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

Neonatal Respiratory Distress Syndrome: Pathophysiology and Treatment

Definition and Pathophysiology

Neonatal Respiratory Distress Syndrome (NRDS) is a respiratory failure condition in preterm infants caused by surfactant deficiency due to immature lung development, leading to alveolar collapse, decreased pulmonary compliance, and impaired gas exchange. 1, 2

The disease process involves:

• Inadequate surfactant production by immature type II pneumocytes, preventing alveoli from remaining open during expiration 1, 2
• Formation of hyaline membranes that block small airways, creating ventilation-perfusion mismatch 2
• Progressive atelectasis and over-distension of airways, contributing to inflammation that can progress to bronchopulmonary dysplasia 2
• Inflammatory cascade that may begin in utero with chorioamnionitis exposure, causing surfactant inactivation through protein leak into airways 3

Clinical presentation includes cyanosis, grunting, intercostal retractions, tachypnea, and progressive hypoxia if untreated 4.

Treatment Algorithm

Initial Respiratory Support

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

• Early CPAP maintains functional residual capacity and prevents alveolar collapse 5
• This approach significantly reduces bronchopulmonary dysplasia and death compared to prophylactic surfactant (RR 0.53,95% CI 0.34-0.83) 5
• Routine prophylactic intubation with surfactant is no longer recommended as first-line therapy due to increased complication risk 5

Surfactant Administration Strategy

Administer surfactant selectively to infants showing worsening respiratory distress despite CPAP support, using early rescue timing (within 1-2 hours of birth). 5, 6

Specific Indications:

• Preterm infants <30 weeks' gestation requiring mechanical ventilation for severe RDS after initial stabilization 5
• Infants on CPAP with escalating oxygen requirements or work of breathing 5

Timing Evidence:

• Early rescue surfactant (<2 hours) is superior to delayed treatment (≥2 hours), 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) 5
• Prophylactic surfactant (within 10-30 minutes) may benefit extremely preterm infants without antenatal steroid exposure 6

Surfactant Selection and Administration

Use animal-derived surfactants rather than first-generation synthetic preparations. 5

• Animal-derived surfactants demonstrate lower mortality rates (RR 0.86; 95% CI 0.76-0.98) and fewer pneumothoraces (RR 0.63; 95% CI 0.53-0.75) compared to synthetic alternatives 5
• Newer synthetic surfactants with surfactant protein-like activity show promise but require further validation 6

Administration Technique:

• Deliver through endotracheal tube as bolus, smaller aliquots, or infusion (no significant outcome differences between methods) 5
• Use the INSURE strategy (Intubation, Surfactant administration, Extubation to CPAP) to significantly reduce mechanical ventilation need (RR 0.67; 95% CI 0.57-0.79) and oxygen requirement at 28 days 5
• Requires specialized expertise; must be performed by clinicians experienced in intubation and ventilator management 5

Post-Surfactant Management

Make expeditious ventilator setting changes after surfactant administration to minimize lung injury and air leak. 5

Monitoring Requirements:

• Watch for transient airway obstruction, oxygen desaturation, bradycardia, and cerebral blood flow alterations 5
• Adjust ventilator settings immediately as lung compliance improves 5
• Redosing should not occur more frequently than every 12 hours unless surfactant inactivation from infection, meconium, or blood is suspected 5

Synergistic Therapies

Antenatal steroids and postnatal surfactant work independently and additively, reducing mortality, RDS severity, and air leaks more effectively than either alone 5, 6

• This combination represents the most powerful intervention for preventing and treating RDS 6
• Antenatal steroids may reduce surfactant need in infants born after 27-28 weeks' gestation 6

Treatment for Secondary Surfactant Deficiency

Surfactant therapy may benefit late-preterm and term neonates with secondary surfactant deficiency from meconium aspiration syndrome, pneumonia/sepsis, and pulmonary hemorrhage. 5

Contraindication:

• Do not use surfactant for congenital diaphragmatic hernia, as it has not shown improved outcomes 5

Common Pitfalls and Caveats

Avoid over-treating stable infants on CPAP who do not meet criteria for surfactant administration, as unnecessary intubation increases complications 5

Do not delay surfactant in infants meeting criteria, as timing significantly impacts outcomes with early administration superior to delayed treatment 5, 6

Recognize that some very immature infants have poor surfactant response or early relapse due to severe inflammatory injury and surfactant inactivation; these cases may require higher or repetitive doses of natural surfactant 3

Understand that RDS has multifactorial pathogenesis involving intrauterine inflammatory exposure ("first hit") followed by postnatal insults (oxygen toxicity, mechanical ventilation) that perpetuate lung injury 3