What is Acute Respiratory Distress Syndrome (ARDS)?

Acute Respiratory Distress Syndrome (ARDS)

Acute Respiratory Distress Syndrome (ARDS) is a devastating critical illness characterized by acute inflammatory lung injury with bilateral pulmonary infiltrates, impaired oxygenation, and high mortality of approximately 30-40%, requiring lung-protective ventilation strategies as the cornerstone of management. 1, 2

Definition and Diagnostic Criteria

ARDS is defined by the Berlin criteria, which include:

• Timing: Onset within one week of a known clinical insult or new/worsening respiratory symptoms
• Imaging: Bilateral opacities on chest radiography not fully explained by effusions, collapse, or nodules
• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload
• Oxygenation impairment: PaO₂/FiO₂ ratio ≤300 mmHg with minimum PEEP of 5 cmH₂O 1, 2, 3

Severity Classification:

• Mild ARDS: 200 mmHg < PaO₂/FiO₂ ≤ 300 mmHg
• Moderate ARDS: 100 mmHg < PaO₂/FiO₂ ≤ 200 mmHg
• Severe ARDS: PaO₂/FiO₂ ≤ 100 mmHg 3

Pathophysiology

ARDS develops when pulmonary or extrapulmonary insults trigger an inflammatory cascade characterized by:

• Leukocyte infiltration and local immune activation
• Alveolar endothelial and epithelial injury
• Increased pulmonary vascular permeability
• Development of acute pulmonary edema
• Loss of aerated lung tissue 1

This leads to:

• Impaired gas exchange
• Decreased lung compliance
• Ventilation-perfusion mismatch
• Refractory hypoxemia 1, 4

Etiology

ARDS can be triggered by various insults, with sepsis being the most common cause (accounting for approximately 40% of cases). Other common causes include:

• Pneumonia
• Aspiration
• Trauma
• Pancreatitis
• Transfusion-related acute lung injury
• Drug overdose
• Inhalation injury 1, 4

Pulmonary and intra-abdominal infections are the most commonly associated sites of infection in sepsis-related ARDS 1.

Management

Ventilation Strategies

Lung-protective ventilation is the cornerstone of ARDS management:

• Low tidal volumes: 4-8 mL/kg predicted body weight
• Plateau pressure limit: <30 cmH₂O
• Driving pressure monitoring: Plateau pressure - PEEP
• Permissive hypercapnia: Accept higher PaCO₂ levels to avoid ventilator-induced lung injury (target pH >7.2) 2, 3

PEEP Titration Based on ARDS Severity

Severity	PaO₂/FiO₂	Recommended PEEP
Mild	201-300 mmHg	Lower PEEP (5-10 cmH₂O)
Moderate	101-200 mmHg	Higher titrated PEEP
Severe	≤100 mmHg	Higher titrated PEEP with consideration for prone positioning and neuromuscular blockade [2]

Adjunctive Therapies

• Prone positioning: Significantly improves mortality in severe ARDS (PaO₂/FiO₂ <150 mmHg) 2, 3
• Conservative fluid management: Reduces ventilator and hospital days in patients without shock 5
• Neuromuscular blockade: May reduce mortality in selected patients with severe ARDS 2, 5
• Extracorporeal membrane oxygenation (ECMO): Consider for refractory hypoxemia in severe ARDS when strict criteria are met 6, 5

Complications and Outcomes

• Mortality: In-hospital mortality remains high at 30-40%, with higher rates in severe ARDS 1, 3
• Cause of death: Most often due to unresolved sepsis or multisystem organ failure rather than progressive respiratory failure 1
• Long-term sequelae: Survivors often experience diminished functional capacity, mental health issues, and decreased quality of life 4

Monitoring and Prevention of Complications

• Monitor for ventilator-induced lung injury (barotrauma, volutrauma, atelectrauma)
• Implement prophylaxis for stress ulcers and venous thromboembolism
• Provide appropriate nutritional support
• Treat the underlying cause 2, 4

Emerging Concepts

Recent research has highlighted the heterogeneity of ARDS on aetiological, physiological, and biological levels, suggesting that precision medicine approaches may be needed for more effective treatments 1. Despite numerous trials of pharmacologic agents targeting inflammation, coagulation, oxidative stress, and endothelial injury, none have shown consistent benefit, and management remains primarily supportive 1, 3.

The failure of these targeted treatments may be partly due to insufficient understanding of the heterogeneity within ARDS, emphasizing the need for deeper phenotyping to identify specific endotypes that might respond to particular interventions 1.