Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS): Causes, Symptoms, Diagnosis & Management

 Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS): Causes, Symptoms, Diagnosis & Management

Acute Lung Injury and the Acute Respiratory Distress Syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening forms of acute pulmonary edema. Initially, ALI and ARDS were considered different stages of severity, with ALI representing a less severe form than ARDS. However, the overlap between the two conditions is substantial, and many experts no longer consider the distinction clinically important.

Although hypoxemia is the primary physiological abnormality, most patients die from the underlying cause such as sepsis or from complications like multiorgan failure rather than from refractory hypoxemia alone.

Current therapy for ALI/ARDS focuses on treating the underlying cause while applying pressure-targeted mechanical ventilation strategies with low tidal volumes and appropriate fluid management to prevent further lung injury.

The diagnosis should be considered when the following conditions are present:

A suitable clinical context with a likely underlying cause.

Bilateral alveolar or interstitial infiltrates appearing acutely (within 72 hours) on chest radiograph.

A ratio of arterial oxygen pressure (PaO₂) to fraction of inspired oxygen (FiO₂) of ≤300 mm Hg.

No clinical evidence that left ventricular failure or intravascular volume overload is the primary cause of pulmonary infiltrates.

Causes of Acute Lung Injury / ARDS

ALI/ARDS can result from direct lung injury or indirect systemic insults.

Direct causes

Direct lung injury includes pneumonia, aspiration of gastric contents, inhalation injuries, blunt chest trauma, near drowning, and toxic inhalations.

Indirect causes

Indirect causes occur when systemic inflammation damages the lungs through the circulation. These include sepsis, severe traumatic shock, large-volume blood transfusions (typically more than 15 units), pancreatitis, and reperfusion injury following cardiopulmonary bypass surgery.

Among all causes, sepsis is the most common, followed by pneumonia and aspiration.

Pathogenesis of ARDS

The development of ARDS begins with a pulmonary or systemic insult that triggers an inflammatory response in the lungs. This inflammation increases pulmonary capillary permeability and results in non-cardiogenic pulmonary edema.

The disease typically progresses through three phases:

1. Exudative Phase

This phase occurs immediately and usually lasts 3–7 days. It is characterized by diffuse alveolar damage with accumulation of fluid, proteins, and inflammatory cells within alveoli and interstitial spaces. Hyaline membranes form, type I alveolar cells undergo necrosis, and intra-alveolar hemorrhage may occur. These changes lead to decreased lung compliance, impaired ventilation, intrapulmonary shunting, and increased work of breathing. Mechanical ventilation with high oxygen concentration and positive airway pressure is often required.

2. Proliferative Phase

This phase overlaps with the late exudative phase and lasts 2–3 weeks. During this period, type II pneumocytes proliferate, alveolar edema begins to clear, and gas exchange gradually improves. Many patients can be liberated from mechanical ventilation during this stage.

3. Fibrotic Phase

Some patients progress to a fibrotic stage after several weeks. This phase involves progressive fibrosis of the lung interstitium and alveoli. Patients may develop emphysematous bullae and prolonged ventilator dependence, which increases morbidity and mortality.

Conditions That Can Mimic ARDS

Several diseases may present with similar radiologic findings and should be excluded before diagnosing ARDS. These include cardiogenic pulmonary edema, diffuse alveolar hemorrhage, acute interstitial pneumonia, Hamman-Rich syndrome, acute eosinophilic pneumonia, miliary tuberculosis, cryptogenic organizing pneumonia, and disseminated cancer.

Mechanical Ventilation in ALI/ARDS

Management of ALI/ARDS often requires mechanical ventilation using lung-protective strategies.

Patients with acute hypoxic respiratory failure and bilateral pulmonary infiltrates should be evaluated for ARDS. If left heart failure is suspected, cardiogenic pulmonary edema should be ruled out using clinical signs, pulmonary capillary wedge pressure measurements, Doppler ultrasound findings, or echocardiography.

Once ARDS is confirmed, predicted body weight (PBW) is calculated using the patient’s height. For men, PBW equals 50 + 2.3 × (height in inches − 60). For women, PBW equals 45.5 + 2.3 × (height in inches − 60).

Mechanical ventilation is typically initiated in assist-control mode with a tidal volume of 6 mL/kg predicted body weight, a positive end-expiratory pressure (PEEP) of about 5 cm H₂O, and a respiratory rate of up to 35 breaths per minute.

The ventilation goals are to maintain a PaO₂ between 55 and 80 mm Hg or oxygen saturation above 88%, keep plateau pressure below 30 cm H₂O, maintain FiO₂ below 0.6, and keep arterial pH between 7.30 and 7.45.

If plateau pressure exceeds 30 cm H₂O, tidal volume should be decreased by 1 mL/kg until pressures fall to acceptable levels, sometimes as low as 4 mL/kg. If plateau pressure remains low and tidal volume is below 6 mL/kg, tidal volume may be gradually increased. PEEP should be adjusted to maintain adequate oxygenation while minimizing FiO₂.

If acidosis occurs, the respiratory rate may be increased. Severe acidosis may require buffering agents such as sodium bicarbonate.

Oxygenation Strategy

To maintain adequate oxygenation, combinations of FiO₂ and PEEP are used. Lower FiO₂ values (0.3–0.4) typically require PEEP levels of 5–8 cm H₂O, whereas higher FiO₂ levels (0.8–1.0) may require PEEP levels of 14–23 cm H₂O.

Some clinicians prefer higher PEEP levels during the first 48–96 hours of ARDS if plateau pressures remain within acceptable limits.

Rescue Therapies

When severe hypoxemia persists despite optimal ventilation, rescue therapies may be used. These include inhaled vasodilators such as epoprostenol, nitric oxide, or iloprost, as well as prone positioning. Prone positioning improves oxygenation by redistributing ventilation and perfusion but should not be used in patients with open abdominal wounds, unstable fractures, spinal instability, or increased intracranial pressure.

Other advanced rescue strategies include inverse-ratio ventilation, high-frequency ventilation, and extracorporeal membrane oxygenation (ECMO).

Steroid Therapy

Corticosteroids may be used in selected patients with early ARDS. Treatment typically begins within the first 72 hours using methylprednisolone at 1 mg/kg intravenously, followed by a continuous infusion for up to 14 days. If no clinical or radiologic improvement occurs within 3–5 days, therapy should be discontinued. If improvement occurs, the dose is gradually tapered over several weeks.

Steroids initiated after 14 days of ARDS generally provide little benefit and may increase mortality.

Fluid Management

Fluid management plays an important role in ARDS treatment. Continuous monitoring of central venous pressure (CVP) and mean arterial pressure (MAP) is recommended. Adequate perfusion should be maintained with a MAP above 60 mm Hg.

If urine output is low and signs of poor circulation are present, inotropic support such as dobutamine may be required. If fluid overload occurs, diuretics such as furosemide may be administered to reduce pulmonary edema. Conservative fluid strategies have been shown to reduce the duration of mechanical ventilation and ICU stay without increasing mortality.

Long-Term Outcomes

Patients surviving ALI/ARDS often require prolonged intensive care. The average ICU stay is approximately 25 days, and many patients lose around 18% of their body weight during hospitalization. At one year, many survivors experience persistent functional limitations due to muscle wasting and weakness.

However, lung volumes and spirometry usually return to near normal within 6 months to 1 year, and most patients do not require long-term supplemental oxygen.

Summary

Acute lung injury and ARDS are severe forms of non-cardiogenic pulmonary edema characterized by diffuse lung inflammation and impaired gas exchange. Management focuses on treating the underlying cause, using lung-protective mechanical ventilation with low tidal volumes, applying conservative fluid strategies, and considering early corticosteroid therapy. Rescue therapies may be necessary for patients with refractory hypoxemia. Although survival has improved with modern management strategies, many survivors experience long-term physical limitations.