Prepare detailed, point‑wise notes on acute respiratory distress syndrome (ARDS) using the latest guidelines and articles, with subheadings highlighting all important points for maximum exam marks.

Acute Respiratory Distress Syndrome (ARDS): Comprehensive Exam Notes

Definition and Diagnostic Criteria

ARDS is diagnosed when acute respiratory symptoms develop within 1 week of a known clinical insult, with bilateral pulmonary opacities on imaging, PaO₂/FiO₂ ≤300 mmHg (measured at minimum PEEP 5 cmH₂O), and respiratory failure not fully explained by cardiac failure or fluid overload. 1, 2

Core Diagnostic Components

• Timing: Onset within 1 week of known clinical insult or new/worsening respiratory symptoms 2, 3
• Imaging: Bilateral opacities on chest radiograph or CT not fully explained by effusions, lobar collapse, or nodules 2, 3
• Oxygenation: PaO₂/FiO₂ ≤300 mmHg with minimum PEEP of 5 cmH₂O 4, 1
• Origin of edema: Not fully explained by cardiac failure or fluid overload; requires objective assessment (echocardiography) when no clear ARDS risk factor is present 2, 3

Severity Classification (Berlin Definition)

• Mild ARDS: 200 < PaO₂/FiO₂ ≤300 mmHg 4, 1, 5
• Moderate ARDS: 100 < PaO₂/FiO₂ ≤200 mmHg 4, 1, 5
• Severe ARDS: PaO₂/FiO₂ ≤100 mmHg 4, 1, 5

Critical Diagnostic Pitfalls

• PEEP requirement: PaO₂/FiO₂ ratio must be calculated at minimum 5 cmH₂O PEEP; failure to do so results in inaccurate severity staging 2
• Cardiac exclusion: Active exclusion of cardiogenic pulmonary edema via echocardiography is mandatory when no clear ARDS risk factor exists 2, 3
• ARDS mimics: Diffuse interstitial lung diseases, widespread pulmonary infections, and drug-induced lung injury can present identically and require alternative treatments 4, 2

Pathophysiology

Inflammatory Cascade

• Alveolar-capillary barrier injury: Leukocyte infiltration, local immune activation, and injury to alveolar endothelial and epithelial cells 1, 2
• Increased vascular permeability: Results in protein-rich pulmonary edema and loss of aerated lung tissue 1, 2
• Inflammatory mediators: Neutrophil activation, cytokine release (IL-1, IL-6, IL-8, TNF-α), and oxidant stress 1

Histopathological Progression

• Exudative phase (days 1-7): Diffuse alveolar damage with hyaline membrane formation 2
• Fibroproliferative phase (days 7-21): Type II pneumocyte proliferation and early fibrosis 2
• Fibrotic phase (>3 weeks): Established pulmonary fibrosis in non-resolving cases 2

Physiological Consequences

• Surfactant depletion: Loss of alveolar stability and increased work of breathing 1, 2
• Intrapulmonary shunting: Extensive right-to-left shunting causing refractory hypoxemia 1
• Decreased lung compliance: Reduced functional residual capacity and "baby lung" phenomenon 1

Epidemiology and Prognosis

• Incidence: Affects approximately 10% of ICU admissions and 25% of mechanically ventilated patients 4, 5
• Mortality: In-hospital mortality remains 30-40% overall, with severe ARDS mortality 46-60% 1, 2, 6
• Global burden: Over 3 million cases annually worldwide, resulting in approximately 75,000 deaths annually in the United States alone 5

Mechanical Ventilation Strategies

Lung-Protective Ventilation (STRONG RECOMMENDATION)

All ARDS patients must receive low tidal volume ventilation with 4-8 ml/kg predicted body weight and plateau pressure ≤30 cmH₂O. 4, 1

• Tidal volume: 4-8 ml/kg predicted body weight (NOT actual body weight) 4, 1
• Plateau pressure limit: ≤30 cmH₂O to minimize ventilator-induced lung injury 4, 1
• Driving pressure: Monitor and minimize (plateau pressure minus PEEP); lower driving pressure associated with improved survival 1
• Permissive hypercapnia: Accept PaCO₂ elevation to maintain lung-protective parameters 4

PEEP Strategy

• Higher PEEP: Conditional recommendation for moderate-severe ARDS to improve oxygenation and recruitment 4, 1
• PEEP selection: Based on gas exchange, hemodynamic status, lung recruitability, end-expiratory transpulmonary pressure, and driving pressure 4, 1
• Esophageal pressure monitoring: Consider measuring esophageal pressure to calculate transpulmonary pressure and guide PEEP titration 4, 1

Recruitment Maneuvers

• Conditional recommendation: May be used in moderate-severe ARDS but avoid prolonged recruitment maneuvers 4, 1
• Low confidence: Evidence quality is limited; use judiciously 4

Oxygenation Targets

• Target PaO₂: 70-90 mmHg 4, 1
• Target SaO₂: 92-97% 4, 1
• Avoid hyperoxia: Excessive oxygen may worsen lung injury 4

Adjunctive Therapies

Prone Positioning (STRONG RECOMMENDATION)

Prone positioning for >12 hours daily is mandatory in severe ARDS (PaO₂/FiO₂ <150 mmHg). 4, 1, 5

• Duration: Minimum 12 hours per day, ideally 16-18 hours 4
• Indication: PaO₂/FiO₂ <150 mmHg despite optimal ventilation 4, 1
• Mortality benefit: Significant reduction in mortality demonstrated in severe ARDS 4, 5
• Mechanism: Improves ventilation-perfusion matching, reduces ventral lung compression, and promotes more homogeneous lung inflation 5

Neuromuscular Blocking Agents

• Cisatracurium: Consider continuous infusion for 48 hours in early severe ARDS 1
• Indication: PaO₂/FiO₂ <150 mmHg within first 48 hours of ARDS 1
• Caution: Balance benefit of improved ventilator synchrony against risk of ICU-acquired weakness 5

Corticosteroids

• Selective use: Consider in selected patients with ARDS, particularly when initiated early 1
• Evidence: Moderate-quality evidence supports use in specific subgroups 1
• Timing: Early initiation (within first week) may be more beneficial than late administration 1

High-Frequency Oscillatory Ventilation (STRONG RECOMMENDATION AGAINST)

• Do NOT use: Routine use of HFOV in moderate-severe ARDS is strongly contraindicated 4
• Evidence: High-quality evidence shows no benefit and possible harm 4

Rescue Therapies for Refractory Hypoxemia

Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO)

• Indication: Very severe ARDS failing conventional management including prone positioning and neuromuscular blockade 1
• Criteria: Consider when PaO₂/FiO₂ <80 mmHg despite maximal conventional therapy 1
• Specialized centers: Should only be performed at experienced ECMO centers 1

Inhaled Vasodilators

• Inhaled nitric oxide or prostacyclin: May improve oxygenation temporarily but no mortality benefit demonstrated 5
• Use: Reserve for severe refractory hypoxemia as bridge to other therapies 5

Fluid Management

Conservative Fluid Strategy

• Goal: Maintain adequate intravascular volume while avoiding fluid overload 1
• Timing: Implement conservative fluid management once shock is resolved 1
• Rationale: Excess fluid worsens pulmonary edema and prolongs mechanical ventilation 1

Sedation and Ventilator Weaning

Sedation Management

• Minimize sedation: Reduce sedation as gas exchange, respiratory mechanics, and hemodynamics improve 4
• Daily sedation interruption: Implement protocols for daily awakening trials 4

Spontaneous Breathing Trials

• Indication: Assess eligibility for ventilator weaning when underlying illness resolves and respiratory status improves 6
• Partial ventilator support: Promote respiratory muscle activity to prevent diaphragm atrophy 4

Supportive Care

Prophylaxis

• Stress ulcer prophylaxis: Proton pump inhibitors or H2-receptor antagonists for all mechanically ventilated ARDS patients 6
• Venous thromboembolism prophylaxis: Pharmacologic prophylaxis (low molecular weight heparin or unfractionated heparin) unless contraindicated 6

Nutritional Support

• Early enteral nutrition: Initiate within 24-48 hours when hemodynamically stable 6
• Route: Prefer enteral over parenteral nutrition 6

Common Etiologies and Risk Factors

Direct Lung Injury (Pulmonary ARDS)

• Pneumonia: Most common cause, bacterial or viral 6, 5
• Aspiration: Gastric contents, near-drowning 6
• Inhalation injury: Smoke, toxic gases 6
• Pulmonary contusion: Trauma 6

Indirect Lung Injury (Extrapulmonary ARDS)

• Sepsis: Second most common cause overall 6, 5
• Severe trauma: Polytrauma, burns 6
• Pancreatitis: Acute severe pancreatitis 6
• Transfusion-related: Transfusion-related acute lung injury (TRALI) 4
• Drug-induced: Various medications and toxins 4

Heterogeneity and Precision Medicine Considerations

Three Domains of Heterogeneity

• Aetiological heterogeneity: Different underlying causes (pneumonia, sepsis, trauma, aspiration) may respond differently to specific interventions 4
• Physiological heterogeneity: Variable lung recruitability, compliance, and dead space fraction 4
• Biological heterogeneity: Distinct inflammatory phenotypes (hyperinflammatory vs. hypoinflammatory) with different treatment responses 4

Clinical Implications

• Subphenotype identification: Emerging evidence suggests two biological subphenotypes with differential responses to PEEP, fluid management, and pharmacotherapy 4
• Failed therapeutic trials: Historical failure of anti-inflammatory, anticoagulant, and antioxidant therapies likely due to treating heterogeneous populations without phenotype-specific targeting 4, 2
• Future direction: Precision medicine approaches identifying treatable traits and endotypes may improve therapeutic success 4

Therapies WITHOUT Proven Benefit (Do NOT Use Routinely)

Pharmacologic Agents

• β2-agonists: No benefit and possible harm demonstrated 5
• Statins: No mortality benefit in ARDS treatment 5
• Keratinocyte growth factor: Not beneficial 5
• Aspirin: Not effective for ARDS prevention in high-risk patients 5
• N-acetylcysteine: No proven benefit 5
• Surfactant: No benefit in adult ARDS 5

Long-Term Sequelae and Follow-Up

Post-ARDS Syndrome

• Functional impairment: Diminished exercise capacity and physical function persist for months to years 6
• Mental health: High rates of depression, anxiety, and post-traumatic stress disorder 6
• Quality of life: Significantly reduced health-related quality of life 6
• Cognitive impairment: Memory and executive function deficits common 6

Follow-Up Recommendations

• Chest radiograph: Repeat at 6 weeks if respiratory symptoms persist or in high-risk patients (smokers, age >50) 4
• Advanced imaging: Consider CT thorax and bronchoscopy if chest radiograph remains abnormal at follow-up 4
• Primary care continuity: Ongoing care by primary care physician beneficial for addressing long-term complications 6

Key Exam Points Summary

• Berlin Definition supersedes AECC definition: Improved predictive validity for mortality with severity-based stratification 5, 3
• Mandatory interventions: Low tidal volume ventilation (4-8 ml/kg PBW) and prone positioning (>12 hrs/day) in severe ARDS are non-negotiable 4, 1
• PEEP requirement for diagnosis: Must measure PaO₂/FiO₂ at minimum 5 cmH₂O PEEP 1, 2
• Mortality remains high: 30-40% overall, 46-60% in severe ARDS despite optimal management 1, 2, 6
• No pharmacologic cure: Treatment remains supportive; multiple anti-inflammatory and pathophysiology-targeted drugs have failed 4, 5
• Heterogeneity is fundamental: ARDS encompasses diverse aetiological, physiological, and biological phenotypes requiring precision approaches 4