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Acute Respiratory Distress Syndrome

Chapter 312 | Part 8: Critical Care Medicine

KEY CLINICAL POINTS

  • ARDS is a clinical syndrome of severe hypoxemia, diffuse pulmonary infiltrates, and respiratory failure with three phases: exudative, proliferative, and fibrotic.
  • The 2012 Berlin criteria define ARDS severity based on Pao2/Fio2 ratios (mild: 200-300 mmHg, moderate: 100-200 mmHg, severe: ≤ 100 mmHg).
  • Mechanical ventilation with low tidal volumes ( ≤ 6 mL/kg PBW) and plateau pressures ≤ 30 cmH2O is the cornerstone of management.
  • Prone positioning reduces 28-day mortality in severe ARDS (Pao2/Fio2 <150 mmHg) by 16.8%.
  • Nonpulmonary causes (sepsis, multiorgan failure) account for >80% of ARDS mortality.

1. DEFINITION & OVERVIEW

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of severe dyspnea, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure. ARDS is classified as direct lung injury (e.g., aspiration, toxic inhalation) or indirect lung injury (e.g., sepsis, trauma). The 2012 Berlin criteria define severity based on Pao2/Fio2 ratios, chest radiograph findings, and absence of hydrostatic edema. The 2023 update includes consideration of ARDS in nonintubated patients using Pao2/Fio2 ≤ 300 mmHg or Spo2/Fio2 ≤ 315 mmHg with high-flow nasal oxygen ≥ 30 L/min.

Table 312-1: Clinical Disorders Commonly Associated with ARDS

DIRECT LUNG INJURY INDIRECT LUNG INJURY
Pneumonia Sepsis
Aspiration of gastric contents Severe trauma
Pulmonary contusion Multiple bone fractures
Near-drowning Flail chest
Toxic inhalation injury Head trauma
Burns Multiple transfusions
Drug overdose Pancreatitis
Postcardiopulmonary bypass

Table 312-2: Diagnostic Criteria for ARDS Based on 2012 Berlin Criteria

SEVERITY: OXYGENATIONa ONSET CHEST RADIOGRAPHb ABSENCE OF LEFT ATRIAL HYPERTENSION
Mild: 200 mmHg < Pao2/Fio2 £300 mmHg Acute: Within 1 week of a clinical insult or new/worsening respiratory symptoms Bilateral opacities consistent with pulmonary edema not fully explained by effusions, lobar/lung collapse, or nodules Hydrostatic edema is not the primary cause of respiratory failure. If no ARDS risk factor is present, some objective evaluation (e.g., echocardiography) is required to rule out hydrostatic edema
Moderate: 100 mmHg < Pao2/Fio2 £200 mmHg
Severe: Pao2/Fio2 £100 mmHg

1.1 Diagnostic Criteria

ARDS is diagnosed based on the 2012 Berlin criteria: (1) acute onset within 1 week of a clinical insult, (2) bilateral opacities consistent with pulmonary edema not fully explained by hydrostatic edema, (3) Pao2/Fio2 ratios: mild (200-300 mmHg), moderate (100-200 mmHg), severe ( ≤ 100 mmHg). The 2023 update allows for noninvasive ventilation with PEEP ≥ 5 cmH2O and includes Spo2/Fio2 ratios for intubated patients.

1.2 Pathophysiology

ARDS involves exudative phase (alveolar edema, neutrophil infiltration), proliferative phase (interstitial inflammation, fibrosis), and fibrotic phase (pulmonary hypertension, bullae formation). Proinflammatory cytokines, lipid mediators, and microthrombi contribute to endothelial/epithelial injury and alveolar-capillary barrier disruption.

2. EPIDEMIOLOGY

Annual incidence prior to COVID-19 pandemic was ~60 cases/100,000 population. ~10% of ICU admissions involve ARDS. Mortality risk increases with age (>75 years: ~60% mortality vs <45 years: ~20%), chronic organ dysfunction (liver disease, alcohol abuse, immunosuppression), and severity of illness (Berlin criteria).

2.1 Risk Factors

Older age, chronic alcohol abuse, pancreatitis, pneumonia/sepsis (40-60%), trauma, multiple transfusions, drug overdose, and postcardiopulmonary bypass. Patients with multiple predisposing conditions have increased risk.

3. ETIOLOGY & PATHOPHYSIOLOGY

ARDS is caused by direct lung injury (toxic inhalation, aspiration) or indirect injury (sepsis, trauma). Pathophysiology involves proinflammatory cytokines (IL-1, IL-6, TNF- α ), lipid mediators, microthrombi, and endothelial/epithelial injury leading to alveolar-capillary barrier disruption and pulmonary edema.

3.1 Mechanisms

Neutrophil infiltration, protease release, oxidative stress, and mitochondrial dysfunction contribute to alveolar damage. Pulmonary vascular injury leads to microthrombi and fibrocellular proliferation, increasing pulmonary hypertension and dead space.

4. CLINICAL FEATURES

Exudative phase: rapid shallow breathing, hypoxemia, tachypnea. Proliferative phase: persistent hypoxemia, dyspnea, tachypnea. Fibrotic phase: pulmonary hypertension, bullae formation, and increased risk of pneumothorax. Chest x-ray shows bilateral opacities indistinguishable from cardiogenic edema but without cardiomegaly/pleural effusions.

4.1 Complications

Pulmonary hypertension, pneumothorax, hypercapnia, and multiorgan failure. Nonpulmonary causes (sepsis, organ failure) account for >80% of mortality.

5. DIFFERENTIAL DIAGNOSIS

Cardiogenic pulmonary edema, bilateral pneumonia, alveolar hemorrhage, acute interstitial lung disease, hypersensitivity pneumonitis, radiation pneumonitis, neurogenic pulmonary edema, and acute immunologic injury.

6. INVESTIGATIONS & DIAGNOSIS

Chest radiograph (bilateral opacities), arterial blood gas analysis (Pao2/Fio2 ratios), echocardiography to exclude hydrostatic edema, and CT scan for heterogeneity of lung involvement. 2023 updates allow ultrasound as an alternative imaging modality in resource-limited settings.

7. MANAGEMENT & TREATMENT

Low tidal volume ventilation ( ≤ 6 mL/kg PBW), plateau pressure ≤ 30 cmH2O, prone positioning in severe ARDS, fluid restriction to minimize left atrial pressure, and neuromuscular blockade for ventilator dyssynchrony. ECMO may be beneficial in select severe cases.

Table 312-3: Evidence-Based Recommendations for ARDS Therapies

TREATMENT RECOMMENDATIONa
Mechanical ventilation Low tidal volume (A), High-PEEP/open lung strategy (Bb), Prone positioning (Bb), Recruitment maneuvers (Cb), High-frequency ventilation (D)
Glucocorticoids Low-dose hydrocortisone in sepsis/refractory hypotension (Dc)
Inhaled vasodilators NO, inhaled epoprostenol (A)
ECMO Rescue therapy in severe ARDS (Bb)
Neuromuscular blockade Early use in severe ARDS with dyssynchrony (Cb)

7.1 Mechanical Ventilation

Low tidal volume (6 mL/kg PBW), high PEEP ( ≥ 5 cmH2O), prone positioning for severe ARDS, and recruitment maneuvers. Avoid high PEEP/Fio2 combinations without evidence of benefit.

7.2 Fluid Management

Restrict fluids to minimize left atrial filling pressures. Diuretics used cautiously to avoid hypoperfusion. Maintain MAP ≥ 65 mmHg.

7.3 Neuromuscular Blockade

Early neuromuscular blockade (cisatracurium) may improve survival in severe ARDS with ventilator dyssynchrony. Routine use not recommended due to lack of consistent benefit.

7.4 ECMO

Extracorporeal membrane oxygenation (ECMO) may be used as rescue therapy in severe ARDS with refractory hypoxemia, particularly in patients with sepsis or multiorgan failure.

8. PROGNOSIS & COMPLICATIONS

Mortality: 34.9% for mild ARDS, 40.3% for moderate, 46.1% for severe. Nonpulmonary causes (sepsis, multiorgan failure) account for >80% of deaths. Functional recovery varies, with many survivors remaining ventilator-dependent for prolonged periods.

8.1 Risk Factors

Age >75 years (~60% mortality), chronic organ dysfunction (liver disease, immunosuppression), and severity of ARDS (Berlin criteria).

9. SPECIAL CONSIDERATIONS

Pregnancy: ARDS in pregnancy has higher mortality due to maternal/fetal risks. Pediatrics: ARDS in children has better outcomes but requires careful ventilator management. Elderly: Increased mortality risk due to comorbidities and reduced physiological reserve.

10. KEY POINTS & CLINICAL PEARLS

  1. ARDS is a heterogeneous syndrome with three phases of injury. 2. Use low tidal volume ventilation with PEEP to minimize volutrauma. 3. Prone positioning reduces mortality in severe ARDS. 4. Nonpulmonary causes account for >80% of ARDS mortality. 5. Early neuromuscular blockade may benefit ventilator dyssynchrony. 6. ECMO is a rescue therapy for refractory hypoxemia. 7. Fluid management must balance left atrial pressure and organ perfusion.