Direct Lung Injury

• Common causes: Bacterial pneumonia, Aspiration pneumonia
• Less Common: Viral pneumonia, Fat emboli, Inhalation injury, Near drowning, Pulmonary contusion

Indirect Lung Injury

• Common causes: Sepsis, Severe trauma or shock with multiple transfusions
• Less common: Blood product transfusions, Acute pancreatitis, Burns, Disseminated intravascular coagulation, Drug overdose, Head injury, Trauma

• Chronic alcoholism
• Advancing age
• Hypoproteinemia
• Cigarette smoking
• Chronic lung disease
• Acidemia
• Multiple predisposing conditions

1. Type I alveolar cells -- epithelial cells across which gas exchange occurs
2. Type II alveolar cells -- surfactant-producing cells

• Type I alveolar cells: damage leads to deposition of proteins, fibrin, and cellular debris --> hyaline membranes --> decrease lung compliance and decreased oxygenation capabilities
• Type II alveolar cells: decreased surfactant production --> alveolar collapse

Exudative Stage

damage to alveolar and vascular endothelium (both type I and type II alveolar cells) --> leakage of fluid, protein, and inflammatory cells into interstitial space and alveoli

Proliferative Stage

type II cells proliferate with some epithelial cell regeneration, fibroblastic reaction, and remodeling --> increased fibrosis with decreasing compliance

Fibrotic Stage

some patients progress to this irreversible phase of collagen deposition in alveolar, vascular, and interstitial beds --> chronic fibrotic changes --> decreased pulmonary function upon recovery of acute issues

Oxygenation

• ALI - PaO2/FiO2 < 300 mmHg
• ARDS - PaO2/FiO2 < 200 mmHg

Onset

• Acute -- within 72 hrs of hypoxemia and chest x-ray changes

Chest Radiography

• Bilateral infiltrates -- consistent with pulmonary edema

Cardiac Assessment

• No clinical evidence of left atrial hypertension or PCWP < 18 mmHg

• Fluid and Hemodynamic Management
• Lung-Protective Ventilation
• Nutrition
• Corticosteroids
• Beta-Adrenergic Agonists

• Main characteristics of ALI/ARDS = increase lung water
• Normal fluid balance in lung -- interaction of oncotic pressure and hydrostatic pressure
• Oncotic pressure reduced in ARDS -- edema can occur with relatively minimal changes in hydrostatic pressure
• Minimizing fluid administration can help reduce changes in hydrostatic pressure within blood vessels --> decreasing fluid shifts to extravascular spaces

• Low-tidal volume ventilation (6-8 ml/kg) = standard of care
• In ARDS -- injured portion of the lung is non-compliant and inflates poorly while the still healthy portions of the lung are still compliant and can overinflate and stretch excessively
• The overextension of the still healthy lung leads to spreading of lung damage and further progression of ARDS
• Pplat -- represents the pressure in the smaller airways and alveoli -- keeping the Ppat < 30 cm H2O protects the still healthy portions of the lung from overdistension and further injury
• Permissive Hypercapnea -- allowance of higher pCO2 levels (> 45 mmHg) and lower pH (< 7.35) values to achieve lower tidal volume ventilation

• N-3 polyunsaturated fatty acids (GLA and EPA) serve as precursors of eicosanoids which modulate the intensity and duration of the inflammatory response
• N-3 polyunsaturated fatty acids have been shown to decrease neutrophil migration, decrease production of reactive oxygen species, and decrease formation of inflammatory cytokines

• Currently not recommended for ALI/ARDS -- but if they are used, they must be used early on (higher risk of death found if steroids started > 13 days after ARDS onset)
• ARDS --> upregulation of inflammatory response (cytokines, macrophages, etc.)
• Corticosteroids inhibit numerous factors in the inflammatory pathway as well as increase anti-inflammatory mediators (IL-1 antagonists, IL-10, etc.)
• Thought to play a role in treating ongoing inflammation, cell proliferation, and abnormal collagen deposition found in persistent ALI/ARDS
• No change in overall mortality, but has shown improvement in oxygenation, shock-free days, and ventilator-free days

• Unproven treatment
• Stimulate resorption of pulmonary edema fluid by pumping fluid from the alveoli via Na+K+ ATPase pump --> decreased pulmonary fluid
• Found to help reduce inflammation and decrease pulmonary endothelial permeability
• Patients with ARDS can have increased airway resistance --> resistance can be decreased by the bronchodilating effects of beta-agonists either IV or inhaled

• Concurrent liver failure
• Long duration of mechanical ventilation
• Prolonged non-pulmonary organ failure
• Advanced age
• Low PaO2/FiO2
• High plateau pressures -- indicating lung compliances/stiffness
• Hypoproteinemia
• Length of hospitalization prior to ARDS