• Clinical science

Sepsis

Summary

Sepsis is an acute life-threatening condition characterized by organ dysfunction due to a dysregulated immune response to infection. The previously widely used term “systemic inflammatory response syndrome” (SIRS) is now considered outdated because its criteria were too simplified. Initial infection is generally bacterial and commonly of respiratory, genitourinary, gastrointestinal, dermatological, or soft tissue origin. Risk factors include immunocompromise, chronic comorbidities (e.g., diabetes mellitus), young or old age, and lengthy or invasive medical care. Patients may present with fever, tachycardia, confusion, and signs of the primary infection. Organ dysfunction is determined using a sequential organ failure assessment (SOFA) score that considers multiple parameters, but may be quickly evaluated and assumed if two of the following findings are present: tachypnea, hypotension, and altered mental status. Diagnostic workup focuses on determining the responsible pathogen via cultures and identifying the source of infection (e.g., via imaging, ECG, lumbar puncture). Laboratory findings are largely nonspecific. Prompt, aggressive treatment is vital to survival and consists of resuscitation, empiric antibiotic therapy, and control of the infectious source.

Etiology

References:[1][2][3][4][5][6][7]

Classification

2015 criteria and SOFA classification (The third international consensus definitions for sepsis and septic shock, Sepsis-3)

  • Sepsis: acute and life-threatening organ dysfunction due to abnormal host response to infection
  • Septic shock consists of the following parameters:
    • Sepsis +
    • Significant circulatory, metabolic, and cellular abnormalities +
    • Requiring vasopressor therapy to maintain a mean blood pressure of ≥ 65 mmHg and presence of increased lactate levels > 2 mmol/L (18 mg/dL) in the absence of hypovolemia
  • The term “severe sepsis” is no longer used
  • Quick SOFA criteria (qSOFA): to predict mortality in adult patients with suspected infection outside of the ICU (e.g., ward, emergency unit, or prior to hospitalization)

Sequential Organ Failure Assessment score (SOFA score) [8][9]

Organ dysfunction and score 0 1 2 3 4

Respiration

PaO2/FiO2 (mmHg)

≥ 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 mmHg

MAP

< 70 mmHg

Dopamine < 5,

or dobutamine

(any dose)*

Dopamine > 5.1–15, or

epinephrine ≤ 0.1, or

norepinephrine ≤ 0.1*

Dopamine > 15, or

epinephrine > 0.1, or

norepinephrine > 0.1*

Central nervous system

Glasgow Coma Scale

15 13–14 10–12 6–9 < 6

Renal system

Creatinine (mg/dL) or urine output (mL/d)

< 1.2 1.2–1.9 2.0–3.4

3.5–4.9

or < 500

> 5.0

or < 200

Abbreviations: PaO2 = partial pressure of oxygen; FiO2 = fraction of inspired oxygen; MAP = mean arterial blood pressure

* Catecholamine doses are administered as μg/kg /min for ≥ 1 hour


References:[3][10][8][11][12][13]

Pathophysiology

An adequate immune response requires a balance between proinflammatory (anti-infectious) and anti-inflammatory signals!

Clinical features

Origin Example of infection Characteristic features
CNS Meningitis
  • Meningism, altered mental status, photophobia
Respiratory Pneumonia
Cardiac Endocarditis
Abdominal Any cause of acute abdomen (e.g., appendicitis)
  • Abdominal pain, peritonism, possible distension, vomiting
Pelvic Pelvic inflammatory disease
Urinary Pyelonephritis, Urosepsis
  • Dysuria, frequency, flank pain
Bone Osteomyelitis
  • Local pain (possibly exacerbated with movement), tenderness, warmth, erythema
Soft tissue Abscess
  • Local warmth, erythema, tenderness with firm or fluctuant swelling (possibly indurated or draining pus)
  • Possible foreign body at the site of inflammation

References:[1][2][14]

Diagnostics

References:[15][1][2][3][12][16]

Treatment

In addition to immediate resuscitation and empiric therapy, the infectious focus must be identified and treated!
References:[15][1][2][17][18]

Complications

  • Critical illness polyneuropathy
    • Definition: axonal injury, particularly to the motor neurons, as a sequela of sepsis and multiple organ dysfunction
    • Clinical features
    • Diagnosis: typical clinical features, sepsis, and electrophysiological evidence of motor and sensory neuropathy
      • Electromyography (EMG): spontaneous activity (e.g., fibrillations)
      • Nerve conduction studies: normal velocity, reduced amplitude
    • 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:[19]

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