Acute Respiratory Distress Syndrome¶

Chapter 312 | Part 8: Critical Care Medicine · Part 8 – Critical Care Medicine · Chapter 312

Key Clinical Points¶

ARDS is a clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure.
Severity is graded by the Berlin Criteria based on PaO2/FiO2 ratio: Mild (200–300), Moderate (100–200), and Severe (≤100).
Mechanical ventilation goals include low tidal volume (6 mL/kg predicted body weight) and plateau pressure ≤30 cmH2O.
Prone positioning is recommended for severe ARDS (PaO2/FiO2 <150 mmHg) to reduce 28-day mortality.
Early neuromuscular blockade may increase survival in severe ARDS but is not recommended for routine use in moderate-to-severe cases.
Glucocorticoids are not recommended for routine use; low-dose hydrocortisone may be considered in sepsis or severe pneumonia.
Mortality is largely attributable to nonpulmonary causes, such as sepsis and multi-organ failure.
Age is a significant risk factor: patients >75 years have a ~60% mortality rate compared to ~20% for those <45 years.
Fluid management aims to minimize pulmonary edema while maintaining adequate perfusion (MAP ≥ 65 mmHg).
ECMO may be used as a rescue therapy for select patients with severe ARDS who fail standard management.

DEFINITION & OVERVIEW¶

• Definition (Harrison's 22e): Acute respiratory distress syndrome (ARDS) is a clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure. • Clinical Context: ◦ ARDS results from diffuse lung injury from various medical and surgical disorders. ◦ Injury may be direct (e.g., toxic inhalation) or indirect (e.g., sepsis). ◦ A newer global definition is emerging for resource-poor settings that does not rely on arterial blood gases, chest radiography, or specific PEEP requirements. • Epidemiology: ◦ Annual incidence: ~60 cases per 100,000 population (pre-COVID). ◦ ICU Prevalence: Approximately 10% of all intensive care unit (ICU) admissions involve patients with ARDS.

ETIOLOGY¶

Clinical Causes¶

• Prevalence: Most cases (>80%) are caused by a small number of clinical disorders. ◦ Pneumonia and sepsis: 40–60% of cases. ◦ Other common causes: Aspiration of gastric contents, trauma, multiple transfusions, and drug overdose. ◦ Surgical conditions (in trauma): Pulmonary contusion, multiple bone fractures, and chest wall trauma/flail chest. ◦ Rare causes: Head trauma, near-drowning, toxic inhalation, and burns. • Risk Factors: ◦ Age, chronic alcohol abuse, pancreatitis, and severity of critical illness. ◦ Trauma patients with an APACHE II score ≥16 have a 2.5-fold increased risk of developing ARDS. • Table 312-1 (Clinical Disorders): ◦ Direct Lung Injury: Pneumonia, Aspiration of gastric contents, Pulmonary contusion, Near-drowning, Toxic inhalation injury. ◦ Indirect Lung Injury: Sepsis, Severe trauma, Multiple bone fractures, Flail chest, Head trauma, Burns, Multiple transfusions, Drug overdose, Pancreatitis, Postcardiopulmonary bypass.

CLINICAL COURSE AND PATHOPHYSIOLOGY¶

• Exudative Phase (Day 0–7): ◦ Mechanism: Injury to alveolar capillary endothelial cells and type I pneumocytes → loss of barrier integrity → accumulation of protein-rich edema fluid. ◦ Inflammatory Response: Increased cytokines (IL-1, IL-6, IL-8, TNF-α) and lipid mediators (leukotriene B) → recruitment of neutrophils. ◦ Result: Formation of hyaline membrane whorls; pulmonary vascular injury leading to microthrombi and increased pulmonary resistance. • Proliferative Phase (Day 7–21): ◦ Mechanism: Initiation of lung repair, organization of exudates, shift from neutrophil- to lymphocyte-predominant infiltrates. ◦ Cellular Response: Type II pneumocytes proliferate along alveolar basement membranes → synthesize new pulmonary surfactant → differentiate into type I pneumocytes. • Fibrotic Phase (After Day 21): ◦ Mechanism: Conversion of edema/exudate to extensive alveolar-duct and interstitial fibrosis. ◦ Consequences: Marked disruption of acinar architecture, emphysema-like changes, pulmonary hypertension, reduced lung compliance, and increased pulmonary dead space. • Clinical Note on PEEP: ◦ Recent trials show no benefit of routine use of esophageal pressure-guided PEEP titration over empiric high PEEP-FiO2 titration. ◦ Lung biopsy evidence for fibrosis can be used to generate a static pressure-volume curve; setting PEEP just above the lower inflection point maximizes respiratory system compliance. Measuring esophageal pressures helps estimate transpulmonary pressure, especially in patients with stiff chest walls.

DIFFERENTIAL DIAGNOSIS¶

• Common Overlapping Conditions: ◦ Cardiogenic pulmonary edema (distinguished by absence of primary heart failure). ◦ Bilateral pneumonia. ◦ Alveolar hemorrhage. • Less Common Considerations: ◦ Acute interstitial lung diseases (e.g., acute interstitial pneumonitis). ◦ Acute immunologic injury (e.g., hypersensitivity pneumonitis). ◦ Toxin injury (e.g., radiation pneumonitis). ◦ Neurogenic pulmonary edema.

INVESTIGATIONS & DIAGNOSIS¶

Imaging: ◦ Chest Radiograph: Look for bilateral opacities consistent with pulmonary edema. ◦ CT Scan: Identify extent of consolidation and dependent atelectasis.
Exclusion of Cardiac Etiology: ◦ If no ARDS risk factor is present → perform echocardiography to rule out hydrostatic edema (ensure heart failure is not the primary cause).
Berlin Criteria (Table 312-2): ◦ Timing: Within 1 week of clinical insult. ◦ Imaging: Bilateral opacities not fully explained by effusions, collapse, or nodules. ◦ Physiology: Hydrostatic edema is not the primary cause of respiratory failure. ◦ Oxygenation Severity: ◦ Mild: $200 < PaO_2/FiO_2 leq 300 mmHg ◦ Moderate: 100 < PaO_2/FiO_2 leq 200 mmHg ◦ Severe: PaO_2/FiO_2 leq 100$ mmHg
Alternative Settings (Proposed Updates): ◦ Non-intubated patients: Consider ARDS if PaO_2/FiO_2 leq 300 or SpO_2/FiO_2 leq 315 (if SpO_2 leq 97%) on high-flow nasal oxygen ≥ 30 L/min or NIV with PEEP ≥ 5 cmH2O. ◦ Intubated patients (S/F ratio): ◦ Mild: 235 < S/F leq 315 ◦ Moderate: 148 < S/F leq 235 ◦ Severe: S/F leq 148 (Note: S/F is SpO_2/FiO_2; used if SpO_2 leq 97%). ◦ Resource-limited settings: Consider ARDS if SpO_2/FiO_2 leq 315 (if SpO_2 leq 97%) without specific PEEP or flow requirements.

MANAGEMENT & TREATMENT¶

Mechanical Ventilation Strategy¶

Lung Protective Ventilation: ◦ Low Tidal Volume: Target 6 mL/kg of predicted body weight (PBW). ◦ Pressure Control: Target plateau pressure ≤30 cmH2O.
Recruitment & Positioning: ◦ High-PEEP or "open lung" strategy to improve oxygenation. ◦ Prone Position: Recommended for severe ARDS (PaO_2/FiO_2 < 150 mmHg) to reduce mortality. ◦ Recruitment Maneuvers: Use with caution; no clear benefit over high PEEP-FiO2 titration.
Pharmacotherapy: ◦ Glucocorticoids: Not recommended for routine use. ◦ Hydrocortisone: Low-dose may be considered in sepsis or severe pneumonia. ◦ Inhaled Vasodilators: (e.g., inhaled NO, inhaled epoprostenol) used to improve oxygenation.
Neuromuscular Blockade: ◦ Not for routine use; may increase survival in severe ARDS.

Fluid Management Algorithm¶

Initial Assessment: Identify non-COVID-19 ARDS.
Action: Initiate diuresis to reduce pulmonary edema.
Monitoring: Monitor blood pressure continuously during diuretic therapy.
Decision Point: Maintain Mean Arterial Pressure (MAP) ≥ 65 mmHg.
Outcome: If MAP ≥ 65 mmHg is maintained, continue diuresis; if hypoperfusion occurs, adjust management to ensure adequate perfusion.

PROGNOSIS & COMPLICATIONS¶

• Mortality Factors: ◦ Primarily driven by nonpulmonary causes (sepsis, organ failure). ◦ Age: Patients >75 years have ≈60% mortality; patients <45 years have ≈20% mortality. • Long-term Sequelae: ◦ Fibrotic Phase: Some patients develop permanent lung damage requiring long-term ventilation/oxygen. ◦ Complications of Fibrosis: Pulmonary hypertension, increased pulmonary dead space, and risk of pneumothorax.

KEY PEARLS & CLINICAL TRAPS¶

• Lung Protective Ventilation: Standard is 6 mL/kg PBW with plateau pressure ≤30 cmH2O. ◦ Prone Positioning: Specifically indicated for severe ARDS (PaO_2/FiO_2 < 150). ◦ Fluid Management: Goal is to minimize lung edema while maintaining MAP ≥ 65 mmHg. ◦ Glucocorticoids: Not routine; only used in specific subsets like sepsis or severe pneumonia. ◦ S/F Ratio: Used for intubated patients where SpO_2 leq 97%; Mild (235 < S/F leq 315), Moderate (148 < S/F leq 235), Severe (S/F leq 148).

Reference Tables¶

TABLE 312-1 Clinical Disorders Commonly Associated with¶

Harrison's 22e, p.2299

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¶

Harrison's 22e, p.2300

SEVERITY: OXYGENATIONa O	NSET	CHEST RADIOGRAPHb	ABSENCE OF LEFT ATRIAL HYPERTENSION
Mild: 200 mmHg < Pao/Fio ≤300 mmHg A 2 2 Moderate: 100 mmHg < Pao/Fio ≤200 i mmHg 2 2 s Severe: Pao/Fio ≤100 mmHg 2 2	cute: Within 1 week of a clinical nsult or new or worsening respiratory ymptoms	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, then some objective evaluation is required (e.g., echocardiography) to rule out hydrostatic edema

TABLE 312-3 Evidence-Based Recommendations for ARDS Therapies TREATMENT Mechanical ventilation¶

Harrison's 22e, p.2303

TREATMENT	RECOMMENDATIONa
Mechanical ventilation
Low tidal volume	A
Minimized left atrial filling pressures	B
High-PEEP or “open lung”	Bb
Prone position	Bb
Recruitment maneuvers	Cb
High-frequency ventilation	D
Early neuromuscular blockade (routine use)	Cb
Inhaled vasodilators (e.g., inhaled NO, inhaled epoprostenol)	C