ARDS & Respiratory Failure
Anaesthesia · Critical Care · lean revision notes
ARDS & Respiratory Failure
A perennially high-yield Critical Care topic for NEET PG, sitting at the intersection of physiology, anaesthesia, and medicine. Master the Berlin definition cut-offs, the Type I vs Type II distinction, and lung-protective ventilation — these three clusters generate the bulk of questions.
1. Respiratory failure: definition & classification
Respiratory failure is the inability of the respiratory system to maintain adequate gas exchange — i.e. failure to oxygenate the blood and/or eliminate carbon dioxide. It is a functional diagnosis based on arterial blood gas (ABG), not a single disease.
The classic ABG cut-offs (breathing room air, at sea level):
| Parameter | Threshold for respiratory failure |
|---|---|
| PaO₂ | < 60 mmHg (hypoxaemia) |
| PaCO₂ | > 50 mmHg (hypercapnia) |
| SaO₂ | < 90% (corresponds to PaO₂ ~60) |
High-yield: PaO₂ < 60 mmHg AND/OR PaCO₂ > 50 mmHg defines respiratory failure. The 60/50 rule is the single most-tested numeric fact here.
Type I vs Type II respiratory failure
This distinction is asked almost every year. Anchor it on the PaCO₂.
| Feature | Type I (Hypoxaemic) | Type II (Hypercapnic / Ventilatory) |
|---|---|---|
| PaO₂ | ↓ (< 60 mmHg) | ↓ |
| PaCO₂ | Normal or ↓ (low/normal) | ↑ (> 50 mmHg) |
| Core defect | Failure of oxygenation (gas exchange / V-Q mismatch, shunt) | Failure of ventilation (pump failure) |
| A–a gradient | Widened | Normal (in pure pump failure, e.g. drug overdose); widened if lung disease |
| Classic causes | ARDS, pneumonia, pulmonary oedema, PE, pulmonary fibrosis | COPD, neuromuscular disease (GBS, myasthenia), opioid/sedative overdose, chest wall disease, OHS |
| Mnemonic | "Type 1 = 1 gas abnormal (O₂)" | "Type 2 = 2 gases abnormal (O₂ + CO₂)" |
High-yield: Type I = oxygenation failure with wide A–a gradient; Type II = ventilation/pump failure with normal A–a gradient when the lungs themselves are healthy (e.g. opioid overdose, GBS). ARDS is the prototype of Type I.
Two additional types sometimes appear in textbooks:
- Type III (perioperative): atelectasis-related, a subset of Type I.
- Type IV (shock): hypoperfusion of respiratory muscles.
The five mechanisms of hypoxaemia
- V/Q mismatch — commonest cause overall (e.g. COPD, asthma); corrects with O₂.
- Shunt — blood bypasses ventilated alveoli (ARDS, consolidation, AVM); does NOT correct fully with 100% O₂ — the hallmark.
- Hypoventilation — ↑ PaCO₂, normal A–a gradient; corrects with O₂.
- Diffusion limitation — ILD, emphysema.
- Low inspired PO₂ — high altitude.
High-yield: Refractory hypoxaemia not corrected by 100% O₂ = right-to-left shunt, the physiological signature of ARDS.
A–a gradient
A–a O₂ gradient = PAO₂ − PaO₂, where PAO₂ = FiO₂ (PB − PH₂O) − PaCO₂/R. On room air ≈ 150 − PaCO₂/0.8 − PaO₂.
- Normal ≈ 5–15 mmHg (rises with age: ~ age/4 + 4).
- Normal A–a gradient + hypoxaemia → hypoventilation or low FiO₂.
- Widened A–a gradient + hypoxaemia → V/Q mismatch, shunt, or diffusion defect.
2. ARDS — Acute Respiratory Distress Syndrome
ARDS is an acute, diffuse, inflammatory lung injury causing increased pulmonary vascular permeability, non-cardiogenic pulmonary oedema, and severe hypoxaemia. It is the most severe form of acute lung injury and a leading cause of Type I respiratory failure in the ICU.
Berlin definition (2012) — the centerpiece
ARDS is diagnosed when ALL four criteria are met:
- Timing — within 1 week of a known clinical insult or new/worsening respiratory symptoms.
- Imaging — bilateral opacities on chest X-ray/CT, not fully explained by effusions, lobar/lung collapse, or nodules.
- Origin of oedema — respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g. echocardiography) to exclude hydrostatic oedema if no risk factor present. (The old PCWP < 18 mmHg criterion was removed.)
- Oxygenation — hypoxaemia graded by PaO₂/FiO₂ (P/F) ratio with PEEP/CPAP ≥ 5 cm H₂O.
| Severity | PaO₂/FiO₂ ratio (on PEEP ≥ 5) | Approx. mortality |
|---|---|---|
| Mild | 200 < P/F ≤ 300 | ~27% |
| Moderate | 100 < P/F ≤ 200 | ~32% |
| Severe | P/F ≤ 100 | ~45% |
High-yield: Berlin P/F cut-offs are 300 / 200 / 100 (mild / moderate / severe). The term "Acute Lung Injury (ALI)" and the old P/F ≤ 300 = ALI, ≤ 200 = ARDS framework are obsolete — Berlin abolished "ALI."
High-yield: Onset within 1 week, bilateral infiltrates, and oedema not cardiac in origin — these three plus the P/F ratio are the whole definition. PCWP is no longer required.
Mnemonic for ARDS criteria — "ARDS": Acute (≤ 1 week) · Ratio P/F low (≤ 300) · Diffuse bilateral infiltrates · Swan-Ganz/cardiac cause excluded.
Etiology
Divide into direct (pulmonary) and indirect (extrapulmonary) insults:
| Direct lung injury | Indirect lung injury |
|---|---|
| Pneumonia (commonest direct cause) | Sepsis (commonest overall cause) |
| Aspiration of gastric contents | Severe non-thoracic trauma / multiple transfusions (TRALI) |
| Pulmonary contusion | Acute pancreatitis |
| Near-drowning, inhalational injury | Major burns, fat embolism, DIC |
| COVID-19 pneumonia | Drug overdose, cardiopulmonary bypass |
High-yield: Sepsis is the single commonest cause of ARDS overall; pneumonia is the commonest direct/pulmonary cause.
Pathophysiology — Diffuse Alveolar Damage (DAD)
The histological hallmark of ARDS is diffuse alveolar damage. It evolves through three overlapping phases:
Insult → cytokine release (TNF-α, IL-1, IL-8) → neutrophil sequestration → alveolar-capillary membrane injury → protein-rich exudate → hyaline membranes → fibrosis
- Exudative phase (days 1–7): Damage to type I pneumocytes and capillary endothelium → increased permeability → protein-rich oedema fluid floods alveoli. Hyaline membranes (the histologic signature) form. Loss of surfactant (type II pneumocyte damage) → alveolar collapse, ↓ compliance.
- Proliferative phase (days 7–21): Type II pneumocyte proliferation (these are the regenerative cells), early fibroblast activity, attempted repair.
- Fibrotic phase (> 3 weeks): Collagen deposition, fibrosis → persistent ↓ compliance, pulmonary hypertension, dead-space increase.
Physiological consequences: intrapulmonary shunt (refractory hypoxaemia), ↓ lung compliance ("baby lung" — only a small portion of lung is aerated and available for ventilation), ↑ dead space, and pulmonary hypertension.
High-yield: Histologic hallmark = diffuse alveolar damage with hyaline membranes. Type I pneumocytes are damaged; type II pneumocytes proliferate to repair and also produce surfactant.
3. Clinical features
- Acute onset dyspnoea, tachypnoea, hypoxaemia developing 12–72 h after the insult.
- Refractory hypoxaemia, cyanosis, use of accessory muscles, bilateral crackles.
- No clinical signs of left heart failure (no raised JVP, gallop, or peripheral oedema attributable to cardiac cause).
- ABG: low PaO₂, low PaCO₂ early (tachypnoea → respiratory alkalosis); CO₂ rises late as the patient tires (fatigue) → ominous sign.
4. Diagnosis & investigations
- ABG — confirms hypoxaemia, computes P/F ratio. Investigation that grades severity.
- Chest X-ray / CT — bilateral diffuse alveolar opacities ("white-out" / bilateral ground-glass). CT classically shows heterogeneous, dependent (gravity-dependent) consolidation — the basis of the "baby lung" concept.
- Echocardiography — key to exclude cardiogenic pulmonary oedema (assess LV function); has replaced PCWP. A normal/low BNP and normal LV function support ARDS.
- Investigation of choice to grade severity: PaO₂/FiO₂ ratio on PEEP ≥ 5 cm H₂O.
- Identify the precipitant: cultures, lipase, etc.
High-yield: ARDS vs cardiogenic pulmonary oedema — echocardiography (or low BNP) distinguishes them now; the old Swan-Ganz/PCWP < 18 mmHg cut-off is historical.
5. Management
There is no specific drug that reverses ARDS — management is supportive, centred on treating the cause and lung-protective mechanical ventilation. The single intervention proven to reduce mortality is the low-tidal-volume strategy (ARMA / ARDSNet trial).
Lung-protective ventilation (ARDSNet protocol)
| Parameter | Target |
|---|---|
| Tidal volume (Vt) | 6 mL/kg of predicted (ideal) body weight (start 6; can reduce to 4) |
| Plateau pressure (Pplat) | ≤ 30 cm H₂O |
| Driving pressure (Pplat − PEEP) | Keep < 15 cm H₂O (strong mortality correlate) |
| PEEP | High enough to prevent collapse (titrate; higher PEEP for moderate–severe) |
| FiO₂ | Lowest to keep SpO₂ 88–95% / PaO₂ 55–80 mmHg |
| pH | Tolerate permissive hypercapnia (pH ≥ 7.20–7.25) |
High-yield: Low tidal volume 6 mL/kg PBW + plateau pressure ≤ 30 cm H₂O = the only ventilator strategy with a proven mortality benefit (ARDSNet/ARMA trial). This is THE most-tested management fact.
Permissive hypercapnia: deliberately accepting a high PaCO₂ (and mild acidosis) to avoid the barotrauma/volutrauma of large tidal volumes. Avoid in raised ICP.
Prone positioning
- For moderate–severe ARDS (P/F < 150), prone positioning for ≥ 16 hours/day improves oxygenation and reduces mortality (PROSEVA trial).
- Mechanism: more uniform distribution of ventilation, recruitment of dorsal (dependent) alveoli, better V/Q matching, reduced compression by the heart.
High-yield: Prone ventilation ≥ 16 h/day reduces mortality in severe ARDS (PROSEVA) — a favourite recent question.
Stepwise escalation of refractory hypoxaemia
Lung-protective ventilation → optimise PEEP → neuromuscular blockade (early, severe) → prone positioning ≥ 16 h → inhaled pulmonary vasodilator (nitric oxide/prostacyclin, rescue only) → veno-venous ECMO (refractory, EOLIA)
Other measures
- Conservative fluid strategy (FACTT trial) — less fluid → fewer ventilator days (no mortality change). Keep the lungs "dry."
- Neuromuscular blockade (cisatracurium) — early, short course in severe ARDS (ACURASYS) may improve outcomes; benefit debated by ROSE trial.
- Corticosteroids — useful in COVID-19 ARDS (dexamethasone, RECOVERY) and may help in moderate–severe early ARDS (DEXA-ARDS); not routine in all-comers.
- VV-ECMO — rescue for severe refractory hypoxaemia (P/F < 80, refractory) per EOLIA/CESAR.
- Inhaled nitric oxide / prostacyclin — transient oxygenation improvement only; no mortality benefit; rescue/bridge.
- NOT recommended/ineffective: routine high-dose steroids in late fibrotic phase, surfactant (adults), β-agonists, statins, liberal fluids.
High-yield: Inhaled NO improves oxygenation transiently but does NOT reduce mortality. Likewise high-frequency oscillatory ventilation (OSCILLATE/OSCAR) showed no benefit/harm.
Drug-of-choice quick list
- COVID-19 ARDS requiring O₂/ventilation → dexamethasone (6 mg/day).
- Pulmonary vasodilator rescue → inhaled nitric oxide.
- Paralysis for ventilator dyssynchrony → cisatracurium.
6. Complications
- Barotrauma / volutrauma: pneumothorax, pneumomediastinum, subcutaneous emphysema (from high pressures/volumes) — ventilator-induced lung injury (VILI).
- Ventilator-associated pneumonia (VAP).
- Pulmonary fibrosis (fibrotic phase) → chronic restrictive defect, reduced DLCO.
- Pulmonary hypertension and cor pulmonale.
- Multi-organ dysfunction syndrome (MODS) — most ARDS deaths are due to the underlying sepsis/MODS, not hypoxaemia itself.
- ICU-acquired weakness, oxygen toxicity, DVT/stress ulcers.
High-yield: Most ARDS patients die of multi-organ failure / sepsis, not from refractory hypoxaemia.
7. Key differentials
| Condition | Distinguishing feature |
|---|---|
| Cardiogenic pulmonary oedema | Raised JVP, S3 gallop, ↑ BNP, cardiomegaly, dilated upper-lobe vessels + Kerley B lines; echo shows poor LV function; responds to diuretics |
| Diffuse alveolar haemorrhage | Haemoptysis, falling haemoglobin, blood on BAL |
| Acute interstitial pneumonia (Hamman-Rich) | Idiopathic ARDS-like picture, DAD on biopsy, no identifiable trigger |
| Bilateral pneumonia | Fever, focal-then-diffuse, organism identified |
| TRALI | Within 6 h of transfusion |
The cardiogenic vs non-cardiogenic distinction is the highest-yield differential — see fluid origin criterion of Berlin.
8. Recently asked / exam angle
- Berlin P/F cut-offs (300/200/100) matched to mild/moderate/severe — direct recall and matching questions.
- Tidal volume in ARDS = 6 mL/kg PBW, plateau pressure ≤ 30 — repeatedly tested as "ventilator setting with mortality benefit."
- Prone positioning duration (≥ 16 h/day) and the trial name PROSEVA.
- Type I vs Type II respiratory failure — given a clinical vignette (GBS, opioid overdose, COPD, ARDS) identify the type and the A–a gradient.
- Histologic hallmark of ARDS = diffuse alveolar damage / hyaline membranes; type II pneumocytes proliferate.
- Refractory hypoxaemia / shunt not corrected by 100% O₂.
- Commonest cause of ARDS = sepsis; commonest direct cause = pneumonia/aspiration.
- Dexamethasone in COVID-19 ARDS (RECOVERY) — newer favourite.
- PCWP no longer part of the definition — common "which of the following is NOT a Berlin criterion" stem.
- Inhaled NO has no mortality benefit — classic distractor.
9. Rapid revision
- Respiratory failure = PaO₂ < 60 and/or PaCO₂ > 50 mmHg.
- Type I = hypoxaemic, ↓/normal CO₂, wide A–a gradient (ARDS, pneumonia, PE).
- Type II = hypercapnic pump failure, ↑ CO₂, normal A–a gradient if lungs healthy (overdose, GBS, COPD).
- ARDS Berlin P/F: ≤ 300 mild, ≤ 200 moderate, ≤ 100 severe (on PEEP ≥ 5).
- Berlin needs: ≤ 1 week onset, bilateral opacities, oedema not cardiac, low P/F. PCWP dropped.
- Sepsis = commonest cause; pneumonia/aspiration = commonest direct cause.
- Pathology = diffuse alveolar damage + hyaline membranes; type II pneumocytes regenerate & make surfactant.
- Hypoxaemia is from intrapulmonary shunt → not corrected by 100% O₂.
- Ventilation: Vt 6 mL/kg PBW, Pplat ≤ 30, driving pressure < 15, permissive hypercapnia — only strategy with mortality benefit (ARDSNet).
- Prone ≥ 16 h/day in severe ARDS (P/F < 150) lowers mortality (PROSEVA).
- Conservative fluids (FACTT) → fewer vent days; VV-ECMO for refractory hypoxaemia (EOLIA).
- Inhaled NO = oxygenation only, no survival benefit; dexamethasone helps COVID-19 ARDS; most deaths from MODS, not hypoxia.