23: Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome

Bashar M. Mourad1 and Keith M. Rose2

1 New York University School of Medicine, New York, NY, USA

2 Hackensack University Medical Center, Hackensack, NJ, USA


Definition of disease

  • ARDS is a life‐threatening clinical syndrome with heterogeneous underlying pathologic processes and is characterized by widespread lung inflammation resulting in bilateral alveolar infiltrates, atelectasis, and hypoxemia.
  • The American–European Consensus Conference first established clinical criteria for ARDS in 1994. This was the prevailing definition until the 2012 Berlin definition refined the definition and criteria to improve reliability and predictive validity.


  • The age‐adjusted incidence for patients with ARDS is 38.9 per 100 000 person‐years.
  • There has been a decline in hospital‐acquired ARDS with no change in incidence of admissions for ARDS.
  • The incidence of lung injury has been shown to increase with age.
  • Estimates suggest there are approximately 190 600 new cases annually in the USA.

Table 23.1 Etiologies of ARDS.

Direct Indirect
Aspiration (gastric contents, near drowning)
Lung contusion
Inhalation injury (smoke, toxins)
Embolism (amniotic, fat, air)
Severe sepsis
Non‐pulmonary trauma
Acute pancreatitis
Transfusion‐related acute lung injury (TRALI)
Massive transfusion
Burn injury
Drug overdose


  • ARDS is a clinical syndrome that represents a complex response to local and systemic inflammation with alveolar–capillary injury resulting in non‐cardiogenic pulmonary edema, atelectasis, and hypoxemia. The lung injury pathway can be triggered by a variety of primary diseases or processes. Causes can be categorized as direct or indirect pulmonary insults (Table 23.1).
  • The most common conditions associated with the onset of ARDS include sepsis, pneumonia, aspiration, and trauma.
  • Patients that develop ARDS as a result of a direct pulmonary injury have more severe reductions in lung compliance and may be less responsive to PEEP.


  • Regardless of the underlying etiology, an inflammatory response results in neutrophil accumulation in the circulation of the lung.
  • The neutrophils are recruited and migrate across the vascular endothelial and alveolar epithelial surfaces and become activated. This increases alveolar–capillary membrane permeability leading to non‐cardiogenic pulmonary edema, and atelectasis with a classic pathophysiology of diffuse alveolar damage.
  • This change in permeability allows flooding of alveoli and interstitial spaces with pro‐inflammatory cytokines (TNF‐α, IL‐1, IL‐8), reactive oxidative species, and protein‐rich fluid, resulting in edema and impairing gas exchange.
  • High concentrations of protein in the alveoli interfere with the ability of surfactant to keep alveoli open which results in atelectasis.
  • The clinical consequences of the ongoing lung injury include impaired oxygenation, decreased lung compliance, and increased pulmonary arterial pressure.
  • The progression of ARDS had been thought to evolve through three stages: the exudative phase, fibroproliferative phase, and recovery phase. However, recent evidence suggests that there is significant overlap with less discrete timing and phases.

Exudative phase (0–7 days)

  • This phase is characterized by continued accumulation in the alveoli of excessive fluid, protein, and inflammatory cells that have entered the air spaces from the alveolar capillaries.
  • Progressive atelectasis decreases the number of alveoli available for ventilation, contributing to worsening hypoxemia.
  • Intrapulmonary shunting occurs as more blood passes through the lungs without being oxygenated. This ultimately leads to refractory hypoxemia and low arterial oxygen pressure (PaO2) that does not improve despite increases in supplemental oxygen therapy (FiO2).
  • Hypoxemia is often the most profound during this phase.

Fibroproliferative phase (7–14 days)

  • Some patients achieve complete resolution of lung injury before progressing onto the fibroproliferative stage, whereas others progress directly to fibrosis.
  • The balance between pro‐inflammatory and anti‐inflammatory mediators is thought to be an important determinant of the overall inflammatory response, the extent of lung injury, and clinical outcomes.
  • The extent of fibrosis is also related to the severity of the initial injury, ongoing or repetitious lung injury, toxic oxygen effects, and ventilator‐associated lung injury.
  • Those struggling to recover often enter a fibrotic phase. As the inflammatory response continues, infiltration of fibroblasts leads to collagen deposition, and fibrosis. This results in stiff, poorly compliant lungs.
  • The degree of fibrotic changes is quite variable among patients with ARDS. Predominantly fibrotic changes can lead to prolonged ventilator dependency.
  • Prolonged ventilator dependency may necessitate tracheostomy and prolonged ventilator weaning. This decision is also based on the extent of other organ function and overall goals of care for each patient.

Recovery phase

  • For those patients who instead enter the recovery phase, there is deactivation of anti‐inflammatory cytokines produced by neutrophils.
  • Deactivated neutrophils undergo apoptosis and phagocytosis. This allows proliferation of type II alveolar cells with squamous metaplasia later resulting in type I alveolar cells, which helps re‐establish the epithelial lining of the alveoli.
  • This return of structural integrity creates an osmotic gradient, which draws fluid out of the alveoli and promotes resolution of pulmonary edema and atelectasis.
  • Oxygenation usually improves to the point of successful liberation from mechanical ventilation.

Predictive/risk factors

There are several diverse conditions associated with the onset of ARDS. Patients with the risk factors listed in Table 23.2 are at increased risk for development of ARDS.


Table 23.2 Risk factors for ARDS.

Risk factor Comments
Sepsis The inflammatory cascade that results in sepsis may be severe enough to result in lung injury that leads to ARDS
Alcoholism In the setting of sepsis, alcoholics are at much higher risk due to a predisposition to oxidative lung injury
Trauma Occurs more commonly in patients with bilateral lung contusions, and fat embolism following long bone fractures
Drug overdose Most commonly implicated drugs include aspirin, tricyclic antidepressants (TCAs), cocaine, opioids, and phenothiazines
TRALI Cytokine‐mediated process that occurs with any blood product transfusion including fresh frozen plasma, platelets, or packed red blood cells
Massive transfusion Most commonly in patients requiring transfusion of more than 15 units of red blood cells
Lung transplant Most at risk during the first week post lung transplant surgery due to primary graft failure. Attributed to imperfect preservation of the lung
Hematopoietic stem cell transplantation Occurs due to risk of infectious and non‐infectious complications


  • There is no standard screening process for ARDS, but early recognition is important.
  • Review a patient’s history to determine whether a risk or etiology is present, such as timing of a transfusion.
  • Check an ABG to determine the degree of hypoxemia based on a patient’s PaO2/FiO2 ratio.
  • Check a chest radiograph.
  • Check an echocardiogram to evaluate heart function and to rule out hydrostatic edema.

Primary prevention

  • There is no specific therapy to prevent ARDS. Primary prevention is in the form of standard of care treatment for a patient based on their underlying illness.
  • In patients who are already on ventilatory support for reasons unrelated to ARDS, low‐tidal volume ventilation (6–8 mL/kg PBW), PEEP, and lowest possible FiO2 have been shown to reduce the risk for ARDS.. These interventions prevent alveolar hyperinflation and cyclic stretching which can trigger lung injury.
  • A checklist that encompasses other best practice recommendations for lung injury prevention should be used to address other factors that may increase the risk for ARDS. This checklist includes:

    • Aspiration precautions, which includes elevating the head of the bed to 30°, gastric acid neutralization, and oral antiseptic hygiene.
    • Avoidance of excessive fluid administration in patients with shock.
    • Empiric antimicrobial treatment and infection source control based on site of infection and immune status.
    • Limiting blood, platelet, and plasma transfusions unless indicated (i.e. hemoglobin <7 g/dL or if actively bleeding).
    • Re‐evaluating non‐invasive ventilation use within 30 minutes of initiating it to prevent delay in intubation, if necessary.
    • Utilizing structured handoffs for at‐risk patients between providers when transferring patients to ICU.


Nov 20, 2022 | Posted by in ANESTHESIA | Comments Off on 23: Acute Respiratory Distress Syndrome

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