Sepsis is a life-threatening condition caused by a dysregulated immune response to pathogens or their toxins in blood or tissue. The organisms can be bacteria, viruses or fungi, while toxins may include endotoxin (LPS) or exotoxins.
Sepsis may range from mild e.g. cellulitis to severe e.g. septic shock +/- organ dysfunction. It exists as a continuum: Infection → systemic Inflammatory Response (SIRS) → sepsis → severe sepsis or organ dysfunction → septic shock → multi-organ dysfunction syndrome (MODS)
The overall mortality from sepsis is 25%
Definition of terms
| Term | Definition |
|---|---|
| Septic shock | Persistent hypotension despite fluid resuscitation, requiring vasopressors to keep MAP ≥ 65 mmHg, and a serum lactate level of > 2 mmol/l |
| Bacteraemia | Presence of bacteria in the blood stream |
| Septicaemia | Presence of large numbers of actively dividing bacteria in the blood stream resulting in systemic inflammatory response (SIRS) leading to organ dysfunciton |
| Pyaemia | Septicaemia caused by pus-forming bacteria e.g. staphylococci |
| Systemic inflamamtory response syndrome (SIRS) | Systemic inflammatory response characterized by two or more of: hyperthermia, tachycardia, tachypnoea, neutrophilia or neutropaenia. Mediated pro-inflamamtory by IL-1, TNF-a, IL-6, IL-8, IF-Y which activate coagulation cascade (microvascular thrombosis), complement cascade (vascular permiability), and endothelial damage. |
| Counter inflammatory response syndrome (CARS) | Systemic response that antagonizes SIRS through the action of IL-4 and IL-10. |
Sepsis-3 now defines sepsis as suspected or confirmed infection plus organ dysfunction, represented by an increase in SOFA score ≥ 2 points
Sequential Organ Failure Assessment (SOFA) score: evaluates 6 organ systems (each scored from 0 – 4). A score ≥ 2 points suggests significant organ dysfunction.
| Organ System | Parameter |
|---|---|
| Respiratory | PaO₂/FiO₂ ratio |
| Coagulation | Platelet count |
| Liver | Bilirubin |
| Cardiovascular | MAP and vasopressor requirement |
| CNS | Glasgow Coma Scale |
| Renal | Creatinine or urine output |
Detailed SOFA Score
| System | Score 0 | Score 1 | Score 2 | Score 3 | Score 4 |
|---|---|---|---|---|---|
| PaO2 /FI O2 | >400 | <400 | <300 | <200 | <100 |
| Platelets x103microlitres | >150 | <150 | <100 | <50 | <20 |
| Bilirubin µmol/L | 20 | 20-32 | 33-101 | 102-204 | >204 |
| Cardiovascular | MAP >70mmHg | MAP 70mmHg | Dopamine <5 or dobutamine (any dose) | Dopamine 5.1-15or epinephrine 0.1or norepinephrine 0.1 | Dopamine >15 orepinephrine >0.1or norepinephrine >0.1 |
| GCS | 15 | 13-14 | 10-12 | 6-9 | <6 |
| Creatinine µmol/L | <110 | 110-170 | 171-299 | 300-440 | >440 |
| Urine output ml/day | >500 | >500 | >500 | <500 | <200 |
Quick Sequential Organ Failure Assessment (qSOFA): a simplified bedside screening tool outisde the ICU to rapidly identify patients who need urgent evaluation. A qSOFA ≥ 2 is associated with poor outcomes.
- Respiratory rate > 22/min
- Altered mentation (GCS < 15)
- Systolic blood pressure < 100 mmHg
- Common causes of systemic inflammatory response syndrome (SIRS)
- Perforated viscus with peritonitis
- Fulminant colitis
- Multiple trauma
- Acute pancreatitis
- Burns
- Massive blood transfusion
- Aspiration pneumonia
- Pulmonary embolism
- Ischaemia reperfusion injury
- Risk factors
- Diabetes
- Cancer
- Chronic kidney disease
- Liver disease
- Immunosuppression
- Steroid use
- Burns
- Trauma
- Indwelling catheters
- Extremes of age
- Pathophysiology
- Pathogen virulence → survival, replication, and dissemination within the body
- Pathogen-associated molecular patterns (PAMPs) are recognized by Toll-like receptors (TLRs) → immune activation and release of pro-inflammatory cytokines
- Immune activation by pathogens → Systemic inflammatory response syndrome (SIRS)
- Endothelial injury → capillary leak → oedema and hypovolemia
- Vasodilation → low systemic vascular resistance and hypotension
- Microvascular thrombosis → worsened tissue perfusion
- Tissue hypoxia → lactate accumulates
- Immunoparalysis
- Compensatory anti-inflammatory response (CARS) suppresses the immune system making septic patients susceptible to secondary infections
- Organ dysfunction
- Lungs → acute respiratory distress syndrome (ARDS)
- Kidneys → acute kidney injury (AKI)
- Brain → encephalopathy
- Liver → hepatic dysfunction
- Cardiovascular system → shock
- Signs and sysmptoms
- Early
- Fever or hypothermia
- Tachycardia
- Tachypnoea
- Leukocytosis or leukopaenia
- Severe
- Altered mental status
- Oliguria
- Hypoxia
- Cyanosis
- Elevated lactate
- Warm septic shock (early)
- Warm extremities
- Bounding pulses
- Flash capillary refill
- Tachycardia
- Cold septic shock (late)
- Hypotension
- Cool extremities
- Delayed capillary refill time
- Weak pulses
- Early
- Investigations
- Complete blood count and peripheral blood film
- Leukocytosis or leukopenia
- Thrombocytopaenia
- Bandemia
- CRP and procalcitonin
- Elevated
- Lactate
- 2 mmol/L
- 4 mmol/L correlates with worse tissue hypoperfusion and mortality
- Coagulation panel
- Elevated INR
- Elevated aPTT
- Liver function test
- Hyperbilirubinaemia
- Renal function test
- Blood gas analysis
- Blood cultures
- Urinalysis
- Chest X-ray
- CT imaging if indicated
- Complete blood count and peripheral blood film
- Initial treatment
- The sepsis six bundle should be administered within 1 hour
- Administer oxygen
- Aim to keep saturation > 94% or 88-92% in COPD
- Blood cultures
- Broad spectrum antibiotics
- Within 1 hour
- Target the likely organism
- Intravenous fluid challenge
- 30 ml/kg crystalloid bolus or 500 ml crystalloid over less than 15 minutes
- For hypotension or lactate > 4 mmol/L
- Vasopressors if hypotension persists after fluids
- Target MAP ≥ 65 mmHg
- Measure serum lactate
- Measure urine output hourly
- Further treatment
- Source control
- Drain abscesses
- Remove infected lines or devices
- Debride necrotic tissues
- Organ support
- Mechanical ventilation for ARDS
- Dialysis for renal failure
- Nutritional support
- DVT prophylaxis
- Stress ulcer prophylaxis
- Source control
- Complications
- Acute respiratory distress syndrome
- Disseminateed intravascular coagulation
- Acute kidney injury
- Liver failure
- Mesenteric ischaemia
- Myocardial dysfunction
- Multi-organ failure
Surviving Sepsis Bundles
| Bundle Stage | Intervention | Key Details / Targets | Purpose |
|---|---|---|---|
| Initial / Hour-1 Bundle | Measure lactate | Lactate >2 mmol/L suggests hypoperfusion | Assess severity and prognosis |
| Obtain blood cultures | At least 2 sets before antibiotics if possible | Identify causative organism | |
| Start broad-spectrum antibiotics | Ideally within 1 hour | Reduce mortality from delayed treatment | |
| Fluid resuscitation | 30 ml/kg crystalloid | Restore intravascular volume and tissue perfusion | |
| Vasopressors if hypotensive after fluids | First-line: norepinephrine | Maintain organ perfusion | |
| Blood pressure target | MAP > 65 mmHg | Adequate tissue perfusion | |
| Reassessment Bundle | Repeat lactate | If initially elevated | Monitor response to therapy |
| Reassess perfusion | HR, BP, urine output, capillary refill, mental state | Guide ongoing management | |
| 24-Hour Management Bundle | Source control | Drain abscess, remove infected devices, surgery if needed | Eliminate infection source |
| Lung-protective ventilation | 6 ml/kg tidal volume | Reduce ventilator-induced lung injury in Acute respiratory distress syndrome | |
| Glucose control | Maintain glucose <180 mg/dL | Prevent complications of hyperglycemia | |
| Corticosteroids | Hydrocortisone for refractory shock | Improve vasopressor responsiveness | |
| DVT prophylaxis | Anticoagulation/mechanical methods | Prevent thromboembolism | |
| Stress ulcer prophylaxis | PPIs/H2 blockers if indicated | Prevent GI bleeding | |
| Early enteral feeding | Prefer enteral over parenteral nutrition | Preserve gut integrity and reduce bacterial translocation |