ARDS: Berlin definition, lung-protective ventilation, proning, and ECMO

Also known as ARDS · Acute respiratory distress syndrome · Berlin definition · Lung-protective ventilation · Proning · PROSEVA

Acute Respiratory Distress Syndrome (ARDS) = acute diffuse inflammatory lung injury → increased pulmonary vascular permeability → bilateral opacities + refractory hypoxaemia (PaO2/FiO2 ≤300 with PEEP ≥5). BERLIN DEFINITION (2012): timing (within 1 week of insult), chest imaging (bilateral opacities — not fully explained by effusions/atelectasis/nodules), origin of oedema (NOT heart failure or fluid overload — echo to exclude), hypoxaemia severity: MILD (PaO2/FiO2 200-300), MODERATE (100-200), SEVERE (≤100). CAUSES: direct (pneumonia, aspiration, inhalation, near-drowning, trauma) or indirect (sepsis, shock, pancreatitis, transfusion [TRALI], burns, drug). MANAGEMENT: (1) TREAT CAUSE (antibiotics, source control). (2) LUNG-PROTECTIVE VENTILATION (Vt 6 mL/kg IBW, plateau <30 cmH2O, PEEP titrated — ARDSNet 2000 — reduced mortality). (3) PRONING (≥16h/day for MODERATE-SEVERE — PROSEVA 2013 — reduced mortality 16% absolute). (4) HFNC (FLORALI — may avoid intubation). (5) ECMO (VV-ECMO for refractory — EOLIA/CESAR — rescue). (6) FLUID CONSERVATIVE (FACTT — less fluid - better oxygenation + ventilator days). (7) NEUROMUSCULAR BLOCKADE (ACURASYS — cisatracurium 48h for severe — reduces mortality — ROSE questioned — controversial). (8) STEROIDS (controversial — DEXA-ARDS — dexamethasone for moderate-severe — emerging). MORTALITY: mild 27%, moderate 32%, severe 45%.

high25 referencesUpdated 26 July 202622 min readSource-verified · Sept 2026

Checked against its sources on 11 Sept 2026

Practise this topic

8 MCQs

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Meet the patient

A 64-year-old man (height 178 cm) is admitted to ICU 36 hours after a perforated appendix with septic shock. He is intubated, volume control Vt 450 mL (6.1 mL/kg PBW), PEEP 10, FiO2 0.8. PaO2 76, PaCO2 42, pH 7.30. Bilateral infiltrates on the chest X-ray; echo shows a normal LV. The trainee says "his P/F is 95 — moderate ARDS — we should paralyse and prone." The consultant asks him first to apply the Berlin definition and calculate PBW.^[1]

The exam question. How do you apply the Berlin definition, set lung-protective ventilation, and run the management ladder (low Vt, prone, conservative fluids, steroids, ECMO)? The two interventions with proven mortality benefit are low Vt (ARDSNet 2000 - 22 per cent relative reduction) and prone ≥16 h/day (PROSEVA 2013 - ~50 per cent relative reduction).^[2]^[3]

ARDS severity (Berlin definition)

Feature	Mild	Moderate	Severe
PaO2/FiO2 (with PEEP ≥5)	200-300	100-200	≤100
Chest imaging	Bilateral opacities	Bilateral opacities	Bilateral opacities
Mortality	27%	32%	45%
Ventilator days (median)	5	7	9
Proning indicated?	No (PaO2/FiO2 <150)	If <150	YES (PROSEVA)
ECMO considered?	No	If refractory	If refractory (PaO2/FiO2 <80)

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Management of moderate-severe ARDS

Diagnose (Berlin) and treat the cause. The Berlin criteria are: timing within 1 week of a known clinical insult; bilateral opacities on chest imaging, not fully explained by effusions, atelectasis or nodules; origin of oedema — respiratory failure not fully explained by cardiac failure or fluid overload (objective assessment — echo — is needed if there is no clear risk factor for ARDS); and hypoxaemia graded mild (PaO2/FiO2 200-300 with PEEP/CPAP ≥5), moderate (100-200) or severe (≤100). Direct (pulmonary) causes are pneumonia [most common], aspiration, inhalation injury, near-drowning and pulmonary contusion; indirect (extrapulmonary) causes are sepsis, severe shock, pancreatitis, massive transfusion (TRALI), burns and drug reaction. Treat the cause: antibiotics (pneumonia/sepsis), source control (drain abscess), stop the offending drug/transfusion, treat pancreatitis. ARDS won't resolve until the cause is treated.
Lung-protective ventilation (ARDSNet — mortality reduction). Tidal volume 6 mL/kg predicted (ideal) body weight, not actual — calculated by height and sex (male = 50 + 0.91 × [height cm − 152.4]; female = 45.5 + 0.91 × [height cm − 152.4]). Plateau pressure ≤30 cmH2O, measured with an inspiratory pause; if >30, reduce Vt [to 4 mL/kg if needed] — the lung is injured and small ('baby lung'), and high pressure causes volutrauma and barotrauma. PEEP is titrated by the ARDSNet PEEP/FiO2 table to maintain alveolar recruitment and reduce atelectrauma. Respiratory rate 6-35 to maintain minute ventilation, with a pH target >7.25 and hypercapnia accepted (permissive). ARDSNet (2000, NEJM) compared Vt 6 vs 12 mL/kg: 6 mL/kg reduced mortality 22% (31% vs 40%), and lung-protective ventilation is standard. Driving pressure (ΔP = plateau − PEEP) <15 cmH2O (Amato 2015 — best predictor of mortality; lower is better); if ΔP is high despite low Vt, reduce Vt further and increase PEEP.
PEEP optimisation. The goal is to maintain alveolar recruitment (preventing cyclic opening-closing, which is atelectrauma), improve oxygenation and reduce lung injury. The ARDSNet PEEP/FiO2 table sets higher PEEP for higher FiO2 (more hypoxaemic), to recruit and maintain alveoli. Higher vs lower PEEP: ART (2017, JAMA) found higher PEEP (recruitment manoeuvres plus high PEEP) worse — more mortality, barotrauma; EXPRESS (2008, JAMA) found a moderate-PEEP benefit, but not aggressive.^[25] Current practice is moderate PEEP by the PEEP/FiO2 table, not aggressive recruitment manoeuvres (ART harm). Where oesophageal pressure (oPes) is available, measure transpulmonary pressure (plateau − oPes) and titrate PEEP to keep transpulmonary pressure positive (avoiding lung collapse).
Prone positioning (PROSEVA — mortality reduction). Indicated for moderate-severe ARDS (PaO2/FiO2 <150) despite adequate ventilation (Vt 6 mL/kg plus PEEP). PROSEVA (2013, NEJM): prone ≥16 hours/day for PaO2/FiO2 <150 reduced mortality (28-day 16.0% vs 32.8% — 16.8% absolute reduction — NNT 6; 90-day 23.6% vs 41.0%). Proning reduces shunt (the dorsal lung [usually collapsed in supine] is recruited when prone — gravity redistributes perfusion), reduces ventilation-perfusion mismatch (more uniform ventilation when prone), reduces lung strain (more uniform inflation — less overdistension of ventral lung — less atelectrauma of dorsal lung) and facilitates secretion clearance (drainage from dependent regions). Technique: turning prone (face down) requires 4-6 staff (turning, airway, lines, monitoring); maintain ≥16 hours/day (usually 16-20h prone plus 4-8h supine for care/procedures); pad pressure points (face, chest, pelvis, knees — prevent pressure injuries); monitor the ETT (don't dislodge during turning), SpO2 (may transiently drop during the turn — then improve) and lines/tubes (secure — check all). Relative contraindications: spinal instability, severe pelvic fractures, recent abdominal surgery, pregnancy, raised ICP (relative), haemodynamic instability. Early proning (within 36h of moderate-severe ARDS) is better than late (PROSEVA enrolled within 24-48h).
HFNC (high-flow nasal cannula) — may avoid intubation. A trial of HFNC is indicated for moderate hypoxaemic respiratory failure (PaO2/FiO2 200-300), before intubation. High flow (up to 60 L/min) washes out dead space (reducing CO2 rebreathing); there is a PEEP effect (low-level positive pressure 3-5 cmH2O, maintaining alveolar recruitment); work of breathing is reduced (heated humidified gas means less respiratory effort); and inspiratory resistance is reduced (the nasal cannula gas flow matches the patient's inspiratory demand). FLORALI (2015, NEJM) compared HFNC vs standard O2 (face mask) vs NIV in acute hypoxaemic respiratory failure (P/F ≤300): HFNC showed a trend to a lower intubation rate (38% vs 47% vs 50%) and lower 90-day mortality (significant). ROX index (SpO2/FiO2 / RR): reassess after 12h of HFNC — ROX <4.88 means a higher risk of needing intubation; ≥4.88 is likely to succeed (continue HFNC). Intubate for HFNC failure: worsening hypoxaemia (SpO2 <90% despite FiO2 100%), rising RR (>35-40), exertion/exhaustion (accessory muscle use, paradoxical breathing), altered consciousness, haemodynamic instability, or ROX <4.88 at 12h. If the trial is not improving within 1-2h, intubate (don't delay — delayed intubation is worse than early).
Neuromuscular blockade (NMB). ACURASYS (2010, NEJM): cisatracurium 48h for severe ARDS (PaO2/FiO2 <150) reduced mortality, adjusted hazard ratio 0.68 (especially in PaO2/FiO2 <120). ROSE (2019, NEJM): cisatracurium 48h vs placebo (light sedation) showed no benefit (no difference in mortality) — but ROSE used lighter sedation and a different protocol, so this is controversial. Current practice is NMB for severe ARDS (PaO2/FiO2 <120) with high driving pressure / asynchrony, as a short course (48h), but not routinely for all (ROSE questioned): use it if there is ventilator asynchrony or the patient is uncontrolled (high driving pressure despite Vt 6 plus sedation). Avoid prolonged NMB (>48h — ICU-acquired weakness).
Steroids. DEXA-ARDS (2020, Lancet Respir Med): dexamethasone 20 mg/day x5 days then 10 mg/day x5 days for moderate-severe ARDS reduced mortality (21% vs 36% at 60 days) with more ventilator-free days. Current practice is to consider dexamethasone for moderate-severe ARDS (especially from COVID-19 — RECOVERY — dexamethasone reduced mortality in ventilated COVID). This is controversial and not universally adopted: some guidelines recommend it (DEXA-ARDS and RECOVERY support), others are cautious (historical methylprednisolone trials mixed).
ECMO (VV-ECMO). Indicated for refractory severe ARDS (PaO2/FiO2 <80 despite optimisation — lung-protective ventilation, proning and PEEP) or severe hypercapnia with pH <7.2. CESAR (2009, Lancet): referral to an ECMO centre reduced mortality (37% vs 53% in conventional). EOLIA (2018, NEJM): VV-ECMO vs conventional for very severe ARDS (PaO2/FiO2 <50) was stopped early for futility (no difference in the primary outcome [mortality at 60d]) — but Bayesian re-analysis suggested possible benefit. Current practice is ECMO as rescue for refractory disease (not routine): refer to an ECMO centre, as a bridge to recovery (the lungs heal). Complications: bleeding (anticoagulation), infection, haemolysis, thromboembolism, limb ischaemia (femoral).
Fluid conservative (FACTT). FACTT (2006, NEJM): a conservative fluid strategy (CVP <4 or PAOP <8 — diurese) vs liberal (CVP 10-14 or PAOP 14-18) — the conservative arm had more ventilator-free days and fewer oxygenation days, but no mortality difference. Current practice is a fluid-conservative strategy (don't fluid overload; once resuscitated, achieve a neutral/negative balance and diurese if overloaded), which improves oxygenation and ventilator days. Balance this against adequate perfusion (not dry): assess volume (clinical, ultrasound, lactate) and, if adequate, restrict fluids.

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References25Show

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