20. Sepsis and SIRS

1. Definition

Classical terms

• General purulent infection → systemic spread of a local infection
• Toxaemia → toxins in the blood without bacteria
• Bacteraemia → viable bacteria in the blood, may be transient
• Septicaemia → bacteria multiply in the blood with severe systemic illness; no metastatic abscesses
• Septicopyaemia (pyaemia) → septicaemia with metastatic abscesses (lung, liver, brain, kidney)

Systemic inflammatory response syndrome (SIRS)

• Systemic inflammation from any insult (infection, trauma, burns, pancreatitis)
• 2 or more criteria:
  1. Temperature > 38 °C or < 36 °C
  2. Heart rate > 90/min
  3. Respiratory rate > 20/min or PaCO2 < 32 mmHg
  4. White cell count > 12 × 10^9/L, < 4 × 10^9/L or > 10% immature forms
• Sepsis (old definition, Sepsis-2) → SIRS + infection

Sepsis-3 (2016)

• Sepsis → life-threatening organ dysfunction caused by a dysregulated host response to infection
• Organ dysfunction → rise in Sequential Organ Failure Assessment (SOFA) score ≥ 2
• Septic shock → sepsis needing vasopressors for mean arterial pressure (MAP) ≥ 65 mmHg, with lactate > 2 mmol/L despite adequate fluids
• Septic shock mortality → > 40%

Quick SOFA (qSOFA): bedside screen, 2 or more

1. Respiratory rate ≥ 22/min
2. Altered mental state (Glasgow Coma Scale < 15)
3. Systolic blood pressure ≤ 100 mmHg

2. Aetiology

• Surgical sources:
  • Abdominal → peritonitis, anastomotic leak, cholangitis, abscess
  • Soft tissue → necrotising fasciitis, phlegmon, infected wounds
  • Urinary tract → obstructed infected kidney
  • Lung → pneumonia
  • Lines and catheters
• Organisms → Gram-negative bacilli (E. coli, Klebsiella, Pseudomonas), Staphylococcus aureus, streptococci, anaerobes, fungi (Candida)
• Risk factors → age, diabetes, immunosuppression, cancer, recent surgery, invasive devices

3. Pathogenesis: mechanism of development

1. Bacterial products → endotoxin (lipopolysaccharide of Gram-negative bacteria), exotoxins, peptidoglycan
2. Recognised by immune cells (toll-like receptors)
3. Release of cytokines → tumour necrosis factor alpha (TNF-α), interleukin-1, interleukin-6
4. Endothelial activation:
   • Vasodilatation → nitric oxide
   • Capillary leak → hypovolaemia, tissue oedema
   • Microthrombosis → disseminated intravascular coagulation (DIC)
5. Impaired oxygen use by cells (mitochondrial dysfunction)
6. Compensatory anti-inflammatory response → immunosuppression, secondary infection
7. Multi-organ dysfunction syndrome (MODS)

4. Clinical picture

• Fever or hypothermia, rigors
• Tachycardia, tachypnoea
• Warm, flushed skin early → cold, mottled skin late
• Hypotension
• Confusion, agitation
• Oliguria
• Signs of the source → peritonitis, cellulitis, chest signs
• Organ dysfunction:
  • Lung → acute respiratory distress syndrome (ARDS)
  • Kidney → acute kidney injury
  • Liver → jaundice
  • Blood → thrombocytopenia, DIC
  • Gut → ileus, stress ulcer
  • Brain → encephalopathy
• Septicopyaemia → swinging fever with metastatic abscesses

5. Diagnosis

Laboratory

• Blood cultures → 2 sets before antibiotics
• Lactate
• Full blood count, CRP, procalcitonin
• Urea, creatinine, liver function, bilirubin
• Clotting, platelets, fibrinogen
• Arterial blood gas
• Cultures from the source → urine, sputum, pus, drain fluid

Imaging

• Chest X-ray
• Ultrasound → biliary tree, kidneys, collections
• CT → abdominal source, collections, leaks

6. Treatment: principles

Sepsis bundle within 1 h (Surviving Sepsis Campaign)

1. Measure lactate; repeat if > 2 mmol/L
2. Blood cultures before antibiotics
3. Broad-spectrum intravenous antibiotics within 1 h
4. Crystalloid 30 mL/kg for hypotension or lactate ≥ 4 mmol/L
5. Vasopressors (noradrenaline) for MAP < 65 mmHg despite fluids

Source control

• Drain, debride, remove → as soon as possible, within 6–12 h
• Drainage of abscess → percutaneous or surgical
• Laparotomy for peritonitis, leak
• Debridement of necrotising soft tissue infection
• Decompression of obstructed biliary or urinary tract
• Removal of infected lines and devices

Supportive care

• Oxygen, ventilation for ARDS
• Renal replacement therapy
• Hydrocortisone → shock not responding to vasopressors
• Glucose control (< 10 mmol/L)
• Thromboprophylaxis, stress ulcer prophylaxis
• Nutrition
• De-escalate antibiotics by culture results

7. Complications

• Septic shock
• ARDS
• Acute kidney injury
• DIC
• MODS
• Death