Key Facts

Sepsis is a medical emergency requiring the same urgency of response as cardiac arrest or major trauma. The UK Sepsis Trust estimates that early recognition and treatment could save 14,000 lives per year in the UK. Structured assessment tools and protocolised care pathways have significantly improved outcomes.

Epidemiology

Sepsis affects approximately 48,000 people per year in England, with approximately 26,000 deaths attributed to sepsis. It accounts for approximately 2% of all hospital admissions. Global sepsis incidence is approximately 49 million cases per year with 11 million deaths (Lancet 2020). Sepsis mortality has improved from ~50% to ~25-30% over the past 20 years.

Aetiology

Common sources of infection:

• Respiratory (pneumonia) — most common (~40%)
• Urinary tract (~20%)
• Abdominal (peritonitis, cholangitis, diverticulitis) (~15%)
• Skin/soft tissue (cellulitis, necrotising fasciitis) (~10%)
• Line-related/healthcare-associated (~10%)
• Unknown source (~5%)

Common organisms: Gram-negative (E. coli, Klebsiella, Pseudomonas), Gram-positive (S. aureus, S. pneumoniae, Streptococcus spp.); polymicrobial in abdominal sepsis

Pathophysiology

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis-3 definition). The pathophysiology involves:

• Immune dysregulation: Pro-inflammatory (TNF-α, IL-1, IL-6) and anti-inflammatory mediators causing tissue damage AND immunosuppression simultaneously
• Endothelial dysfunction: Increased vascular permeability, microvascular thrombosis, vasodilation
• Organ dysfunction: Occurs through microcirculatory failure, mitochondrial dysfunction, and cellular injury
• Septic shock: Sepsis with persistent hypotension requiring vasopressors AND lactate >2 mmol/L despite adequate fluid resuscitation

Sepsis Screening (Red Flag Criteria — NICE NG51)

High risk (any one of — amber/red flag):

• Systolic BP ≤90 mmHg or drop >40 from baseline
• Heart rate >130/min
• Respiratory rate ≥25/min
• Temperature <36°C
• New confusion or altered mental state
• Lactate >2 mmol/L
• Non-blanching rash (meningococcal/purpura fulminans)
• Urine output <0.5 mL/kg/hr

Septic Shock

• Persistent hypotension despite adequate fluid resuscitation (≥30 mL/kg crystalloid)
• Requiring vasopressors to maintain MAP ≥65 mmHg
• Lactate >2 mmol/L despite resuscitation
• Warm peripheries (early/hyperdynamic) → cool, mottled (late/hypodynamic)

Red Flags

• NEWS2 ≥7 or single parameter 3 — trigger urgent review
• Lactate >4 mmol/L — high mortality, ICU referral
• Purpuric/non-blanching rash — consider meningococcal sepsis
• Neutropenic sepsis (WCC <0.5 × 10⁹/L) — immediate IV antibiotics per local protocol
• Immunosuppressed patients — low threshold for sepsis screening

Bedside

• NEWS2 score: Trigger for sepsis screening
• Lactate (VBG/ABG): Immediate — guide severity and resuscitation response
• Blood glucose: Hypoglycaemia or hyperglycaemia
• Urine output: Catheterise — target >0.5 mL/kg/hr
• Point-of-care USS: Assess fluid status, cardiac function, source (e.g., hydronephrosis, ascites)

Bloods

• Blood cultures (×2 sets): Before antibiotics — aerobic and anaerobic bottles from separate sites
• FBC: WCC (leucocytosis or leucopenia), platelets (DIC)
• U&Es: AKI (rising creatinine)
• LFTs, bilirubin: Hepatic dysfunction
• Coagulation + fibrinogen: DIC screening
• CRP: Inflammatory marker (non-specific)
• Procalcitonin: More specific for bacterial infection; guides antibiotic duration

Imaging

• CXR: Pneumonia source
• CT abdomen: Intra-abdominal source (perforation, abscess, cholangitis)
• Renal USS: Obstructed infected system (pyonephrosis)

Special Tests

• Urine MC&S: UTI source
• Wound swab/tissue culture: Soft tissue source
• Lumbar puncture: If meningitis suspected (after CT if raised ICP concerns)
• SOFA score: Quantifies organ dysfunction (≥2 increase defines sepsis)

Non-pharmacological

• Sepsis 6 within 1 hour: Give O2, Give IV fluids, Give IV antibiotics, Take blood cultures, Measure lactate, Measure urine output
• Source control: Essential — drain abscess, remove infected device, debride wound, relieve obstruction

Pharmacological

Fluid resuscitation:

• IV crystalloid 500mL bolus (20mL/kg in children); assess response; repeat up to 30mL/kg in first 3 hours
• Reassess after each bolus — avoid fluid overload

Antibiotics (within 1 hour):

• Empiric broad-spectrum: Per local trust guidelines (e.g., piperacillin-tazobactam 4.5g IV TDS or meropenem 1g IV TDS for severe/source unknown)
• Community-acquired pneumonia: Co-amoxiclav 1.2g IV + clarithromycin 500mg IV
• UTI: Co-amoxiclav 1.2g IV or gentamicin per local protocol
• Neutropenic sepsis: Piperacillin-tazobactam 4.5g IV TDS (per NICE NG151)
• Narrow spectrum based on culture results; review at 48-72h

Vasopressors (if fluid-resistant hypotension):

• Noradrenaline: First-line — 0.05-1 mcg/kg/min (via central line) to target MAP ≥65 mmHg
• Vasopressin 0.03 units/min: Adjunct if noradrenaline alone insufficient
• Hydrocortisone 200mg/day: If vasopressor-dependent despite adequate fluids (ADRENAL trial — no mortality benefit but faster shock resolution)

Surgical/Interventional

• Source control: Priority — interventional radiology drainage, laparotomy, nephrostomy, debridement
• Renal replacement therapy: For AKI with refractory hyperkalaemia, acidosis, or fluid overload

Referral Criteria

• NEWS2 ≥7 or lactate >4 — ICU referral
• Vasopressor-dependent hypotension — ICU admission
• Neutropenic sepsis — haematology and infectious diseases
• Failure to respond to initial resuscitation — senior review and ICU

• Sepsis mortality: ~25-30% overall; septic shock ~30-40%
• Each hour delay in antibiotics increases mortality by ~7.6%
• Sepsis 6 compliance: Reduces mortality by approximately 20%
• Lactate clearance >10% at 6 hours: Associated with improved survival
• Post-sepsis syndrome: ~40% of survivors have physical/psychological sequelae at 1 year
• 30-day readmission: ~20% — often due to recurrent infection or deconditioning

Sepsis Six Bundle

SOFA Score (Sequential Organ Failure Assessment)

Increase ≥2 from baseline = sepsis (Sepsis-3 definition).

Key Sepsis Trials