Overview

• Acute respiratory distress syndrome (ARDS) occurs when the alveoli fill with fluid, which impairs gas exchange.
• Characterized by acute dyspnea, hypoxemia, and pulmonary infiltrates.
• Can lead to reduced lung compliance, increased pulmonary dead space, increased risk of pneumothorax, and pulmonary hypertension.
• ARDS has a mortality rate of approximately 40%.
• Treatment for acute respiratory distress syndrome requires treatment of the underlying causes.
• Mechanical ventilation restores airflow, but beware of potential complications, including: volutrauma (overdistention of the alveoli), alectectrauma (alveolar strain from repeated opening and closing), and, biotrauma (from migration of pro-inflammatory molecules and pathogens).
• Treatment includes fluid management measures, such as diuretics, to reduce left atrial filling pressure; some also recommend the use of neuromuscular blockades.
• Newborn respiratory distress syndrome (aka, infant respiratory distress syndrome, respiratory distress syndrome of the newborn) occurs when there is inadequate production of surfactant by premature lungs, leading to alveolar collapse; thus, treatment includes administration of synthetic surfactant and oxygen support. The risk of neonatal respiratory distress correlates with the degree of prematurity.

Pathophysiology: 3 stages
Exudative Phase: The initial response to injury, and occurs within the first 7 days after exposure.

• Inflammation damages the capillary endothelium and alveolar epithelium, and increases the permeability of these layers. We show neutrophils and their pro-inflammatory cytokines, but be aware that other cells of the innate immune system also play a role in barrier injury.

• Protein-rich fluid, activated neutrophils, and other pro-inflammatory mediators and cellular debris pass through the barrier and fill the alveolus.
• These infiltrating proinflammatory mediators damage the epithelial lining of the alveolus, leaving the basement membrane “denuded.”
• Furthermore, due to the loss of alveolar epithelial cells, surfactant production and fluid resorption is inhibited,which compounds fluid retention.
• Hyaline membranes from along the denuded basement membranes; these are formed by accumulating cellular debris and fibrin.
• The coagulation cascade is triggered by capillary endothelial damage, which leads to the formation of microthrombi in the vessels.
• As a result of these pathological processes, gas exchange is inhibited, dead space is increased, pulmonary hypertension occurs, and lung compliance decreases.

Proliferative Phase: barrier repair and fluid resorption and occurs days 7-21 after exposure to pulmonary injury.

• The alveolar epithelium and capillary endothelium barriers are re-established.
• Thus, surfactant production and fluid reabsorption resume
  – Epithelium sodium channels and aquaporins are inserted in the alveolar epithelium, and move fluids to the interstitium.
• Macrophages and lymphocytes remove apoptotic and inflammatory mediators, thus reducing further harm to the epithelia.
• As part of the healing and rebuilding process, fibroblasts and other interstitial cells proliferate to form a provisional extracellular matrix, which will eventually be removed by matrix metalloproteinases.
• However, in some individuals, pro-inflammatory and fibrotic forces overwhelm the healing and clearance process.

Fibrotic Phase: Fibrosis

• Extensive epithelial damage trigger over-proliferation and differentiation of fibroblasts and deposition of collagen, which leads to tissue fibrosis and destruction of the microvasculature.
• Thus, pulmonary dysfunction continues.

Causes of ARDS

• Direct and indirect causes of lung injury lead to acute respiratory distress.
• The most common causes are pneumonia (direct) and sepsis(indirect)
  – Account for more than half of all ARDS cases.
• Additional Direct Causes:
  – Aspiration of gastric contents
  – Pulmonary contusion
  – Near drowning
  – Vaping.
  Be aware that lung injury caused by vaping is sometimes called “EVALI” – “E-cigarette or Vaping Associated Lung Injury”, and is particularly associated with vaping fluids containing Vitamin E acetate (Vitamin E acetate is used in THC vaping products).
• Additional Indirect Causes:
  – Trauma
  – Repeated blood transfusion
  – Pancreatitis
  – Drug reactions or overdoses (ex: various narcotics, aspirin, tricyclic antidepressants).

Berlin Definition of ARDS
Establishes diagnostic criteria

• Onset of signs and symptoms must be *within the last 7 days of known clinical insult, with new or worsening symptoms during the last week.
• Chest X-ray or CT will show bilateral opacities consistent with pulmonary edema.
• Respiratory failure cannot be otherwise fully explained by cardiac failure or fluid overload.
• Presence of acute hypoxemia.
  – Based on the ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) (assessed while the patient is on a ventilator with a positive-end expiratory pressure (PEEP) of 5 or greater cm H2O).
  – Hypoxemia severity can be categorized as mild (201-300 mmHg); moderate (101-200 mmHg), or severe (100 mmHg or less).