Key Facts

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute hypoxaemic respiratory failure caused by diffuse alveolar damage. The Berlin definition (2012) replaced the previous AECC criteria and stratifies ARDS into mild, moderate, and severe categories based on the PaO₂/FiO₂ ratio.

Epidemiology

ARDS affects approximately 3 per 100,000 population per year in the UK. Incidence increases with age and is higher in ICU populations (10-15% of ICU admissions). Overall mortality remains 35-46% despite advances in supportive care. COVID-19 significantly increased ARDS incidence during the 2020-2023 pandemic waves.

Aetiology

Causes are classified as pulmonary (direct) or extra-pulmonary (indirect):

• Pulmonary: pneumonia (most common — 60%), aspiration, inhalational injury, pulmonary contusion, drowning
• Extra-pulmonary: sepsis (most common indirect cause), pancreatitis, major trauma, massive transfusion (TRALI), burns, drug overdose, DIC

Pathophysiology

The pathological hallmark is diffuse alveolar damage (DAD) progressing through three phases:

1. Exudative phase (days 1-7): damage to alveolar epithelium and capillary endothelium → protein-rich oedema floods alveoli → hyaline membrane formation → surfactant dysfunction → atelectasis
2. Proliferative phase (days 7-21): type II pneumocyte proliferation, fibroblast migration, early fibrosis
3. Fibrotic phase (>3 weeks): extensive fibrosis, microcystic changes, persistent impaired gas exchange

The resulting ventilation-perfusion mismatch and intrapulmonary shunting cause refractory hypoxaemia. Reduced lung compliance necessitates higher ventilatory pressures, creating a risk of ventilator-induced lung injury (VILI).

Acute Presentation

• Acute onset dyspnoea and tachypnoea (usually within 72 hours of inciting event)
• Hypoxaemia refractory to supplemental oxygen
• Bilateral crackles on auscultation
• Tachycardia, use of accessory muscles, cyanosis
• Often features of the underlying cause (e.g. sepsis, pneumonia)

Progressive Features

• Worsening respiratory failure despite maximal oxygen therapy
• Multi-organ dysfunction (renal, hepatic, haematological)
• Haemodynamic instability requiring vasopressor support

Red Flags

• SpO₂ <90% despite FiO₂ >0.6
• Rapidly deteriorating PaO₂/FiO₂ ratio
• Rising lactate indicating tissue hypoxia
• Signs of barotrauma (surgical emphysema, pneumothorax)
• New organ dysfunction (oliguria, rising creatinine, coagulopathy)

Bedside

• ABG: hypoxaemia with calculated PaO₂/FiO₂ ratio (on PEEP ≥5 cmH₂O for Berlin criteria)
• CXR: bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules
• Echocardiography: to exclude cardiogenic pulmonary oedema (normal LV function, no raised LA pressure)
• ECG: exclude acute MI as cause of pulmonary oedema

Bloods

• FBC: neutrophilia (sepsis), eosinophilia (eosinophilic pneumonia)
• CRP/procalcitonin: infective markers
• U&Es, LFTs: organ dysfunction assessment
• Lactate: tissue perfusion
• BNP/NT-proBNP: to help distinguish from cardiogenic oedema
• Blood cultures: if sepsis suspected
• Coagulation screen: DIC assessment

Imaging

• CT thorax: bilateral ground-glass opacities and consolidation; helps exclude other pathology
• CT pulmonary angiogram: if PE suspected as precipitant

Special Tests

• Bronchoscopy + BAL: if atypical organisms, DAH, or eosinophilic pneumonia suspected
• Transpulmonary thermodilution (PiCCO): extravascular lung water measurement in ICU
• Lung ultrasound: B-lines, pleural irregularity, consolidation — increasingly used at bedside

Non-pharmacological

• Lung-protective ventilation: tidal volume 6 ml/kg IBW, plateau pressure <30 cmH₂O (ARDSNet ARMA trial)
• PEEP titration: higher PEEP (12-24 cmH₂O) in moderate-severe ARDS to maintain recruitment
• Prone positioning: ≥16 hours/day in severe ARDS (PaO₂/FiO₂ <150 on FiO₂ ≥0.6) — PROSEVA trial showed NNT of 6
• Conservative fluid management: target CVP <4 mmHg or EVLWI <10 ml/kg (FACTT trial)
• Permissive hypercapnia: accept pH >7.20 to maintain lung-protective volumes

Pharmacological

• Neuromuscular blockade: cisatracurium 15 mg bolus then 37.5 mg/hr infusion for 48 hours in early severe ARDS (ACURASYS trial — note ROSE trial did not replicate)
• Corticosteroids: dexamethasone 20 mg IV OD days 1-5, then 10 mg OD days 6-10 (DEXA-ARDS trial); methylprednisolone for persistent ARDS (Meduri protocol)
• Inhaled nitric oxide: 5-20 ppm as rescue therapy — improves oxygenation but no mortality benefit
• Treat underlying cause: antibiotics for sepsis/pneumonia, source control

Surgical/Interventional

• ECMO (veno-venous): for refractory hypoxaemia despite optimal ventilation — refer to ECMO centre (UK: 5 commissioned centres) per NICE IPGten and CESAR trial criteria
• Tracheostomy: if prolonged ventilation anticipated (usually day 10-14)

Referral Criteria

• Refer to ICU early if PaO₂/FiO₂ <200 despite high-flow oxygen
• Contact ECMO centre if PaO₂/FiO₂ <80 on optimal settings, or pH <7.20 with PaCO₂ >80 mmHg
• Early critical care outreach involvement

Overall hospital mortality 35-46% depending on severity: mild ~27%, moderate ~32%, severe ~45%. Survivors often have persistent functional limitation — 25% have reduced DLCO at 1 year. ICU-acquired weakness affects ~50% of prolonged ventilation survivors. Post-ARDS patients have increased rates of depression (30%), anxiety (40%), and PTSD (20%). Five-year mortality post-ARDS is approximately 50% in older populations.

Berlin Definition Severity Classification

Landmark Trials