What is Neonatal Respiratory Distress Syndrome (NRDS), its pathophysiology, causes, and treatment?

Neonatal Respiratory Distress Syndrome (NRDS): Comprehensive Overview

Definition and Core Pathophysiology

NRDS is a respiratory disorder of preterm newborns caused by surfactant deficiency, leading to alveolar collapse, impaired gas exchange, and progressive respiratory failure. 1

The pathophysiologic cascade unfolds as follows:

• Surfactant deficiency is the primary defect, occurring because preterm lungs lack adequate type II pneumocytes to produce sufficient surfactant 1, 2
• Alveolar collapse occurs at end-expiration due to high surface tension without surfactant, preventing establishment of functional residual capacity 3
• High alveolar-capillary permeability allows serum proteins to leak into airways, which further inhibits any residual surfactant function 1
• Ventilation-perfusion mismatch develops as atelectatic areas remain perfused but unventilated, causing hypoxemia 3
• Increased work of breathing results from decreased pulmonary compliance and the infant's attempts to maintain adequate ventilation 4
• Progressive inflammation occurs from barotrauma, oxygen toxicity, and the underlying lung injury, setting the stage for chronic lung disease 5, 4

Primary Risk Factors and Epidemiology

Prematurity is the dominant risk factor, with highest incidence in infants born at less than 30 weeks gestation and weighing less than 1,000 g. 1

Key risk factors include:

• Gestational age < 30 weeks with exponentially increasing risk at earlier gestations 1
• Birth weight < 1,000 g representing the most vulnerable population 1
• Absence of antenatal corticosteroid administration, which is the most preventable risk factor 1
• Multiple gestation pregnancies due to higher rates of prematurity 1
• Maternal diabetes, cesarean delivery without labor, and perinatal asphyxia 6, 7

Treatment Algorithm

Initial Respiratory Support Strategy

Start with CPAP (5-6 cm H₂O) immediately after birth for all spontaneously breathing preterm infants with respiratory distress, rather than routine intubation. 8, 9

The evidence strongly supports this approach:

• Early CPAP with selective surfactant reduces bronchopulmonary dysplasia and death compared to prophylactic surfactant (RR 0.53,95% CI 0.34-0.83) 8
• CPAP prevents atelectasis by maintaining functional residual capacity and preventing alveolar collapse 5
• CPAP is less invasive than intubation and reduces the combined risk of death or bronchopulmonary dysplasia compared to immediate intubation 5

Surfactant Replacement Therapy

Administer surfactant selectively to infants who show worsening respiratory distress despite CPAP, or immediately to preterm infants born at <30 weeks' gestation requiring mechanical ventilation. 8, 9

Critical details for surfactant administration:

• Animal-derived surfactants are superior to first-generation synthetic surfactants, showing lower mortality (RR 0.86; 95% CI 0.76-0.98) and fewer pneumothoraces (RR 0.63; 95% CI 0.53-0.75) 8
• Early rescue surfactant (within 1-2 hours) is superior to delayed treatment, significantly decreasing mortality (RR 0.84; 95% CI 0.74-0.95), air leak (RR 0.61; 95% CI 0.48-0.78), and chronic lung disease (RR 0.69; 95% CI 0.55-0.86) 8, 9
• INSURE strategy (Intubation, Surfactant, Extubation to CPAP) significantly reduces need for mechanical ventilation (RR 0.67; 95% CI 0.57-0.79) 8

Mechanical Ventilation Support

Use PEEP during positive pressure ventilation for premature newborns to prevent lung collapse at end-expiration. 5

Ventilation principles:

• PEEP maintains lung volume and improves oxygenation by preventing alveolar collapse 5
• Expeditious ventilator adjustments are necessary after surfactant administration to minimize lung injury and air leak 8
• Gentle ventilation strategies minimize barotrauma and oxygen toxicity that contribute to bronchopulmonary dysplasia 5, 4

Monitoring During Surfactant Administration

Anticipate transient airway obstruction, oxygen desaturation, and bradycardia during surfactant administration, requiring immediate ventilator adjustments. 8

Key monitoring points:

• Alterations in cerebral blood flow can occur during administration 8
• Redosing should not occur more frequently than every 12 hours unless surfactant is being inactivated by infection, meconium, or blood 8

Prevention Strategies

Antenatal corticosteroids are the most effective preventive intervention, working synergistically with postnatal surfactant to reduce mortality, RDS severity, and air leaks. 1, 8, 9

The synergistic effect is critical:

• Antenatal steroids and postnatal surfactant work independently and additively, reducing mortality and morbidity more than either intervention alone 8, 9
• Administration between 24-34 weeks gestation when preterm delivery risk is high provides maximum benefit 6

Long-term Outcomes and Complications

RDS is the primary precursor to bronchopulmonary dysplasia (BPD), with persistent airway obstruction and hyperreactivity extending into childhood. 1

Long-term sequelae include:

• Average FEV₁ approximately 80% of controls at 6-15 years of age in survivors 1
• Chronic lung disease of infancy represents the final common pathway, characterized by alveolar simplification in the modern era rather than the fibrosis seen historically 5
• Multisystem complications beyond the respiratory system are common in these infants 5

Critical Pitfalls to Avoid

• Do not routinely intubate with prophylactic surfactant as the first-line approach, as this increases complications compared to CPAP-first strategy 8
• Do not delay surfactant beyond 2 hours in infants requiring mechanical ventilation, as early rescue is superior 8, 9
• Do not use surfactant for congenital diaphragmatic hernia, as it has not shown improved outcomes 8
• Ensure specialized expertise is available, as surfactant administration requires clinicians experienced in intubation and ventilator management 8

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