Key Facts

Septic shock represents the most severe manifestation of sepsis, characterised by profound circulatory, cellular, and metabolic abnormalities that substantially increase mortality beyond sepsis alone. Prompt fluid resuscitation, early antibiotics, and vasopressor support are the cornerstones of management.

Epidemiology

• ~50,000 cases per year in the UK
• In-hospital mortality: 40–50% (despite modern intensive care)
• Accounts for 10% of ICU admissions
• 1-year mortality: ~60%
• Most common cause of death in non-cardiac ICU patients

Aetiology

• Same infectious sources as sepsis, but with more severe host response
• Gram-negative bacteraemia: higher incidence of shock vs Gram-positive
• Polymicrobial infections: higher mortality
• Fungal sepsis (Candida): increasing incidence in ICU, high mortality (~50%)
• Abdominal source: higher rate of shock than other sources

Pathophysiology

• Massive cytokine release → systemic vasodilation → distributive shock
• Endothelial glycocalyx disruption → capillary leak → tissue oedema and hypovolaemia
• Myocardial depression: cytokine-mediated (TNF-α, IL-1β) → reduced cardiac output
• Mitochondrial dysfunction → impaired oxygen utilisation despite adequate delivery (cytopathic hypoxia)
• Microvascular thrombosis → DIC → multi-organ failure
• Relative adrenal insufficiency → impaired vasopressor response
• Result: inadequate tissue oxygen delivery and utilisation → anaerobic metabolism → lactic acidosis → cell death

Early (Warm Shock)

• Flushed, warm peripheries (vasodilation)
• Bounding pulse, wide pulse pressure
• Tachycardia, tachypnoea
• Hypotension (SBP <90 or MAP <65)
• Confusion, agitation
• Fever or hypothermia

Late (Cold Shock)

• Cool, mottled, clamped peripheries
• Weak, thready pulse
• Profound hypotension
• Oliguria/anuria
• Reduced consciousness → obtundation

Multi-Organ Failure

• Respiratory: ARDS — bilateral infiltrates, PaO2/FiO2 <300
• Renal: AKI — oliguria, rising creatinine
• Hepatic: coagulopathy, jaundice, raised transaminases
• Haematological: DIC — thrombocytopenia, prolonged PT/APTT
• Neurological: septic encephalopathy — confusion, delirium, coma

Red Flags

• MAP <65 despite 30 ml/kg fluid resuscitation
• Lactate >4 mmol/L (or rising despite treatment)
• Vasopressor requirement escalating rapidly
• PaO2/FiO2 <200 (severe ARDS)
• Anuria >6 hours
• Mottled skin, prolonged capillary refill >5 seconds

Bedside

• Arterial blood gas: pH, lactate, PaO2/FiO2 ratio — serial measurements
• NEWS2 score: will be high (≥7)
• Blood glucose: stress hyperglycaemia or hypoglycaemia
• ECG: arrhythmias, new ischaemia
• Bladder catheter: hourly urine output monitoring

Bloods

• Blood cultures: before antibiotics (peripheral + central line)
• FBC: leucocytosis/leucopenia, thrombocytopenia
• U&Es: AKI
• LFTs: hepatic dysfunction
• Lactate: serial (every 2–4 hours) — target clearance >20% in 6 hours
• Coagulation: PT, APTT, fibrinogen, D-dimer (DIC screen)
• CRP, procalcitonin: inflammation
• Cortisol: if adrenal insufficiency suspected

Imaging

• CXR: ARDS, pneumonia
• CT with contrast: source identification (abdominal collection, perforation)
• Echocardiography: assess cardiac function, guide fluid management

Special Tests

• Central venous pressure (CVP): guide fluid resuscitation (target 8–12 mmHg)
• ScvO2 (central venous oxygen saturation): <70% suggests inadequate oxygen delivery
• Point-of-care USS: IVC diameter for volume assessment, lung USS for ARDS
• Cardiac output monitoring: PiCCO, LiDCO in complex cases

Non-pharmacological

• ICU admission: mandatory for vasopressor therapy
• Invasive monitoring: arterial line (continuous BP), CVC (for vasopressors and CVP)
• Lung-protective ventilation: if intubated — tidal volume 6 ml/kg IBW, plateau pressure <30 cmH2O
• Prone positioning: for severe ARDS (PaO2/FiO2 <150) — PROSEVA trial
• Blood glucose control: target 6–10 mmol/L (NICE-SUGAR trial)
• VTE prophylaxis: LMWH unless contraindicated
• Source control within 6–12 hours: drain collections, remove infected devices, debride necrotic tissue

Pharmacological

Antibiotics:

• Administer within 1 hour — broad-spectrum empirical then de-escalate
• Same principles as sepsis but with broader cover initially

Fluid resuscitation:

• 30 ml/kg crystalloid (0.9% NaCl or balanced solution e.g. Plasmalyte) within 3 hours
• Reassess with dynamic measures (pulse pressure variation, passive leg raise)
• Avoid fluid overload: positive fluid balance associated with worse outcomes
• CLASSIC trial: restrictive vs liberal fluids in septic shock — restrictive strategy appears safe

Vasopressors:

• Noradrenaline: first-line, 0.05–0.5 mcg/kg/min, titrate to MAP ≥65
• Vasopressin: 0.03 units/min as second agent (VASST trial)
• Adrenaline: third-line if above insufficient
• Dobutamine: if evidence of myocardial dysfunction (low CO despite adequate filling)

Corticosteroids:

• Hydrocortisone 50mg IV QDS (200mg/day) if shock refractory to fluids + noradrenaline ≥0.25 mcg/kg/min
• APROCCHSS trial: hydrocortisone + fludrocortisone reduced 90-day mortality
• ADRENAL trial: faster shock reversal but no significant mortality difference

Organ support:

• RRT/CRRT: for AKI with standard indications
• Stress ulcer prophylaxis: IV PPI (omeprazole 40mg) — SUP-ICU trial suggests may not be needed in all patients

Surgical/Interventional

• Source control: essential within 6–12 hours
• Interventional radiology: percutaneous drainage of collections
• ECMO: in refractory ARDS or cardiac failure (case-by-case basis)

Referral Criteria

• All patients require ICU/critical care
• Surgical/IR input for source control
• Microbiology for complex infections
• Renal team if RRT needed

• In-hospital mortality: 40–50%
• ICU mortality: 30–40%
• 90-day mortality: ~45–55%
• 1-year mortality: ~60%
• Lactate >4 mmol/L: mortality >40%
• Need for ≥2 vasopressors: mortality >50%
• New-onset ARDS: mortality increases to ~50–60%
• Survivors: ~30% develop new functional disability; ~25% develop PTSD/depression
• Long-term cognitive impairment in ~30–40% of sepsis survivors
• Re-hospitalisation within 90 days: ~40%

SOFA Score Components

Key Landmark Trials in Septic Shock