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Sepsis

Last updated: August 2, 2021

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Sepsis is an acute life-threatening condition characterized by organ dysfunction due to a dysregulated immune response to infection. Some patients progress to failure in the physiologic function of several organs and systems (multiple organ dysfunction syndrome) or septic shock, in which specific circulatory and metabolic abnormalities are present (i.e., hypotension and elevated lactate despite fluids). Initial infection is generally bacterial, with the most common origins being the respiratory, genitourinary, gastrointestinal, and dermatological systems or soft tissue. Patients can present with fever, tachycardia, confusion, and signs of the primary infection. The quick SOFA score may be used to identify patients with sepsis. Outcomes depend on early detection (obtaining blood cultures and measuring lactate), effective resuscitation measures (fluids and vasopressors), and early administration of antibiotics. Once the patient is stable, the diagnostic workup consists of identifying the source of infection and responsible pathogen in order to provide specific treatment and control the source of infection.

Definitions and criteria in this section apply to adult patients.

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

  • 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]

Other definitions of sepsis syndromes [1][2][3][4][5]

  • Systemic inflammatory response syndrome (SIRS criteria) : a constellation of physiological and immune-mediated reactions of the body to an infection or noninfectious insult (e.g., an acute inflammatory process or trauma) [1][2]
  • Sepsis: 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)
    • Progressive and potentially reversible failure in the physiologic function of several organs and/or systems [6]
    • The more organs that are affected, the greater the mortality risk
  • Bacteremia: the presence of bacteria in the bloodstream, confirmed on blood cultures [3]

Sequential organ failure assessment score (SOFA score) [1][7]

  • 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][8]
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

The SOFA score is not designed to diagnose sepsis.

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

References:[10][11][12][13][14][15][16]

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!

Diagnostic and treatment measures should be conducted simultaneously in a patient suspected of having sepsis. Success depends on early detection, early and effective resuscitation, and early antibiotic therapy.

Sepsis is a medical emergency and clinicians should have a high index of suspicion.

Approach

  1. Sepsis surveillance: Identify patients with potential sepsis.
  2. Initial clinical evaluation (should follow ABCDE approach)
  3. Initial resuscitation and ongoing clinical reassessment
  4. Supportive care

Initial resuscitation includes IV access, fluid resuscitation (and potentially vasopressor support), and broad-spectrum antibiotics.

2018 Surviving Sepsis Campaign recommendations for initial management [7]

  • Hour-1 bundle for sepsis

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

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 “Definitions” section for diagnostic criteria. [1][3][19]

Positive cultures are not mandatory for the diagnosis of sepsis.

Laboratory studies

In addition to serum lactate and blood cultures (at least two sets), the following laboratory studies should be obtained 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 [7][19][21]

  • Initial resuscitation: rapid crystalloid infusion of 30 mL/kg
    • Indications: sepsis and/or signs of hypoperfusion are present (e.g., hypotension, elevated lactate) [7]
    • Start immediately (within the first hour of presentation) and complete within 3 hours.
    • There is no benefit of colloids over crystalloids for most patients.
    • See also “IV fluids” for more details regarding fluid options.
  • Additional fluids: The decision to give additional fluids should be informed by fluid responsiveness [7]

6–10 L of IV fluids may be necessary during the first 24 hours. [3]

Clinical reassessment [7][19][20][22][23]

Hemodynamic and perfusion status should be continually reassessed to determine whether additional fluids are indicated (i.e., whether the patient is fluid responsive or not) or hemodynamic support should be escalated (i.e., whether vasopressor support is needed).

Clinical reassessment should be a continuous and iterative process throughout the resuscitation process.

Vasopressors for septic shock [7][19][20][22][23]

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

Respiratory support

Shock and metabolic acidosis are both associated with a high risk of peri-intubation mortality. [3][25]

Corticosteroids [7][26]

General recommendations

  • Broad-spectrum antibiotics are part of the hour-1 bundle and should be started early (ideally as soon as possible after blood cultures have been drawn).
  • Choice of empiric antimicrobial therapy should be guided by:
    • Source of infection
    • Local prevalence of common and resistant pathogens
    • Prior infections, immune status , and patient comorbidities
    • Presence of implanted devices (e.g., urinary catheter, central lines)
  • Therapy should be narrowed once the pathogen is identified. [3]
  • Control the source of infection as early as possible.

Antibiotic therapy for sepsis [7][22][26][27][28]

There is no consensus regarding empiric antibiotic regimens for patients with sepsis and septic shock, especially when the source of infection is unclear. The regimens mentioned here are examples commonly mentioned in the literature.

Evident source of infection [3]

Unclear source of infection [22][26][27][29]

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

Unknown risk factors

At risk for specific pathogens

Neutropenia

Antifungal therapy [7]

Source control [7][20]

The following is a list of noninfectious conditions that may mimic sepsis. [3][20]

  • Critical illness polyneuropathy
    • Definition: axonal injury, particularly to the motor neurons, as a sequela of sepsis and multiple organ dysfunction
    • Clinical features
      • Predominantly distal, symmetrical, flaccid paralysis of the extremities with muscle atrophy; may affect the diaphragm
      • Absent or reduced reflexes
      • Dysesthesias in a glove-and-stocking distribution may be present
      • Preservation of cranial nerve function
      • May be associated with critical illness myopathy : flaccid quadriparesis (proximal > distal); facial muscle weakness, sensation normal, tendon reflexes normal or ↑
    • Diagnosis: typical clinical features, sepsis, and electrophysiological evidence of motor and sensory neuropathy
    • Treatment: no specific treatment available, usually gradual spontaneous resolution (weeks to months)

Critical illness polyneuropathy is a common cause of prolonged weaning from mechanical ventilation in a patient with sepsis!
References:[31]

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

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