How long does Respiratory Distress Syndrome (RDS) progress?

Respiratory Distress Syndrome Progression Timeline

Respiratory Distress Syndrome (RDS) progresses through three distinct phases over days to weeks: early exudative phase (days 1-5), fibroproliferative phase (days 6-10), and fibrotic phase (after day 10). 1

Pathophysiological Progression

Early Exudative Phase (Days 1-5)

• Initial pathological abnormalities include interstitial swelling, proteinaceous alveolar edema, hemorrhage, and fibrin deposition 1
• Basement membrane disruption and denudation, especially of alveolar epithelial cells, can be seen with electron microscopy 1
• After 1-2 days, hyaline membranes (sloughed alveolar cellular debris mixed with fibrin) are commonly observed 1
• Cellular infiltrates may be minimal or dominated by neutrophils, with fibrin thrombi visible in some alveolar capillaries and small pulmonary arteries 1
• Clinically presents with severe dyspnea, tachypnea, and unremitting hypoxemia 1

Fibroproliferative Phase (Days 6-10)

• Type II alveolar cells (surfactant-producing cells) proliferate and differentiate into new type I cells to reline alveolar walls 1
• Most alveolar edema resolves during this phase 1
• Hyaline membranes become less prominent 1
• Mononuclear cells replace the neutrophilic infiltrate 1
• Fibroblasts begin proliferating within the interstitium and depositing new collagen 1

Fibrotic Phase (After Day 10)

• Characterized by chronic fibrotic changes along the alveolar interstitium 1
• May not resolve for months in some cases 1
• Sustained or worsening pulmonary hypertension reflects the degree of fibrosis and obliteration of the vascular bed 1
• Poor prognosis is associated with late pulmonary hypertension in ARDS, likely reflecting severity of fibrosis 1

Clinical Course and Outcomes

• When clinical manifestations of sepsis-related RDS first appear, 28-33% of patients meet criteria for ARDS 1
• Surfactant therapy significantly reduces mortality rates, especially in infants less than 30 weeks' gestation or with birth weights less than 1250g 1
• Early rescue surfactant treatment (within 2 hours of birth) compared to delayed treatment shows decreased risks of:
  • Mortality (16% reduction) 1
  • Air leak (39% reduction) 1
  • Chronic lung disease (31% reduction) 1
  • Combined outcome of chronic lung disease or death (17% reduction) 1

Important Considerations

Pulmonary Mechanics

• Lung compliance approaches 20 ml/cmH2O in early ARDS, less than one-fourth that of normal 1
• Volume of aeratable lung is reduced by alveolar edema and surfactant dysfunction, accounting for higher inflation pressures 1
• Pulmonary resistance in infants with chronic lung disease is more than twice that of control subjects 1

Long-term Outcomes

• In children who had RDS as infants, airway obstruction and hyperreactivity can persist into childhood and early adult life 1
• Follow-up studies of children 6-15 years of age who had RDS show reductions in vital capacity and FEV1 (about 80% of control subjects) 1
• The pattern is obstructive, with low FEV/VC ratio and high ratio of residual volume to total lung capacity 1

Treatment Considerations

• Multiple doses of surfactant have shown decreased mortality (13% vs 21%) compared to single-dose treatment 2
• Pneumothorax rates are also significantly lower with multiple-dose surfactant therapy (9% vs 17%) 2
• The INSURE strategy (early administration of surfactant followed by brief ventilation and extubation to CPAP) reduces need for mechanical ventilation 1

Pitfalls and Caveats

• The timeline of RDS progression is approximate, and characteristic features in each phase often overlap 1
• Severity and resolution of the insult affect the progression timeline 1
• Pulmonary hypertension in early phases is multifactorial (vasoconstriction from alveolar hypoxia, vasoactive mediators, intravascular obstruction) 1
• Poor outcome (death or Type 2 bronchopulmonary dysplasia) can be predicted with reasonable accuracy by day 3 of age using gestational age and ventilatory parameters 3
• Avoid frequent redosing of surfactant (less than every 12 hours) unless surfactant is being inactivated by infection, meconium, or blood 1