acute respiratory distress syndrome; acute lung injury (ARDS, ALI)

Introduction

ARDS is the most severe form of acute respiratory failure due to acute pulmonary injury. It is a diagnosis of exclusion.

Classification

• degree of hypoxemia:
  • mild (200 mm Hg < PaO2/FIO2 <= 300 mm Hg)*
  • moderate (100 mm Hg < PaO2/FIO2 <= 200 mm Hg)*
  • severe (PaO2/FIO2 <= 100 mm Hg)*
• 4 ancillary variables for severe ARDS:
  • radiographic severity
  • respiratory system compliance (<=40 mL/cm H2O)
  • positive end-expiratory pressure >= 10 cm H2O)
  • corrected expired volume per minute (>= 10 L/min)

* with PEEP > 5 cm H2O

Etiology

• direct pulmonary injury
  • pneumonia or other pulmonary infection (most important)
  • aspiration of gastric contents
  • major trauma: pulmonary contusion
  • near drowning
  • inhalation injury
    • mechanical ventilation
      • lower tidal volumes may reduce risk
• indirect pulmonary injury
  • sepsis, particularly from an abdominal source
  • hemorrhagic shock
  • drug overdose (heroin, methadone, barbiturates)
  • major trauma
    • multiple fractures
  • multiple blood transfusions
  • pancreatitis

Epidemiology

• incidence & mortality increases with age

Pathology

• disruption of the alveolar capillary membrane
• increased vascular permeability
• accumulation of neutrophils & protein rich edema in the alveolar space
• up to 70% of alveoli may be non-functional
• may be component of alveolar dead space
• a fibroproliferative stage may occur within 2 weeks of onset
  • loss of alveolar structures
  • obliteration of vasculature
  • interstitial infliltration of chronic inflammatory cells
  • deposition of type 1 collagen
  • severity of fibroproliferative reaction correlates with increased mortality
• varying degrees of multiorgan failure accompany ARDS

Clinical manifestations

• rapid onset
  • < 48 hours after precipitating event; < 1 week
  • generally < 24 hours
• severe dyspnea
• tachycardia
• tachypnea
• diffuse bilateral crackles on chest auscultation
• hypoxemic respiratory failure

Diagnostic criteria

• onset within 1 week of ARDS insult (most within 72 hours)
• bilateral lung opacities consistent with pulmonary edema
• acute respiratory failure unrelated to heart failure or volume overload
• PaO2/FiO2 of < 300 mm Hg on at least 5 mm PEEP
  • PaO2/FiO2 of 100-200 (moderate); < 100 mm Hg (severe)

Laboratory

• arterial blood gas (ABG)
  • hypoxemia, pO2/fiO2 < 200 mm Hg for ARDS
  • pO2/fiO2 < 300 mm Hg for acute lung injury
• pulse oximetry: SaO2 < 88%
• sputum for gram stain & culture (essential)

Diagnostic procedures

• hemodynamic monitoring
  • distinguish cardiogenic pulmonary edema from ARDS
  • pulmonary artery occlusion pressure < 18 mm Hg
  • not routinely recommended
• echocardiography
  • distinguish cardiogenic pulmonary edema from ARDS
• fiberoptic bronchoscopy with bronchoalveolar lavage &/or bronchoscopic biopsy is generally performed as indicated after CT

Radiology

• chest radiograph
  • diffuse bilateral pulmonary infiltrates
  • no pulmonary vascular redistribution (i.e. no heart failure)
  • no cardiomegaly
  • pleural effusions are rare in the absence of another condition predisposing to pleural effusion
• chest CT as indicated

Complications

• overall mortality 30-40% worldwide (50 countries)
  • mortality is 50% when associated with sepsis
• multiple organ dysfunction & secondary pulmonary infections may occur if the patient survives the acute phase
• delirium in the elderly

Differential diagnosis

• cardiogenic pulmonary edema
  • enlarged cardiac silhouette on chest X-ray
  • improvement with diuresis &/or afterload reduction
• diffuse alveolar hemorrhage
  • evidence of vasculitis, acute kidney injury, hematuria
  • hemosiderin-laden macrophages with bronchoalveolar lavage
  • associated with stem cell transplantation
• acute eosinophilic pneumonia
  • cough, fever, pleuritic chest pain, myalgia, precipitated by smoking
  • > 15% eosinophils in bronchoalveolar lavage fluid
• hypersensitivity pneumonitis
  • onset generally over weeks, course progressive
  • exposure history (farmers, birds, hot tubs)
• acute interstitial pneumonia
  • may be impossible to distinguish for ARDS
  • no inciting factors for ARDS
  • may responed to glucocorticoids
• pulmonary embolism unlikely if multifocal pulmonary opacities on chest X-ray

Management

• use high-flow nasal oxygen vs conventional oxygen therapy to reduce risk of intubation
  • noninvasive positive-pressure ventilation (NPPV) delivered via helmet may be alternative to mechanical ventilation
• mechanical ventilation
  • oxygenation
    • target partial pressure of oxygen 55-80 mm Hg NEJM
    • oxygen saturation levels titrated > 96% SaO2
    • no benefit in titration to > 97% SaO2
    • oxygen saturation titrated to 88-92% results in higher 90 day mortality (44% vs 30%)
  • PEEP of 5-12 cm H2O
    • 8 vs 13 cm H20 associated with similar outcomes
    • higher PEEP may reduce morbidity but not mortality
      • higher PEEP recommended for patients with moderate-to-severe ARDS
    • use lowest PEEP necessary to achieve SaO2 of 88% with FiO2 of < 60% without hypotension
    • individualizing PEEP with esophageal balloon-guided PEEP titration does not improve outcomes
  • lung protective ventilation (permissive hypercapnia)
  • peak inspiratory pressure < 30-35 mm Hg
  • end-expiratory pressure (plateau pressure) < 30 cm Hg
  • tidal volume 6 mL/kg IBW (4-8 mL/kg)
    • decrease tidal volume by 1 mL/kg as needed to keep plateau pressure < 30 cm Hg
    • low tidal volume ventilation is the only intervention shown to reduce mortality in patients with ARDS of any severity
    • low tidal-volume ventilation, prone positioning, & early neuromuscular blockade reduce mortality
  • recruitment maneuvers (PEEP of 40 cm of water for 40 seconds) of no benefit, PEEP of 45 cm of water for 2 minutes harmful
• prone positioning during mechanical ventilation (4-20 hours/day)
  • mortality benefit in patients with moderate-severe ARDS
  • >= 16 hours/day in prone position
  • may improve oxgenation decrease 28-day & 90-day mortality
  • begin prone positioning early in patients on low tidal-volume ventilation
  • prone positioning does not reduce the time to ECMO weaning in patients with severe ARDS
• recruitment maneuvers (short duration higher inspiratory pressure to open atelectatic alveoli) strongly discouraged.
• neuromuscular blockade may have a survival benefit in patients with moderate-severe ARDS
  • early treatment of patients with severe ARDS
    • partial pressure of oxygen [[[A448459|PaO2]]]:fraction of inspired oxygen [[[A3796|FiO2]]] <100) -l imit courses to 48 hours or shorter
  • cisatricurium besylate for 48 hours
  • mortality reduction at 28 days 24% vs 33%
  • more important than intravascular volume manangement
  • do not routinely use continuous infusion of neuromuscular blocking agent
  • no benefit to early neuromuscular blockade
• intravascular volume management
  • maintain lowest possible intravascular volume compatible with adequate tissue perfusion
    • limit IV fluid boluses
    • use diuretics to keep central venous pressure low
      • implement after off vasopressors for 12 hours
    • target central venous pressure = 4 mm Hg
  • conservative fluid management may have short-term benefit
  • no mortality benefit
• glucocorticoids
  • may be of benefit for adrenal insufficiency
    • hydrocortisone 50 mg IV every 6 hours + fludrocortisone 50 ug PO QD
  • glucocorticoids (no adrenal insufficiency)
    • may be of benefit in fibroproliferative phase
      • methyprednisolone 1 mg/kg IV started early & tapered over 28 days of benefit
    • may be of benefit for Covid-19 & community-acquired pneumonia
    • early high dose glucocorticoids of no benefit
      • number needed to harm = 3 (infection)
    • of no benefit for acute treatment of ARDS
• pulmonary artery catheter of no benefit
• venovenous extracorporeal membrane oxygenation (ECMO) of no benefit
  • recommended for patients with severe ARDS (PaO2:FiO2 <80 or pH <7.25 with PaCO2 >=60 mm Hg), low certainty of evidence
• unproven therapies
  • inotropic agents (unproven, controversial)
  • nitric oxide:
    • reduces pulmonary artery pressure & improves oxygenation
    • no improvement in mortality
    • not recommended
  • ketoconazole not recommended
  • surfactant not recommended
  • statin of no benefit
  • airway pressure release ventilation
  • IFN-beta-1a of no benefit
• any red cell transfusion may increase mortality

Prognosis:

• sepsis is most lethal form
• most survivors discharged to long-term care facility
• most survivors regain baseline lung function within 12 months

Notes

• non-standard care frequent in Europe

More general terms

• respiratory distress syndrome (RDS)
• acute respiratory failure

More specific terms

• electronic cigarette vaping-associated lung injury (VALI, EVALI)
• transfusion-related acute lung injury (TRALI)

Additional terms

• neonatal respiratory distress syndrome (hyaline membrane disease, neonatal RDS)

Patient information

acute respiratory distress syndrome (ARDS) patient information