ARDS and lung-protective ventilation · ICU Topics

[1]

CT chest showing bilateral diffuse ground-glass opacities consistent with ARDS, with a ventilator displaying low tidal volume settings — FigureARDS: bilateral pulmonary infiltrates from diffuse alveolar damage. The lung is not stiff everywhere — it is a 'baby lung' with reduced functional size, making standard tidal volumes cause volutrauma in the remaining healthy tissue. Lung-protective ventilation (Vt 6 mL/kg PBW) is the single most important intervention.

[1]

Definition and diagnosis

Berlin definition (2012)

The Berlin definition requires ALL of the following within 1 week of a known clinical insult:[3][2]

Timing: within 7 days of a precipitating insult (pneumonia, sepsis, aspiration, trauma, pancreatitis)
Chest imaging: bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules (on CXR or CT)
Origin of oedema: respiratory failure not fully explained by cardiac failure or fluid overload (echo to exclude hydrostatic oedema if no clear risk factor)
Oxygenation (with PEEP ≥5 cmH2O or CPAP ≥5): [1]

Berlin severity by PaO2/FiO2 ratio (click each)

PaO2/FiO2 <100

Mortality ~46%

Severe ARDS. P/F ratio <100. Mandatory proning (>=16 hours/day). Consider VV-ECMO referral if refractory despite optimised ventilation and proning.

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New global definition (2024)

The 2024 update (Kigali modification expanded):[4]

PaO2/FiO2 measured with any FiO2 (not just PEEP ≥5) — includes patients on high-flow nasal cannula
SpO2/FiO2 ratio <315 as a non-invasive alternative (for resource-limited settings)
Bilateral opacities on lung ultrasound accepted (not just CXR/CT)
Onset within 7 days retained

[1]

Causes

Direct lung injury

Pulmonary ARDS

Pneumonia (most common — viral, bacterial, fungal)
Aspiration of gastric contents
Pulmonary contusion
Fat embolism
Inhalation injury (smoke, chemical)
Near-drowning
Reperfusion pulmonary oedema

Indirect lung injury

Extrapulmonary ARDS

Sepsis (most common indirect cause)
Severe major trauma (multiple fractures)
Acute pancreatitis
Massive transfusion / TRALI
Cardiopulmonary bypass
Drug overdose
Burns (>30% TBSA)

[1]

Pathophysiology

The pathogenesis of ARDS involves three overlapping phases:[1][2]

1. Exudative phase (days 0-7):

Alveolar-capillary membrane disruption (endothelial and epithelial injury)
Increased permeability → protein-rich oedema fluid floods alveoli (non-cardiogenic pulmonary oedema)
Surfactant dysfunction (inactivation and reduced production) → atelectasis
Hyaline membranes form (proteinaceous debris + dead cells)
Neutrophil influx → release of proteases, reactive oxygen species, cytokines
Result: refractory hypoxaemia (V/Q mismatch, shunt) + reduced compliance (stiff lungs) [1]

2. Proliferative phase (days 7-21):

Type II pneumocyte proliferation → attempts to repair the epithelium
Fibroblast proliferation → early fibrosis
Resolution of pulmonary oedema if the insult is controlled
Some patients recover; others progress to fibrosis [1]

3. Fibrotic phase (weeks-months):

Pulmonary fibrosis → irreversible loss of lung compliance
Pulmonary hypertension (vascular remodelling)
Poor prognosis; prolonged ventilation [1]

Lung-protective ventilation

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The ARDSNet protocol (2000)

The landmark ARDSNet trial (NEJM 2000) randomised 861 patients with ALI/ARDS to low Vt (6 mL/kg PBW) vs traditional Vt (12 mL/kg PBW). The trial was stopped early for benefit.[5]

ARDSNet trial results

31%

Low Vt mortality

vs 40% traditional (p=0.007)

Absolute risk reduction

NNT = 11

6 mL/kg

Target Vt

Predicted body weight

30 cm

Plateau pressure limit

Reduce Vt if exceeded

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Ventilator settings

Lung-protective ventilation setup

Calculate predicted body weight (PBW)

Male: 50 + 0.91 x (height cm - 152.4). Female: 45.5 + 0.91 x (height cm - 152.4). Use PBW, NOT actual body weight — Vt is based on lung size, which correlates with height.

Set initial Vt = 8 mL/kg PBW

Then reduce by 1 mL/kg every 2-4 hours until Vt = 6 mL/kg PBW. Do not reduce below 4 mL/kg unless per specialist protocol.

Set respiratory rate = 18-35 bpm

Adjust to target pH 7.30-7.45. Permissive hypercapnia is acceptable (respiratory acidosis is tolerated to protect the lung). PaCO2 may rise to 60-80 mmHg if pH >7.20.

Titrate PEEP/FiO2

Use the ARDSNet PEEP/FiO2 ladder (lower or higher PEEP strategy). Higher PEEP strategy preferred for moderate-severe ARDS. Target SpO2 88-95% or PaO2 55-80 mmHg.

Monitor plateau pressure

Measure with 0.5-second inspiratory hold. Target Pplat <30 cmH2O. If >30, reduce Vt by 1 mL/kg steps (minimum 4 mL/kg).

Monitor driving pressure

Driving pressure = Pplat - PEEP. Target <15 cmH2O. Driving pressure >15 is independently associated with increased mortality.

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PEEP titration strategies

Strategy	Method	Pros	Cons
ARDSNet lower PEEP/FiO2	Table-based PEEP 5-24 based on FiO2	Simple, validated in ARDSNet trial	May under-treat severe ARDS
ARDSNet higher PEEP/FiO2	Higher PEEP for same FiO2	Better for moderate-severe ARDS	Risk of barotrauma/hypotension
Best PEEP / best compliance	Incremental PEEP trial; choose PEEP with best static compliance	Individualised	Time-consuming; needs paralysis
Driving pressure-guided	Titrate PEEP to minimise driving pressure (Pplat - PEEP)	Strongest association with survival	Requires plateau pressure measurement
Oesophageal pressure-guided (EPVent)	Use oesophageal balloon to estimate transpulmonary pressure	Accounts for chest wall compliance	PREVENT trial (2019): no mortality benefit; invasive[12]

The ARDSNet PEEP/FiO2 ladders

The two original ARDSNet protocol tables. Titrate downward as oxygenation improves; never reduce PEEP below 5. [1]

FiO2	0.30	0.40	0.40	0.50	0.50	0.60	0.70	0.70	0.70	0.80	0.90	0.90	0.90	1.0
Lower PEEP (cmH2O)	5	5	8	8	10	10	10	12	14	14	14	16	18	18-24
Higher PEEP (cmH2O)	5	5	10	10	12	14	14	14	16	16	18	20	20	22-24

Choosing between strategies: The 2010 Briel meta-analysis (individual patient data from 3 ALVEOLI/Express/LOVS trials) showed higher PEEP reduces mortality in moderate-severe ARDS (P/F <200) but offers no benefit — and possible harm — in mild ARDS (P/F >200).[20] The LOVS trial (Meade 2008) used the high-PEEP ladder with recruitment manoeuvres and showed no overall mortality benefit but reduced barotrauma.[19]

Driving pressure (ΔP)

Driving pressure = plateau pressure − PEEP. It is the dynamic strain delivered to the aerated lung with each breath — the variable most tightly coupled to the 'baby lung' that is actually being ventilated. [1]

The Amato et al. (NEJM 2015) analysis pooled 3,562 patients from 9 RCTs.[17] In multivariable analysis adjusting for P/F, PEEP and Vt:

Driving pressure >15 cmH2O was the ventilation variable most strongly associated with mortality — a stronger predictor than Vt, plateau pressure, or PEEP alone.
Reducing Vt only mattered if it also reduced ΔP; raising PEEP only helped if it reduced ΔP.
Implication: Target ΔP <15 cmH2O. If ΔP is >15, reduce Vt first (1 mL/kg steps to 4 mL/kg); if still high, PEEP may be on the flat/derecruiting portion of the curve — a trial of higher PEEP that reduces ΔP suggests recruitable lung. [1]

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Permissive hypercapnia

Lung-protective ventilation may result in hypoventilation (low Vt + high dead space). This causes respiratory acidosis (elevated PaCO2). This is accepted (permissive hypercapnia) because protecting the lung is more important than normalising PaCO2.[2]

Acceptable: PaCO2 up to 60-80 mmHg IF pH ≥7.20
If pH <7.20: increase RR (up to 35-40); consider bicarbonate infusion (controversial); do NOT increase Vt above 6 mL/kg
Contraindications to permissive hypercapnia: raised ICP (intracranial hypertension), severe pulmonary hypertension [1]

Adjunctive therapies

Prone positioning

Mechanism: Improves V/Q matching by:

Recruiting dorsal (previously collapsed) lung regions
Reducing shunt
More uniform ventilation distribution
Facilitates drainage of secretions
Reduces ventilator-induced lung injury (more homogeneous transpulmonary pressure)[6]

The PROSEVA trial (NEJM 2013): randomised 466 patients with severe ARDS (PaO2/FiO2 <150, FiO2 ≥60%, PEEP ≥5) to prone positioning for ≥16 hours vs supine.[6]

PROSEVA trial results

16%

Prone 28-day mortality

vs 33% supine (p<0.001)

50%

Relative risk reduction

NNT = 6

16 hrs

Minimum duration

per session, continuous

16%

Unadjusted hazard ratio

for death at 90 days

Indications: PaO2/FiO2 <150 despite optimised ventilation (after at least 4 hours of optimisation).[13]

Contraindications: spinal instability, unstable pelvic fractures, severe burns, pregnancy (relative), recent abdominal surgery (relative), raised ICP. [1]

Complications: facial pressure sores (most common), nerve compression, corneal abrasions, tube/line dislodvement (ETT, CVC, arterial line), haemodynamic instability during turning, cardiac arrest (rare). [1]

Neuromuscular blockade

ACURASYS trial (NEJM 2010): 340 patients with early severe ARDS, cisatracurium for 48 hours. Reduced 90-day mortality (31% vs 41%, p=0.05) and adjusted hazard ratio 0.68.[9]

ROSE trial (NEJM 2019): 1006 patients with moderate-severe ARDS (P/F <150), cisatracurium for 48 hours. NO mortality benefit (42.5% vs 42.8%, p=0.95). Higher rates of myocarditis/rhabdomyolysis with NMB.[10]

Current recommendation: Do NOT routinely use NMB in ARDS. Consider short (24-48 hour) infusion of cisatracurium for severe oxygenation failure (P/F <150) where ventilator dyssynchrony is problematic or profound hypoxaemia persists despite proning.[13]

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VV-ECMO for refractory ARDS

Indications: Severe ARDS (PaO2/FiO2 <80) despite optimised lung-protective ventilation, proning, and PEEP titration for >6-12 hours. Consider referral to an ECMO centre early.[7][11]

Key trials:

CESAR (Lancet 2009): referral to ECMO centre improved 6-month survival without severe disability (63% vs 47%, p=0.03). BUT: only 75% of the ECMO group actually received ECMO.[8]
EOLIA (NEJM 2018): early VV-ECMO vs conventional ventilation. No significant 60-day mortality benefit (35% vs 46%, p=0.09). BUT: 28% crossover from control to ECMO; Bayesian re-analysis suggests 85-96% probability of benefit.[7]
Meta-analysis (2020): individual patient data from EOLIA + 3 other trials suggests mortality benefit with VV-ECMO in severe ARDS.[11]

Corticosteroids (DEXA-ARDS)

The role of corticosteroids in ARDS has been debated for two decades. Current evidence supports early, moderate-dose dexamethasone in moderate-severe ARDS but NOT routine use in mild ARDS or late-phase unresolving ARDS. [1]

The DEXA-ARDS trial (Villar et al, Lancet Respir Med 2020): 277 patients with moderate-severe ARDS (P/F 200-280 within 24 hours of onset) given dexamethasone 20 mg/day x 5 days then 10 mg/day x 5 days vs placebo.[15]

DEXA-ARDS results

21%

Dexa 28-day mortality

vs 36% placebo (p=0.0048)

15 days

Ventilator-free days

vs 7.5 days placebo (p<0.0001)

20 mg

Daily dose x5 days

then 10 mg x5 days

NNT for mortality

at day 28

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Increased ventilator-free days (15 vs 7.5) and oxygenation-free days.
No signal of increased infection, gastroduodenal bleeding, or hyperglycaemia requiring intervention.
Caveat: enrolled only early (<24h), moderate-severe ARDS; benefit may not extend to late fibroproliferative disease. [1]

How steroids fit in practice: Consider dexamethasone 20 mg/day x 5 days (then taper) in moderate-severe ARDS within 72 hours of onset. Avoid in mild ARDS, in active untreated infection without septic shock, and in late (>14 day) unresolving ARDS (LAEDS/SSC 2012 trials showed harm when started late). Methylprednisolone 1 mg/kg/day for persistent ARDS is an older, weaker alternative. [1]

Higher PEEP and recruitment manoeuvres

Higher vs lower PEEP: The Briel individual-patient-data meta-analysis (2010, ALVEOLI/EXPRESS/LOVS) confirmed that higher PEEP improves survival only in moderate-severe ARDS (P/F <200) and is neutral/harmful in mild ARDS.[20] The LOVS trial (Meade 2008, n=983) combined the high-PEEP ladder with recruitment manoeuvres — no mortality benefit, but reassuringly less barotrauma with lung-protective Vt.[19]

Recruitment manoeuvres (RMs): NOT recommended routinely. The ART trial (Cavalcanti 2017, n=1,010) tested a stepwise incremental PEEP recruitment strategy + titrated PEEP vs a low-PEEP control in moderate-severe ARDS.[18]

Result: 28-day mortality 29.3% (recruitment) vs 24.6% (control), adjusted RR 1.20 (95% CI 1.01-1.42) — increased mortality with recruitment.
More barotrauma (pneumothorax requiring drainage), hypotension, and need for vasoactive drugs.
Conclusion: Aggressive staircase recruitment with high PEEP is harmful. Brief (40-second, 40 cmH2O) sustained-inflation RMs may be used selectively before proning or to assess recruitability, but not as routine therapy. [1]

ARDS subphenotypes (precision medicine)

ARDS is pathophysiologically and biologically heterogeneous. Latent class analysis of plasma biomarkers (Calfee et al, 2014) identified two reproducible subphenotypes that are biologically distinct and have markedly different outcomes.[16]

Hyperinflammatory (Type 1)

~65% of ARDS

Higher IL-6, IL-8, sTNFR-1, surfactant protein D
Lower PaO2/FiO2, more organ failures
Higher vasopressor requirement and longer ventilation
Mortality ~44% — clearly worse prognosis
More likely to benefit from higher PEEP, simvastatin, and anaemia-correcting strategies

Hypoinflammatory (Type 2)

~35% of ARDS

Lower inflammatory biomarker profile
Less severe oxygenation impairment
Fewer non-pulmonary organ failures
Mortality ~23%
May be harmed by aggressive therapies that benefit Type 1 (e.g. higher PEEP, simvastatin)

Driving pressure >15 cmH2O was the ventilation variable most strongly associated with death — stronger than Vt, PEEP, or plateau pressure alone

Practice change

Driving pressure <15 cmH2O added to lung-protective targets

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Management algorithm summary

Complete ARDS management pathway

Recognise and diagnose

Berlin criteria within 7 days of insult. Bilateral opacities, P/F <300 with PEEP >=5, exclude cardiac failure (echo).

Start lung-protective ventilation

Vt 6 mL/kg PBW. RR 18-35 for pH 7.30-7.45. Pplat <30. Driving pressure <15. Permissive hypercapnia accepted if pH >=7.20.

Titrate PEEP and FiO2

Use higher PEEP/FiO2 table for moderate-severe. Target SpO2 88-95%. Consider best-compliance or driving-pressure-guided PEEP.

Prone positioning (if P/F <150)

Continuous prone for >=16 hours per session. Minimum 3-4 sessions. Reduce if P/F improves to >150 for 4 hours in supine.

Early dexamethasone (DEXA-ARDS)

For moderate-severe ARDS within 24-72 h of onset: dexamethasone 20 mg/day x5 days, then 10 mg/day x5 days. Reduced 28-day mortality (21% vs 36%) and increased ventilator-free days. Avoid in late (>14 day) unresolving ARDS.

Consider adjuncts

Short NMB only for severe dyssynchrony. Inhaled pulmonary vasodilators (NO/prostacyclin) as bridge. Recruitment manoeuvres — controversial, not routine.

VV-ECMO referral (if P/F <80 despite above)

Refer early to ECMO centre. Indications: P/F <80 for >6h, or P/F <50 for >3h, or pH <7.25 with RR maxed. Must be at a centre with capability.

Treat the cause

Antibiotics for pneumonia. Source control for sepsis. Stop causative drugs. Treat pancreatitis. This is the most important step for recovery.

Conservative fluid strategy

FACTT trial: conservative fluid strategy (target even-to-negative fluid balance after resuscitation) improves oxygenation and ventilator-free days without increasing renal failure.

Driving pressure check

Measure ΔP = Pplat - PEEP on every check. Target <15 cmH2O. If ΔP >15, reduce Vt (1 mL/kg to 4 mL/kg) or trial higher PEEP that *reduces* ΔP (indicates recruitable lung). Amato 2015: ΔP is the strongest ventilation predictor of survival.

Weaning

Daily sedation breaks + SBT when P/F >200, FiO2 <40%, PEEP <8, stable for 30 min. Follow weaning protocol.

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Prognosis

ARDS outcomes

34%

Mild ARDS mortality

P/F 200-300

40%

Moderate mortality

P/F 100-200

46%

Severe mortality

P/F <100

~25%

Overall mortality

Has improved with lung-protective ventilation

Prognostic factors: age, comorbidities, severity (P/F ratio), driving pressure, cause (direct vs indirect — direct may have better prognosis)[1]
Long-term sequelae: cognitive impairment (~30%), PTSD (~25%), depression (~40%), physical weakness, pulmonary fibrosis in survivors[2]

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Clinical pearls

High-yield points for the CICM/FFICM exam

ARDS = bilateral infiltrates + P/F <300 with PEEP >=5 + not cardiac. Berlin: mild 200-300, moderate 100-200, severe <100.
ARDSNet (2000): Vt 6 mL/kg PBW reduced mortality from 40% to 31%. Single most important intervention. Use PBW (height-based), NOT actual weight.[5]
Plateau pressure <30 cmH2O and driving pressure <15 cmH2O — both independently associated with survival.[13]
PROSEVA (2013): prone >=16 hours reduced 28-day mortality from 33% to 16% for P/F <150. NNT = 6.[6]
ROSE (2019): routine cisatracurium does NOT improve survival — do not routinely paralyse ARDS patients.[10]
EOLIA (2018): VV-ECMO did not show significant mortality benefit (p=0.09) but 28% crossover; use selectively for refractory cases.[7]
Permissive hypercapnia is ACCEPTED — PaCO2 up to 60-80 if pH >=7.20. Do NOT increase Vt to normalise CO2.
Driving pressure = Pplat - PEEP. If >15, reduce Vt first (not PEEP). Amato et al. showed driving pressure is the ventilation variable most strongly associated with survival.
Conservative fluid strategy (FACTT trial) improves outcomes — aim for even-to-negative balance after initial resuscitation.
The 'baby lung' concept: the lung is not uniformly diseased. 6 mL/kg of a normal-sized lung is too much for the small remaining functional lung in ARDS.
Contraindications to prone positioning: spinal instability, unstable pelvic fractures, raised ICP, severe burns.
Long-term outcomes: ~30% cognitive impairment, ~25% PTSD, ~40% depression in survivors.
DEXA-ARDS (Villar 2020): dexamethasone 20 mg/day x5 then 10 mg/day x5, started within 24 h of moderate-severe ARDS, reduced 28-day mortality 21% vs 36% (NNT ~6) and doubled ventilator-free days. Add to your Vt + proning bundle.[15]
ARDS subphenotypes (Calfee 2014): hyperinflammatory (Type 1, ~65%, mortality ~44%) vs hypoinflammatory (Type 2, ~35%, mortality ~23%). Hyperinflammatory benefits from higher PEEP and may benefit simvastatin; hypoinflammatory may be harmed. The 2020 parsimonious classifier uses IL-8, sTNFR-1, bicarbonate, platelets.[16][22]
Amato (NEJM 2015): driving pressure >15 cmH2O is the ventilation variable most strongly associated with death — stronger than Vt, PEEP, or plateau pressure. Measure ΔP on every ventilator check.[17]
ART trial (2017): aggressive staircase recruitment + titrated high PEEP increased 28-day mortality (29.3% vs 24.6%) with more barotrauma — do NOT use routine recruitment manoeuvres.[18]
Briel meta-analysis (2010): higher PEEP reduces mortality only in moderate-severe ARDS (P/F <200) — neutral or harmful in mild ARDS. Use the higher PEEP/FiO2 ladder selectively.[20]
FACTT (Wiedemann 2006): conservative fluid strategy (target CVP <4 or PAOP <8) increased ventilator-free days (14.6 vs 11.2) and ICU-free days without increasing renal failure or dialysis.[21]
The 4 pillars of ARDS management: (1) low Vt, (2) adequate PEEP, (3) prone for P/F <150, (4) early dexamethasone (DEXA-ARDS). Add ECMO only for refractory P/F <80.
Two IV access, two arterial lines, foley, and a pre-oxygenation plan before proning. Pressure points (forehead, chin, shoulders, iliac crests, knees, toes) must be padded — facial pressure ulcers are the most common proning complication.

Red flags

Critical points in ARDS management

Driving pressure >15 cmH2O is associated with increased mortality — reduce Vt immediately; do not sacrifice lung protection for oxygenation.[13]
ROSE trial (2019): routine cisatracurium does NOT improve survival in moderate-severe ARDS — do not routinely paralyse.[10]
EOLIA trial: VV-ECMO did not significantly reduce mortality (p=0.09) — refer selectively for refractory cases only (P/F <80 despite optimised ventilation + proning).[7]
Do NOT use recruitment manoeuvres routinely — associated with increased mortality in some studies (ART trial 2017 — halted for harm).
Permissive hypercapnia is contraindicated in raised ICP — the cerebral vasodilation from high CO2 increases cerebral blood flow and ICP.
SpO2 target 88-95% — do not chase higher SpO2 at the cost of lung-injurious ventilator settings (high Vt, high pressure, high FiO2 causing oxygen toxicity).
Prone positioning requires adequate staffing (minimum 4-5 people) and preparation — ETT dislodgement during turning can be catastrophic.
ART trial (2017): aggressive staircase recruitment + titrated high PEEP increased mortality (29.3% vs 24.6%, RR 1.20) with more barotrauma and hypotension — do NOT use routine recruitment manoeuvres.[18]
Higher PEEP can harm mild ARDS (P/F >200) — Briel meta-analysis (2010) showed benefit only in moderate-severe; use the higher PEEP/FiO2 ladder selectively.[20]
DEXA-ARDS started LATE (>14 days, unresolving ARDS) may cause harm — steroids benefit only early (<72 h) moderate-severe ARDS. Avoid in active untreated infection without septic shock.[15]
Subphenotype matters for therapy response — hyperinflammatory ARDS may benefit from higher PEEP/simvastatin; hypoinflammatory ARDS may be harmed by the same. Phenotyping is not yet routine bedside practice but is high-yield for exams.[16][22]
FACTT conservative fluid strategy is NOT dehydration — it targets euvolaemia/even balance after resuscitation; do not withhold fluids from a patient in shock. Renal failure and dialysis rates were NOT increased in FACTT.[21]
Driving pressure >15 cmH2O is the ventilation variable MOST strongly associated with death (Amato 2015) — even when Vt and plateau pressure are 'acceptable'. Always check ΔP, not just Pplat.[17]

References

[1]Matthay MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management Lancet, 2022.PMID 36070788
[2]Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment JAMA, 2018.PMID 29466596
[3]ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition JAMA, 2012.PMID 22797452
[4]Matthay MA, Hughes G, Liu KD, et al. A New Global Definition of Acute Respiratory Distress Syndrome Am J Respir Crit Care Med, 2024.PMID 37487152
[5]The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome N Engl J Med, 2000.PMID 10793162
[6]Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome N Engl J Med, 2013.PMID 23688302
[7]Combes A, Hajage D, Capellier G, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome N Engl J Med, 2018.PMID 29791822
[8]Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial Lancet, 2009.PMID 19762075
[9]Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome N Engl J Med, 2010.PMID 20843245
[10]Moss M, Huang DT, Brower RG, et al. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome N Engl J Med, 2019.PMID 31112383
[11]Munshi L, Walkey A, Goligher E, et al. ECMO for severe ARDS: systematic review and individual patient data meta-analysis Intensive Care Med, 2020.PMID 33021684
[12]Writing Group for the PREVENT Trial Investigators. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA, 2019.PMID 30776290
[13]Fan E, Del Sorbo L, Goligher EC, et al. Treatment of ARDS With Prone Positioning Chest, 2017.PMID 27400909
[14]Cochran A, Batac D, Ramanujan V, et al. Diagnosis and Epidemiology of Acute Respiratory Failure Crit Care Clin, 2024.PMID 38432693
[15]Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial Lancet Respir Med, 2020.PMID 32043986
[16]Calfee CS, Delucchi KL, Sinha P, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials Lancet Respir Med, 2014.PMID 24853585
[17]Amato MBP, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome N Engl J Med, 2015.PMID 25693014
[18]Cavalcanti AB, Suzumura ÉA, Laranjeira LN, et al. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA, 2017.PMID 28973363
[19]Meade MO, Cook DJ, Guyatt GH, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial JAMA, 2008.PMID 18270352
[20]Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis JAMA, 2010.PMID 20197533
[21]Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury N Engl J Med, 2006.PMID 16714767
[22]Calfee CS, Delucchi K, Parsons PE, et al. Development and validation of parsimonious algorithms to classify acute respiratory distress syndrome phenotypes: a secondary analysis of randomised controlled trials Lancet Respir Med, 2020.PMID 31948926

[1]

Definition and diagnosis

Berlin definition (2012)

The Berlin definition requires ALL of the following within 1 week of a known clinical insult:[3][2]

Timing: within 7 days of a precipitating insult (pneumonia, sepsis, aspiration, trauma, pancreatitis)
Chest imaging: bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules (on CXR or CT)
Origin of oedema: respiratory failure not fully explained by cardiac failure or fluid overload (echo to exclude hydrostatic oedema if no clear risk factor)
Oxygenation (with PEEP ≥5 cmH2O or CPAP ≥5): [1]

Berlin severity by PaO2/FiO2 ratio (click each)

PaO2/FiO2 <100

Mortality ~46%

Severe ARDS. P/F ratio <100. Mandatory proning (>=16 hours/day). Consider VV-ECMO referral if refractory despite optimised ventilation and proning.

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New global definition (2024)

The 2024 update (Kigali modification expanded):[4]

PaO2/FiO2 measured with any FiO2 (not just PEEP ≥5) — includes patients on high-flow nasal cannula
SpO2/FiO2 ratio <315 as a non-invasive alternative (for resource-limited settings)
Bilateral opacities on lung ultrasound accepted (not just CXR/CT)
Onset within 7 days retained

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Causes

Direct lung injury

Pulmonary ARDS

Pneumonia (most common — viral, bacterial, fungal)
Aspiration of gastric contents
Pulmonary contusion
Fat embolism
Inhalation injury (smoke, chemical)
Near-drowning
Reperfusion pulmonary oedema

Indirect lung injury

Extrapulmonary ARDS

Sepsis (most common indirect cause)
Severe major trauma (multiple fractures)
Acute pancreatitis
Massive transfusion / TRALI
Cardiopulmonary bypass
Drug overdose
Burns (>30% TBSA)

[1]

Pathophysiology

The pathogenesis of ARDS involves three overlapping phases:[1][2]

1. Exudative phase (days 0-7):

Alveolar-capillary membrane disruption (endothelial and epithelial injury)
Increased permeability → protein-rich oedema fluid floods alveoli (non-cardiogenic pulmonary oedema)
Surfactant dysfunction (inactivation and reduced production) → atelectasis
Hyaline membranes form (proteinaceous debris + dead cells)
Neutrophil influx → release of proteases, reactive oxygen species, cytokines
Result: refractory hypoxaemia (V/Q mismatch, shunt) + reduced compliance (stiff lungs) [1]

2. Proliferative phase (days 7-21):

Type II pneumocyte proliferation → attempts to repair the epithelium
Fibroblast proliferation → early fibrosis
Resolution of pulmonary oedema if the insult is controlled
Some patients recover; others progress to fibrosis [1]

3. Fibrotic phase (weeks-months):

Pulmonary fibrosis → irreversible loss of lung compliance
Pulmonary hypertension (vascular remodelling)
Poor prognosis; prolonged ventilation [1]

Lung-protective ventilation

[1]

The ARDSNet protocol (2000)

The landmark ARDSNet trial (NEJM 2000) randomised 861 patients with ALI/ARDS to low Vt (6 mL/kg PBW) vs traditional Vt (12 mL/kg PBW). The trial was stopped early for benefit.[5]

ARDSNet trial results

31%

Low Vt mortality

vs 40% traditional (p=0.007)

Absolute risk reduction

NNT = 11

6 mL/kg

Target Vt

Predicted body weight

30 cm

Plateau pressure limit

Reduce Vt if exceeded

[1]

Ventilator settings

Lung-protective ventilation setup

Calculate predicted body weight (PBW)

Male: 50 + 0.91 x (height cm - 152.4). Female: 45.5 + 0.91 x (height cm - 152.4). Use PBW, NOT actual body weight — Vt is based on lung size, which correlates with height.

Set initial Vt = 8 mL/kg PBW

Then reduce by 1 mL/kg every 2-4 hours until Vt = 6 mL/kg PBW. Do not reduce below 4 mL/kg unless per specialist protocol.

Set respiratory rate = 18-35 bpm

Adjust to target pH 7.30-7.45. Permissive hypercapnia is acceptable (respiratory acidosis is tolerated to protect the lung). PaCO2 may rise to 60-80 mmHg if pH >7.20.

Titrate PEEP/FiO2

Use the ARDSNet PEEP/FiO2 ladder (lower or higher PEEP strategy). Higher PEEP strategy preferred for moderate-severe ARDS. Target SpO2 88-95% or PaO2 55-80 mmHg.

Monitor plateau pressure

Measure with 0.5-second inspiratory hold. Target Pplat <30 cmH2O. If >30, reduce Vt by 1 mL/kg steps (minimum 4 mL/kg).

Monitor driving pressure

Driving pressure = Pplat - PEEP. Target <15 cmH2O. Driving pressure >15 is independently associated with increased mortality.

[1]

PEEP titration strategies

Strategy	Method	Pros	Cons
ARDSNet lower PEEP/FiO2	Table-based PEEP 5-24 based on FiO2	Simple, validated in ARDSNet trial	May under-treat severe ARDS
ARDSNet higher PEEP/FiO2	Higher PEEP for same FiO2	Better for moderate-severe ARDS	Risk of barotrauma/hypotension
Best PEEP / best compliance	Incremental PEEP trial; choose PEEP with best static compliance	Individualised	Time-consuming; needs paralysis
Driving pressure-guided	Titrate PEEP to minimise driving pressure (Pplat - PEEP)	Strongest association with survival	Requires plateau pressure measurement
Oesophageal pressure-guided (EPVent)	Use oesophageal balloon to estimate transpulmonary pressure	Accounts for chest wall compliance	PREVENT trial (2019): no mortality benefit; invasive[12]

The ARDSNet PEEP/FiO2 ladders

The two original ARDSNet protocol tables. Titrate downward as oxygenation improves; never reduce PEEP below 5. [1]

FiO2	0.30	0.40	0.40	0.50	0.50	0.60	0.70	0.70	0.70	0.80	0.90	0.90	0.90	1.0
Lower PEEP (cmH2O)	5	5	8	8	10	10	10	12	14	14	14	16	18	18-24
Higher PEEP (cmH2O)	5	5	10	10	12	14	14	14	16	16	18	20	20	22-24

Driving pressure (ΔP)

The Amato et al. (NEJM 2015) analysis pooled 3,562 patients from 9 RCTs.[17] In multivariable analysis adjusting for P/F, PEEP and Vt:

Driving pressure >15 cmH2O was the ventilation variable most strongly associated with mortality — a stronger predictor than Vt, plateau pressure, or PEEP alone.
Reducing Vt only mattered if it also reduced ΔP; raising PEEP only helped if it reduced ΔP.
Implication: Target ΔP <15 cmH2O. If ΔP is >15, reduce Vt first (1 mL/kg steps to 4 mL/kg); if still high, PEEP may be on the flat/derecruiting portion of the curve — a trial of higher PEEP that reduces ΔP suggests recruitable lung. [1]

[1]

Permissive hypercapnia

Acceptable: PaCO2 up to 60-80 mmHg IF pH ≥7.20
If pH <7.20: increase RR (up to 35-40); consider bicarbonate infusion (controversial); do NOT increase Vt above 6 mL/kg
Contraindications to permissive hypercapnia: raised ICP (intracranial hypertension), severe pulmonary hypertension [1]

Adjunctive therapies

Prone positioning

Mechanism: Improves V/Q matching by:

Recruiting dorsal (previously collapsed) lung regions
Reducing shunt
More uniform ventilation distribution
Facilitates drainage of secretions
Reduces ventilator-induced lung injury (more homogeneous transpulmonary pressure)[6]

The PROSEVA trial (NEJM 2013): randomised 466 patients with severe ARDS (PaO2/FiO2 <150, FiO2 ≥60%, PEEP ≥5) to prone positioning for ≥16 hours vs supine.[6]

PROSEVA trial results

16%

Prone 28-day mortality

vs 33% supine (p<0.001)

50%

Relative risk reduction

NNT = 6

16 hrs

Minimum duration

per session, continuous

16%

Unadjusted hazard ratio

for death at 90 days

Indications: PaO2/FiO2 <150 despite optimised ventilation (after at least 4 hours of optimisation).[13]

Contraindications: spinal instability, unstable pelvic fractures, severe burns, pregnancy (relative), recent abdominal surgery (relative), raised ICP. [1]

Neuromuscular blockade

ACURASYS trial (NEJM 2010): 340 patients with early severe ARDS, cisatracurium for 48 hours. Reduced 90-day mortality (31% vs 41%, p=0.05) and adjusted hazard ratio 0.68.[9]

[1]

VV-ECMO for refractory ARDS

Indications: Severe ARDS (PaO2/FiO2 <80) despite optimised lung-protective ventilation, proning, and PEEP titration for >6-12 hours. Consider referral to an ECMO centre early.[7][11]

Key trials:

CESAR (Lancet 2009): referral to ECMO centre improved 6-month survival without severe disability (63% vs 47%, p=0.03). BUT: only 75% of the ECMO group actually received ECMO.[8]
EOLIA (NEJM 2018): early VV-ECMO vs conventional ventilation. No significant 60-day mortality benefit (35% vs 46%, p=0.09). BUT: 28% crossover from control to ECMO; Bayesian re-analysis suggests 85-96% probability of benefit.[7]
Meta-analysis (2020): individual patient data from EOLIA + 3 other trials suggests mortality benefit with VV-ECMO in severe ARDS.[11]

Corticosteroids (DEXA-ARDS)

DEXA-ARDS results

21%

Dexa 28-day mortality

vs 36% placebo (p=0.0048)

15 days

Ventilator-free days

vs 7.5 days placebo (p<0.0001)

20 mg

Daily dose x5 days

then 10 mg x5 days

NNT for mortality

at day 28

[1]

Increased ventilator-free days (15 vs 7.5) and oxygenation-free days.
No signal of increased infection, gastroduodenal bleeding, or hyperglycaemia requiring intervention.
Caveat: enrolled only early (<24h), moderate-severe ARDS; benefit may not extend to late fibroproliferative disease. [1]

Higher PEEP and recruitment manoeuvres

Result: 28-day mortality 29.3% (recruitment) vs 24.6% (control), adjusted RR 1.20 (95% CI 1.01-1.42) — increased mortality with recruitment.
More barotrauma (pneumothorax requiring drainage), hypotension, and need for vasoactive drugs.
Conclusion: Aggressive staircase recruitment with high PEEP is harmful. Brief (40-second, 40 cmH2O) sustained-inflation RMs may be used selectively before proning or to assess recruitability, but not as routine therapy. [1]

ARDS subphenotypes (precision medicine)

Hyperinflammatory (Type 1)

~65% of ARDS

Higher IL-6, IL-8, sTNFR-1, surfactant protein D
Lower PaO2/FiO2, more organ failures
Higher vasopressor requirement and longer ventilation
Mortality ~44% — clearly worse prognosis
More likely to benefit from higher PEEP, simvastatin, and anaemia-correcting strategies

Hypoinflammatory (Type 2)

~35% of ARDS

Lower inflammatory biomarker profile
Less severe oxygenation impairment
Fewer non-pulmonary organ failures
Mortality ~23%
May be harmed by aggressive therapies that benefit Type 1 (e.g. higher PEEP, simvastatin)

Practice change

Driving pressure <15 cmH2O added to lung-protective targets

[1]

Management algorithm summary

Complete ARDS management pathway

Recognise and diagnose

Berlin criteria within 7 days of insult. Bilateral opacities, P/F <300 with PEEP >=5, exclude cardiac failure (echo).

Start lung-protective ventilation

Vt 6 mL/kg PBW. RR 18-35 for pH 7.30-7.45. Pplat <30. Driving pressure <15. Permissive hypercapnia accepted if pH >=7.20.

Titrate PEEP and FiO2

Use higher PEEP/FiO2 table for moderate-severe. Target SpO2 88-95%. Consider best-compliance or driving-pressure-guided PEEP.

Prone positioning (if P/F <150)

Continuous prone for >=16 hours per session. Minimum 3-4 sessions. Reduce if P/F improves to >150 for 4 hours in supine.

Early dexamethasone (DEXA-ARDS)

Consider adjuncts

Short NMB only for severe dyssynchrony. Inhaled pulmonary vasodilators (NO/prostacyclin) as bridge. Recruitment manoeuvres — controversial, not routine.

VV-ECMO referral (if P/F <80 despite above)

Refer early to ECMO centre. Indications: P/F <80 for >6h, or P/F <50 for >3h, or pH <7.25 with RR maxed. Must be at a centre with capability.

Treat the cause

Antibiotics for pneumonia. Source control for sepsis. Stop causative drugs. Treat pancreatitis. This is the most important step for recovery.

Conservative fluid strategy

FACTT trial: conservative fluid strategy (target even-to-negative fluid balance after resuscitation) improves oxygenation and ventilator-free days without increasing renal failure.

Driving pressure check

Weaning

Daily sedation breaks + SBT when P/F >200, FiO2 <40%, PEEP <8, stable for 30 min. Follow weaning protocol.

[1]

Prognosis

ARDS outcomes

34%

Mild ARDS mortality

P/F 200-300

40%

Moderate mortality

P/F 100-200

46%

Severe mortality

P/F <100

~25%

Overall mortality

Has improved with lung-protective ventilation

Prognostic factors: age, comorbidities, severity (P/F ratio), driving pressure, cause (direct vs indirect — direct may have better prognosis)[1]
Long-term sequelae: cognitive impairment (~30%), PTSD (~25%), depression (~40%), physical weakness, pulmonary fibrosis in survivors[2]

Exam practice

SAQ — Severe ARDS management

10 minutes · 10 marks

[1]

SAQ — Moderate ARDS and prone positioning (PROSEVA)

10 minutes · 10 marks

[1]

SAQ — Severe refractory ARDS and VV-ECMO (EOLIA criteria)

10 minutes · 10 marks

[1]

Clinical pearls

High-yield points for the CICM/FFICM exam

ARDS = bilateral infiltrates + P/F <300 with PEEP >=5 + not cardiac. Berlin: mild 200-300, moderate 100-200, severe <100.
ARDSNet (2000): Vt 6 mL/kg PBW reduced mortality from 40% to 31%. Single most important intervention. Use PBW (height-based), NOT actual weight.[5]
Plateau pressure <30 cmH2O and driving pressure <15 cmH2O — both independently associated with survival.[13]
PROSEVA (2013): prone >=16 hours reduced 28-day mortality from 33% to 16% for P/F <150. NNT = 6.[6]
ROSE (2019): routine cisatracurium does NOT improve survival — do not routinely paralyse ARDS patients.[10]
EOLIA (2018): VV-ECMO did not show significant mortality benefit (p=0.09) but 28% crossover; use selectively for refractory cases.[7]
Permissive hypercapnia is ACCEPTED — PaCO2 up to 60-80 if pH >=7.20. Do NOT increase Vt to normalise CO2.
Driving pressure = Pplat - PEEP. If >15, reduce Vt first (not PEEP). Amato et al. showed driving pressure is the ventilation variable most strongly associated with survival.
Conservative fluid strategy (FACTT trial) improves outcomes — aim for even-to-negative balance after initial resuscitation.
The 'baby lung' concept: the lung is not uniformly diseased. 6 mL/kg of a normal-sized lung is too much for the small remaining functional lung in ARDS.
Contraindications to prone positioning: spinal instability, unstable pelvic fractures, raised ICP, severe burns.
Long-term outcomes: ~30% cognitive impairment, ~25% PTSD, ~40% depression in survivors.
DEXA-ARDS (Villar 2020): dexamethasone 20 mg/day x5 then 10 mg/day x5, started within 24 h of moderate-severe ARDS, reduced 28-day mortality 21% vs 36% (NNT ~6) and doubled ventilator-free days. Add to your Vt + proning bundle.[15]
ARDS subphenotypes (Calfee 2014): hyperinflammatory (Type 1, ~65%, mortality ~44%) vs hypoinflammatory (Type 2, ~35%, mortality ~23%). Hyperinflammatory benefits from higher PEEP and may benefit simvastatin; hypoinflammatory may be harmed. The 2020 parsimonious classifier uses IL-8, sTNFR-1, bicarbonate, platelets.[16][22]
Amato (NEJM 2015): driving pressure >15 cmH2O is the ventilation variable most strongly associated with death — stronger than Vt, PEEP, or plateau pressure. Measure ΔP on every ventilator check.[17]
ART trial (2017): aggressive staircase recruitment + titrated high PEEP increased 28-day mortality (29.3% vs 24.6%) with more barotrauma — do NOT use routine recruitment manoeuvres.[18]
Briel meta-analysis (2010): higher PEEP reduces mortality only in moderate-severe ARDS (P/F <200) — neutral or harmful in mild ARDS. Use the higher PEEP/FiO2 ladder selectively.[20]
FACTT (Wiedemann 2006): conservative fluid strategy (target CVP <4 or PAOP <8) increased ventilator-free days (14.6 vs 11.2) and ICU-free days without increasing renal failure or dialysis.[21]
The 4 pillars of ARDS management: (1) low Vt, (2) adequate PEEP, (3) prone for P/F <150, (4) early dexamethasone (DEXA-ARDS). Add ECMO only for refractory P/F <80.
Two IV access, two arterial lines, foley, and a pre-oxygenation plan before proning. Pressure points (forehead, chin, shoulders, iliac crests, knees, toes) must be padded — facial pressure ulcers are the most common proning complication.

Red flags

Critical points in ARDS management

Driving pressure >15 cmH2O is associated with increased mortality — reduce Vt immediately; do not sacrifice lung protection for oxygenation.[13]
ROSE trial (2019): routine cisatracurium does NOT improve survival in moderate-severe ARDS — do not routinely paralyse.[10]
EOLIA trial: VV-ECMO did not significantly reduce mortality (p=0.09) — refer selectively for refractory cases only (P/F <80 despite optimised ventilation + proning).[7]
Do NOT use recruitment manoeuvres routinely — associated with increased mortality in some studies (ART trial 2017 — halted for harm).
Permissive hypercapnia is contraindicated in raised ICP — the cerebral vasodilation from high CO2 increases cerebral blood flow and ICP.
SpO2 target 88-95% — do not chase higher SpO2 at the cost of lung-injurious ventilator settings (high Vt, high pressure, high FiO2 causing oxygen toxicity).
Prone positioning requires adequate staffing (minimum 4-5 people) and preparation — ETT dislodgement during turning can be catastrophic.
ART trial (2017): aggressive staircase recruitment + titrated high PEEP increased mortality (29.3% vs 24.6%, RR 1.20) with more barotrauma and hypotension — do NOT use routine recruitment manoeuvres.[18]
Higher PEEP can harm mild ARDS (P/F >200) — Briel meta-analysis (2010) showed benefit only in moderate-severe; use the higher PEEP/FiO2 ladder selectively.[20]
DEXA-ARDS started LATE (>14 days, unresolving ARDS) may cause harm — steroids benefit only early (<72 h) moderate-severe ARDS. Avoid in active untreated infection without septic shock.[15]
Subphenotype matters for therapy response — hyperinflammatory ARDS may benefit from higher PEEP/simvastatin; hypoinflammatory ARDS may be harmed by the same. Phenotyping is not yet routine bedside practice but is high-yield for exams.[16][22]
FACTT conservative fluid strategy is NOT dehydration — it targets euvolaemia/even balance after resuscitation; do not withhold fluids from a patient in shock. Renal failure and dialysis rates were NOT increased in FACTT.[21]
Driving pressure >15 cmH2O is the ventilation variable MOST strongly associated with death (Amato 2015) — even when Vt and plateau pressure are 'acceptable'. Always check ΔP, not just Pplat.[17]

References

[1]Matthay MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management Lancet, 2022.PMID 36070788
[2]Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment JAMA, 2018.PMID 29466596
[3]ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition JAMA, 2012.PMID 22797452
[4]Matthay MA, Hughes G, Liu KD, et al. A New Global Definition of Acute Respiratory Distress Syndrome Am J Respir Crit Care Med, 2024.PMID 37487152
[5]The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome N Engl J Med, 2000.PMID 10793162
[6]Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome N Engl J Med, 2013.PMID 23688302
[7]Combes A, Hajage D, Capellier G, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome N Engl J Med, 2018.PMID 29791822
[8]Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial Lancet, 2009.PMID 19762075
[9]Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome N Engl J Med, 2010.PMID 20843245
[10]Moss M, Huang DT, Brower RG, et al. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome N Engl J Med, 2019.PMID 31112383
[11]Munshi L, Walkey A, Goligher E, et al. ECMO for severe ARDS: systematic review and individual patient data meta-analysis Intensive Care Med, 2020.PMID 33021684
[12]Writing Group for the PREVENT Trial Investigators. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA, 2019.PMID 30776290
[13]Fan E, Del Sorbo L, Goligher EC, et al. Treatment of ARDS With Prone Positioning Chest, 2017.PMID 27400909
[14]Cochran A, Batac D, Ramanujan V, et al. Diagnosis and Epidemiology of Acute Respiratory Failure Crit Care Clin, 2024.PMID 38432693
[15]Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial Lancet Respir Med, 2020.PMID 32043986
[16]Calfee CS, Delucchi KL, Sinha P, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials Lancet Respir Med, 2014.PMID 24853585
[17]Amato MBP, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome N Engl J Med, 2015.PMID 25693014
[18]Cavalcanti AB, Suzumura ÉA, Laranjeira LN, et al. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA, 2017.PMID 28973363
[19]Meade MO, Cook DJ, Guyatt GH, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial JAMA, 2008.PMID 18270352
[20]Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis JAMA, 2010.PMID 20197533
[21]Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury N Engl J Med, 2006.PMID 16714767
[22]Calfee CS, Delucchi K, Parsons PE, et al. Development and validation of parsimonious algorithms to classify acute respiratory distress syndrome phenotypes: a secondary analysis of randomised controlled trials Lancet Respir Med, 2020.PMID 31948926

Your progress

Definition and diagnosis

Berlin definition (2012)

PaO2/FiO2 <100

New global definition (2024)

Causes

Direct lung injury

Indirect lung injury

Pathophysiology

Lung-protective ventilation

The ARDSNet protocol (2000)

Ventilator settings

Calculate predicted body weight (PBW)

Set initial Vt = 8 mL/kg PBW

Set respiratory rate = 18-35 bpm

Titrate PEEP/FiO2

Monitor plateau pressure

Monitor driving pressure

PEEP titration strategies

The ARDSNet PEEP/FiO2 ladders

Driving pressure (ΔP)

Permissive hypercapnia

Adjunctive therapies

Prone positioning

Neuromuscular blockade

VV-ECMO for refractory ARDS

Corticosteroids (DEXA-ARDS)

Higher PEEP and recruitment manoeuvres

ARDS subphenotypes (precision medicine)

Hyperinflammatory (Type 1)

Hypoinflammatory (Type 2)

Evidence and landmark trials

ARDSNet

PROSEVA

ROSE

EOLIA

PREVENT

DEXA-ARDS

ART

LOVS

Amato et al.

Management algorithm summary

Recognise and diagnose

Start lung-protective ventilation

Titrate PEEP and FiO2

Prone positioning (if P/F <150)

Early dexamethasone (DEXA-ARDS)

Consider adjuncts

VV-ECMO referral (if P/F <80 despite above)

Treat the cause

Conservative fluid strategy

Driving pressure check

Weaning

Prognosis

Exam practice

SAQ — Severe ARDS management

SAQ — Moderate ARDS and prone positioning (PROSEVA)

SAQ — Severe refractory ARDS and VV-ECMO (EOLIA criteria)

Clinical pearls

Red flags

References

Your progress

Definition and diagnosis

Berlin definition (2012)

PaO2/FiO2 <100

New global definition (2024)

Causes

Direct lung injury

Indirect lung injury

Pathophysiology

Lung-protective ventilation

The ARDSNet protocol (2000)

Ventilator settings

Calculate predicted body weight (PBW)

Set initial Vt = 8 mL/kg PBW

Set respiratory rate = 18-35 bpm

Titrate PEEP/FiO2

Monitor plateau pressure

Monitor driving pressure

PEEP titration strategies