---

Acute Lung Injury (ALI) / ARDS — Comprehensive MD Exam Answer (15 Marks)

---

1. Definition & Historical Context

• ALI: PaO₂/FiO₂ ≤ 300 mmHg
• ARDS: PaO₂/FiO₂ ≤ 200 mmHg

---

2. Berlin Definition of ARDS (2012)

Severity Stratification:

---

3. Etiology / Causes

Direct (Pulmonary) Causes:

• Pneumonia (bacterial, viral, fungal) — most common
• Aspiration of gastric contents
• Pulmonary contusion
• Inhalation injury / toxic gas exposure
• Near-drowning
• Fat embolism

Indirect (Extrapulmonary) Causes:

• Sepsis — most common overall cause
• Severe trauma / polytrauma
• Burns
• Pancreatitis (acute severe)
• Massive transfusion / transfusion-related ALI (TRALI)
• Cardiopulmonary bypass
• Drug overdose (heroin, aspirin, barbiturates)
• DIC

Mnemonic for causes: "ARDS PAIN" Aspiration, Radiation, Drug/DIC, Sepsis, Pancreatitis, ALI-TRALI, Infection/Inhalation, Near-drowning

---

4. Pathophysiology

Phase 1 — Exudative Phase (Day 1–7)

• Injury to type I pneumocytes and pulmonary capillary endothelium
• Increased alveolo-capillary permeability → protein-rich exudate floods alveoli
• Neutrophil activation → release of proteases, reactive oxygen species (ROS), inflammatory cytokines (IL-1β, IL-6, TNF-α)
• Hyaline membrane formation (fibrin + plasma proteins)
• Diffuse alveolar damage (DAD) — pathological hallmark
• Surfactant dysfunction → alveolar collapse, atelectasis
• Results in: Hypoxaemia, reduced compliance, V/Q mismatch + intrapulmonary shunt

Phase 2 — Proliferative Phase (Day 7–21)

• Type II pneumocyte proliferation attempts repair
• Organisation of exudate; fibroblast invasion
• Most patients improve; some progress to fibrosis

Phase 3 — Fibrotic Phase (>21 days, minority)

• Progressive collagen deposition → pulmonary fibrosis
• Bullae formation → increased risk of pneumothorax
• Pulmonary hypertension

Key Pathophysiological Consequences:

---

5. Clinical Features

Symptoms:

• Severe dyspnoea of rapid onset (within hours to days of insult)
• Dry cough
• Restlessness, anxiety, confusion (hypoxaemia)

Signs:

• Tachypnoea (RR >30/min)
• Tachycardia
• Cyanosis (central)
• Use of accessory muscles
• Bilateral crepitations on auscultation
• Features of the underlying cause (fever in sepsis, abdominal tenderness in pancreatitis)
• Progression to respiratory failure requiring mechanical ventilation

---

6. Investigations

1. Arterial Blood Gas (ABG):

• Hypoxaemia: PaO₂/FiO₂ ratio ≤ 300 (refractory to supplemental O₂)
• Early: Respiratory alkalosis (hyperventilation)
• Late: Respiratory acidosis (fatigue, failure)

2. Chest X-Ray (CXR):

• Bilateral diffuse airspace opacities ("white-out")
• No cardiomegaly, no pleural effusions (distinguishes from cardiogenic oedema)
• Typically spares costophrenic angles early

3. CT Chest (Gold Standard Imaging):

• Dependent consolidation + non-dependent ground-glass opacities
• "Baby lung" concept — only ~30% aerated lung in severe ARDS
• Helps identify pneumothorax, fibrosis, underlying cause

4. Echocardiography:

• Excludes left heart failure (PCWP < 18 mmHg in ARDS)
• Assesses right ventricular strain (acute cor pulmonale)

5. Labs:

• CBC: Leucocytosis / leucopenia (sepsis)
• Procalcitonin, CRP (infection)
• Cultures (blood, sputum, BAL)
• LFT, RFT (multi-organ dysfunction)
• Coagulation profile (DIC)
• Serum amylase/lipase (pancreatitis)

---

7. ARDS CXR — Imaging Example

---

8. Differential Diagnosis

---

9. Management

A. Treat Underlying Cause:

• Antibiotics for sepsis/pneumonia
• Source control (drainage, surgery)
• Discontinue offending drug

B. Lung-Protective Mechanical Ventilation (Cornerstone)

Low Vt ventilation reduced mortality by 22% (ARDSNet trial)

C. Prone Positioning

• For severe ARDS (PaO₂/FiO₂ < 150) — ≥ 16 hours/day
• PROSEVA Trial (2013): 28-day mortality reduced from 32.8% → 16%
• Mechanism: Recruits dependent atelectatic lung, improves V/Q matching, reduces VILI

D. PEEP Optimisation

• Higher PEEP strategy in moderate-severe ARDS (ALVEOLI, LOVS, ExPress trials)
• Prevents alveolar de-recruitment at end-expiration
• Must balance: alveolar recruitment vs. overdistension

E. Neuromuscular Blockade (NMB)

• Cisatracurium infusion for 48 hours in moderate-severe ARDS
• ACURASYS Trial: Improved 90-day survival, reduced barotrauma
• Note: ROSE trial (2019) did not confirm benefit — still debated

F. Corticosteroids

• Methylprednisolone in select cases:
  • Early moderate-severe ARDS (within 14 days): May reduce duration of MV
  • COVID-19 ARDS: Dexamethasone 6 mg/day × 10 days (RECOVERY trial) — mortality benefit
  • Late ARDS (>14 days): Avoid — worsens outcomes

G. Conservative Fluid Management

• FACTT Trial (ARDSNet): Conservative fluid strategy → fewer ventilator days, no increase in renal failure
• Target: Euvolaemia / slight negative fluid balance
• Avoid fluid overload (worsens pulmonary oedema)

H. Rescue Therapies (Refractory ARDS):

I. General ICU Supportive Care:

• Nutritional support (enteral preferred, early)
• VTE prophylaxis
• Stress ulcer prophylaxis
• Glycaemic control
• Minimise sedation (SAT/SBT protocols)
• Head-of-bed elevation (30–45°) to prevent VAP

---

10. Complications

---

11. Prognosis

• Overall mortality: ~40% (ranges 27–45% by severity)
• Most deaths are from multi-organ failure, not hypoxaemia per se
• Survivors: ~50–70% regain near-normal lung function by 6–12 months
• Predictors of poor outcome: Age > 60, severe hypoxaemia, non-pulmonary organ failure, sepsis as cause, fibroproliferative phase

---

12. Summary Table for Quick Revision

---

• Harrison's Principles of Internal Medicine, 21st Edition, p. 8195
• Acute Respiratory Distress Syndrome: Definition, Phenotyping and Respiratory Support Strategies, p. 2 (ESICM/ERS Guidelines)
• ARDSNet ARMA Trial (2000), PROSEVA Trial (2013), FACTT Trial, RECOVERY Trial (2020)