Acute Respiratory Distress Syndrome in Adults

Key Points

• Acute respiratory distress syndrome is severe and often fatal acute respiratory failure; characterized by diffuse inflammatory lung injury rapidly progressing to increased pulmonary vascular permeability, increased lung weight, and hypoxemia
• Most commonly secondary to pneumonia, nonpulmonary sepsis, and trauma. Worsening respiratory status most commonly develops within 1 week of clinical insult ^r1
• Primary diagnostic tools are arterial blood gas levels showing hypoxemia with a PaO₂ to FiO₂ (fraction of inspired oxygen) ratio of 300 mm Hg or less and radiograph showing bilateral opacities; echocardiography may be required to ascertain that these opacities are not attributable to cardiogenic pulmonary edema ^r1
• Treatment is primarily conventional mechanical ventilation using lung-protective strategies (ie, low-tidal-volume and/or low-pressure ventilation) and a high concentration of inspired oxygen and PEEP
• Other supportive care measures include prone positioning during mechanical ventilation, conservative fluid management strategies, and provision of enteral nutrition to prevent respiratory muscle weakness
• Additional treatments focus on addressing underlying cause
• High mortality rate of up to 46%; survivors commonly have residual lung damage ^r1r2

Pitfalls

• Early stages can be difficult to differentiate from cardiogenic pulmonary edema, possibly resulting in delay of critical interventions ^r3
• An outbreak of lung injury associated with vaping was identified by CDC in September 2019; be aware that severe lung disease, including acute respiratory distress syndrome, can occur ^r4r5

Clinical Clarification

• Acute respiratory distress syndrome is severe and often fatal acute respiratory failure; characterized by diffuse inflammatory lung injury rapidly progressing to increased pulmonary vascular permeability, increased lung weight, and hypoxemia
• Preceded by a clinical insult—usually pneumonia, nonpulmonary sepsis, aspiration of gastric contents, or trauma
• Berlin definition of acute respiratory distress syndrome includes presence of all following criteria: ^r1r6
  • Timing of acute onset of symptoms (or worsening of nonacute symptoms) within 1 week of a known clinical insult
  • Hypoxemia as shown by the PaO₂ to FiO₂ (fraction of inspired oxygen) ratio of 300 mm Hg or less with PEEP or CPAP of 5 cm H₂O or greater
  • Chest imaging showing bilateral opacities that are not explained by effusions, atelectasis, or nodules, and are not cardiogenic in nature
  • Respiratory failure or pulmonary edema not fully explained by cardiac failure or fluid overload

Classification

• Under conventional mechanical ventilation, the following apply:
  • The 3 categories of acute respiratory distress syndrome are based on degree of hypoxemia, as shown by the PaO₂ to FiO₂ (fraction of inspired oxygen) ratio: ^r1r6
    • Mild: 200 mm Hg < PaO₂/FiO₂ ≤ 300 mm Hg
    • Moderate: 100 mm Hg < PaO₂/FiO₂ ≤ 200 mm Hg
    • Severe: PaO₂/FiO₂ ≤ 100 mm Hg
  • A minimum PEEP of 5 cm H₂O is required to make the severity classification; it may be delivered noninvasively with CPAP to classify mild cases ^r1r6

Clinical Presentation

Causes and Risk Factors

Diagnostic Procedures

Differential Diagnosis

Less common

• Chronic interstitial lung diseases (eg, idiopathic pulmonary fibrosis, occupational lung diseases, autoimmune diseases) ^c81c82c83c84
  • Clinical indicators
    • Dyspnea and cough slowly progressing over months or years, caused by diffuse alveolar damage
      • However, chronic interstitial lung diseases may sometimes worsen rapidly, mimicking acute respiratory distress syndrome
    • Associated signs and symptoms of the underlying disease (eg, arthralgias or arthritis in autoimmune disease)
    • Early radiographs may show subpleural reticular changes mixed with alveolar opacities
  • Differentiating features
    • Slower, progressive onset
    • Will not meet Berlin definition^r1
    • CT scan may suggest diagnosis
    • Lung tissue biopsy confirms diagnosis
• Acute interstitial pneumonitis ^c85d1
  • Clinical indicators
    • Rapid onset of respiratory failure, which clinically mimics acute respiratory distress syndrome symptomatically and radiologically, but for which no precipitating factor is identified
  • Differentiating features
    • Difficult to differentiate; can be thought of as idiopathic acute respiratory distress syndrome
• Malignancy ^c86d2
  • Clinical indicators ^d3
    • Rapid, progressive cancer disseminating throughout the lungs may have a presentation similar to that of acute respiratory distress syndrome
    • Usually lymphoma or acute leukemia
  • Differentiating features
    • Will not meet Berlin definition^r1
    • Bronchoalveolar lavage may reveal malignant cells
• Diffuse alveolar hemorrhage ^c87
  • Clinical indicators
    • Syndrome presenting with hemoptysis (two-thirds of patients) evolving over days to weeks with progressive anemia, diffuse alveolar infiltrates, and hypoxemic respiratory failure
    • Most commonly associated with underlying connective tissue disorder and less commonly with toxin inhalation or drug reaction
  • Differentiating features
    • Often requires serial bronchoalveolar lavage for diagnosis because symptoms and imaging findings are nonspecific
      • Hemoptysis is absent in one-third of patients and those patients may be indistinguishable from patients with acute respiratory distress syndrome
      • Intra-alveolar RBCs appear in lavage fluid in increasing numbers, with hemosiderin-laden macrophages appearing within 48 to 72 hours
      • CBC shows progressive anemia

Goals

• Maintain oxygenation via mechanical ventilation with adjustments of FiO₂ (fraction of inspired oxygen) and PEEP; ARDS Network goal is PaO₂ of 55 to 80 mm Hg or SpO₂ of 88% to 95% ^r15
• Avoid ventilator-induced lung damage by using protective (ie, volume-limited and/or pressure-limited) ventilator settings
• Maintain a neutral or net-negative fluid balance in hemodynamically stable patients
  • Central venous pressure goal of 4 to 8 mm Hg ^r16
  • Urine output of more than 0.5 mL/kg ^r16
  • Adequate cardiac output ^r16
• Identify and treat or reverse the underlying cause

Disposition

Treatment Options

Mainstay of treatment is supportive care in an ICU setting

• Mechanical ventilation
  • Most patients are managed with invasive mechanical ventilation (via an endotracheal tube or tracheostomy) using PEEP and a lung-protective strategy of low tidal volumes and airway pressures to mitigate ventilator-induced lung injury ^r17r18r19
  • Prone positioning improves mortality in severe cases and should be used as an upfront management strategy rather than as a rescue effort ^r20r21r22
  • Combination of low tidal volumes with prone ventilation is associated with the greatest reduction in mortality in moderate-to-severe acute respiratory distress syndrome ^r23
  • Minority of patients may be managed with noninvasive ventilation (eg, high-flow oxygen via nasal cannula [humidified oxygen with flow rates ≥20 L/min]) or CPAP or BPAP ventilation via mask or helmet ^r16r24r25
  • Venovenous extracorporeal membrane oxygenation is commonly used as rescue therapy for patients with refractory hypoxemia ^r18
    • Consider in patients with severe acute respiratory distress syndrome and hypoxemia (PaO₂/FiO₂ [fraction of inspired oxygen] less than 80 mm Hg), or severe hypercapnic respiratory failure (pH less than 7.25 with a PaCO₂ of 60 mm Hg or greater) that is refractory to optimal conventional management (including a trial of prone positioning) ^r26
    • Improved oxygenation, but limited data on effect on mortality; one study reported a significantly lower 28-day mortality compared with lung-protective ventilation ^r18r21
• Fluid management
  • Fluid management strategies to optimize oxygenation and maintain effective tissue perfusion include use of IV crystalloids, vasopressors (eg, norepinephrine), inotropes (eg, dobutamine), and diuretics (eg, furosemide)
  • Conservative fluid management results in more ventilator-free days and fewer days in the ICU compared with liberal fluid management ^r27r28
    • In some cases it may be reasonable to combine a liberal strategy (ie, for resuscitation early in course of disease) with a conservative strategy (ie, later in course of disease) ^r28
    • Pulmonary artery catheter–guided fluid management is associated with more complications than central venous catheter–guided management and does not improve outcomes; a pulmonary artery catheter should not be routinely used ^r29
• Pharmacological therapies
  • Corticosteroids
    • Administer corticosteroids if indicated for treatment of underlying condition (eg, COVID-19, septic shock, community acquired pneumonia, or steroid-responsive conditions)
      • NIH COVID-19 treatment guidelines recommend use of dexamethasone in hospitalized patients who require supplemental oxygen with or without mechanical ventilation ^r30
      • Corticosteroid therapy has been reported in many cases to be useful in vaping-related lung injury ^r7r31
    • Role for corticosteroids in other patients with acute respiratory distress syndrome is controversial and use is variable
      • Systematic reviews and meta-analyses show treatment with corticosteroids may reduce mortality and shorten the duration of mechanical ventilation ^r32r33
      • Optimal regimen and dosage has not been established; however, methylprednisolone is commonly used ^r34
      • Do not use corticosteroids for acute respiratory distress syndrome caused by influenza as may be associated with increased mortality in this subset of patients ^r32
  • Inhaled pulmonary vasodilators ^r35
    • Inhaled nitric oxide or prostaglandins are not routinely indicated
    • May improve oxygenation transiently in patients with severe hypoxemia; however, have not been shown to reduce morbidity or mortality ^r36
• Supportive therapies
  • Sedatives ^r37
    • Typically administered for patient comfort and safety
    • Guidelines recommend using either dexmedetomidine or propofol to achieve light levels of sedation in adults receiving mechanical ventilation and continuous sedation ^r37
  • Neuromuscular blockade
    • Addition of neuromuscular blockade during mechanical ventilation has been considered as a strategy for moderate to severe acute respiratory distress syndrome ^r38
      • Benefits of neuromuscular blockade include reduced patient–ventilator dyssynchrony, reduced work of breathing, and reduced accumulation of alveolar fluid ^r39
      • However, prolonged administration of neuromuscular blocking agents is associated with later neuromuscular weakness and requires deeper sedation, which can have negative consequences (eg, delirium, coma, long-term cognitive impairment)^r37r39
      • Large multicenter trial reported early administration of a 48-hour infusion of neuromuscular blockade with deep sedation in patients with moderate to severe acute respiratory distress syndrome resulted in lower mortality than deep sedation without routine neuromuscular blockade ^r40
      • Recent study conducted among patients with moderate to severe acute respiratory distress syndrome who were treated with a high-PEEP strategy demonstrated no significant difference in 90-day mortality between patients who received an early continuous neuromuscular blockade and those who were treated with a usual-care approach with lighter sedation targets ^r39
  • Other supportive care, including nutrition and prophylaxis of expected medical complications (eg, deep venous thrombosis, stress ulcers) ^r41

Monitoring

• Continuously monitor blood pressure, pulse oximetry, temperature, and respiratory rate (from ventilator) ^c105c106c107
• Frequently monitor arterial blood gas ^c108
• Central venous pressure monitoring is not mandatory but can assist with fluid management; pulmonary artery catheter is not indicated ^c109

Complications

• Common complications that occur in an ICU setting include the following:
  • Ventilator-induced lung injury, especially pulmonary edema ^c110c111
  • Ventilator-associated barotrauma (eg, pneumothorax, subcutaneous edema) ^c112c113c114
  • Ventilator-associated pneumonia ^r6c115
  • Catheter-related infections ^c116
  • Poor nutrition and loss of muscle mass ^c117c118
  • Deep vein thrombosis ^c119
  • Gastrointestinal bleeding ^c120
  • Delirium ^r40c121
• Pulmonary fibrosis develops in roughly two-thirds of patients with acute respiratory distress syndrome; patient may become increasingly reliant on persistent mechanical ventilation ^r64c122
• Cognitive impairment (post-intensive care syndrome) is common (70%-100% at hospital discharge, 46%-80% at 1 year, and 20% at 5 years) ^{r18r65r66c123}
• Depression and posttraumatic stress disorder are common ^r66c124c125
• Long-term physical disability and neuromuscular weakness ^{r18r65c126c127}

Prognosis

• No specific biomarker is considered predictive of outcome ^r53
• Mortality outside of a clinical trial setting remains high and relatively unchanged since the original consensus definition was developed in 1994 ^r18r67
  • Mild acute respiratory distress syndrome is associated with 34.9% mortality ^r2
  • Moderate disease is associated with 40.3% mortality ^r2
  • Severe disease is associated with 46.1% mortality ^r2
  • Highest risk of death is when sepsis is the underlying cause; trauma-related cases have a lower mortality rate than those unrelated to trauma ^r54

Screening ^c128

Prevention ^c129

• No evidence exists for effective preventive measures specific to this syndrome; however, practices likely to decrease risk include: ^r68
  • Primary prevention of nosocomial pneumonia
  • Primary prevention of aspiration ^c130
  • Appropriate antibiotic use
  • Restrictive use of blood transfusions ^c131
  • Avoid vaping and e-cigarette use ^r5c132c133d5
    • If continuing e-cigarette use or vaping
      • Do not use devices purchased from sources other than authorized retailers
      • Do not modify devices or use devices modified in any manner not intended by the manufacturer
      • Only use substances sold by an authorized manufacturer
      • Do not use products that contain THC (tetrahydrocannabinol)