noninfectious insult (e.g., an acute inflammatory process or trauma) [1][3]
  • Sepsis: ≥ 2 SIRS criteria PLUS a suspected or confirmed underlying infection [1]
  • Severe sepsis: sepsis PLUS dysfunction of at least one organ or system [1]
  • Multiple organ dysfunction syndrome (MODS) : [1]
    • Progressive, but potentially reversible, dysfunction of several organs and/or systems [7]
    • The more organs that are affected, the greater the mortality risk.
  • Bacteremia: the presence of viable bacteria in the bloodstream, with or without clinical signs of infection [8]

Sequential organ failure assessment score (SOFA score) [1][9]

  • Used in critical care settings as a tool to identify organ failure and predict mortality
  • The score should be calculated after 24 hours of ICU admission and then every 48 hours.
  • Should not be used to diagnose sepsis
SOFA score [1][10]
System 0 points 1 point 2 points 3 points 4 points

Respiration

PaO2/FiO2 (mm Hg)

  • ≥ 400
  • < 400
  • < 300
  • < 200 with respiratory support
  • < 100 with respiratory support

Coagulation

Platelets x 103/mm3

  • ≥ 150
  • < 150
  • < 100
  • < 50
  • < 20

Liver

Bilirubin (mg/dL)

  • < 1.2
  • 1.2–1.9
  • 2.0–5.9
  • 6.0–11.9
  • > 12.0

Cardiovascular system

  • MAP ≥ 70 mm Hg
  • MAP < 70 mm Hg

Central nervous system

Glasgow Coma Scale

  • 15
  • 13–14
  • 10–12
  • 6–9
  • < 6

Renal function

Creatinine (mg/dL)

  • < 1.2
  • 1.2–1.9
  • 2.0–3.4
  • 3.5–4.9
  • OR urine output < 500 mL/day
  • > 5.0
  • OR urine output < 200 mL/day

Interpretation

  • SOFA score (≥ 2 points): overall mortality risk ∼ 10%

The SOFA score is not designed to diagnose sepsis.

See also “Etiology of bloodstream infections.”

Implanted devices are an important risk factor and a common source of infection. [1]

References:[12][13][14][15][16][17][18]

Sepsis is a hyperinflammatory systemic reaction.

  1. Local activation of inflammatory mediators (complement system, mast cells, macrophages) results in vessel dilation and further release of proinflammatory cytokines (esp. TNFα, IL-1).
  2. Generalized endothelial disruption → capillary leak → generalized edema due to a shift of intravascular fluid and albumin into the surrounding tissue
  3. Intravascular hypovolemia; → excessive triggering of the extrinsic coagulation cascade disseminated intravascular coagulation (DIC) and microvascular thrombosis
  4. Decreased oxygen utilization and tissue ischemia; → widespread cellular injury → organ dysfunction (commonly multisystem)

An adequate immune response requires a balance between proinflammatory (antiinfectious) and antiinflammatory signals!

The following recommendations are consistent with the 2021 Surviving Sepsis Campaign guidelines and the American College of Emergency Physicians (ACEP) task force consensus statement for adults with suspected sepsis in the emergency department. [2][19]

Sepsis is a medical emergency. Be vigilant for early signs of sepsis and begin treatment as soon as sepsis is suspected.

Approach [2]

Perform diagnostics and treatment simultaneously in patients with suspected sepsis.

Sepsis management is an iterative process requiring frequent reassessments. Favorable outcomes depend on early detection, effective resuscitation, and early administration of antibiotics. [2][19]

Hour-1 bundle for sepsis [2][9][23]

Hour-1 bundle: lactate + cultures + fluids + vasopressors + antibiotics

Disposition [2]

The main goals of the diagnostic workup in a patient with suspected sepsis are to determine the presence and severity of organ dysfunction and to identify the source of infection. See the “Definitions” section for diagnostic criteria. [1][4][23]

Positive cultures are not mandatory for the diagnosis of sepsis.

Sepsis screening tools [2][19]

  • Goal: early identification of patients with sepsis to reduce mortality [2][25]
  • Commonly used tools [25]
    • SIRS criteria [1][3]
    • Quick SOFA score (qSOFA) [26]
      • Can predict poor outcomes; not recommended as a sole screening tool for sepsis [2][27][28]
      • Considered positive if ≥ 2 of the following are present:
  • Limitations: Accuracy is low and can vary. [2][28][29]

The qSOFA score is not recommended as a sole screening tool for sepsis or septic shock. [2]

Laboratory studies

In addition to serum lactate and blood cultures (at least two sets), obtain the following studies to support the diagnosis and evaluate for organ dysfunction.

Identifying the source of infection

Microbiology

When possible, obtain the additional samples before starting antibiotic treatment, but do not delay antibiotics if samples are not rapidly available.

Imaging

Direct decisions based on clinical suspicion. Examples of commonly performed imaging include:

See also “Immediate hemodynamic support” and “Septic shock.”

IV fluids [30][2]

Vasopressors for septic shock [2][24]

See “Septic shock” and “Vasopressors” for further details.

Consider starting vasopressor infusion through a peripheral IV to avoid delays while awaiting central venous access. [2]

Hemodynamic reassessment in sepsis [2][19][24][31]

Continuously monitor hemodynamic parameters and volume status to guide IV fluids and/or vasopressor therapy.

If possible, use invasive BP monitoring to facilitate continuous reassessment. [2]

Respiratory support [2][37][38]

Respiratory dysfunction is a common feature of sepsis. Patients with sepsis frequently have tachypnea, signs of increased work of breathing, and/or hypoxia.

Shock and metabolic acidosis are both associated with a high risk of peri-intubation mortality. [4][40]

Corticosteroids [2][19]

Approach

Empiric antibiotic therapy for sepsis [9][41][42][43][44]

There is little consensus regarding the optimal empiric antibiotic regimens for patients with sepsis and septic shock, especially if the source of infection is unclear.

Evident source of infection [4]

If the source of infection is clear, follow local hospital protocols to administer antibiotics that cover the most common causative pathogens.

Unclear source of infection [41][42][43][52]

The following regimens are examples commonly mentioned in the literature; follow local hospital protocols when available.

Empiric antibiotic regimens for sepsis with unclear source
Patient characteristics Commonly used regimens

Unknown risk factors

At risk for specific pathogens

Neutropenia

Antifungal therapy [9]

Source control for sepsis [2][24]

Identify and eliminate sources of infection that cannot be adequately treated with antimicrobials as soon as possible (e.g., within 6–12 hours). [2]

The following is a list of noninfectious conditions that may mimic sepsis. [4][24]

Critical illness polyneuropathy is a common cause of prolonged weaning from mechanical ventilation in patients with sepsis!

We list the most important complications. The selection is not exhaustive.

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