What is the role of surfactant in preterm infants with Respiratory Distress Syndrome (RDS)?

Role of Surfactant in Preterm Infants with Respiratory Distress Syndrome (RDS)

Surfactant replacement therapy significantly reduces mortality, air leaks, and severity of respiratory distress syndrome in preterm infants with surfactant deficiency, and should be administered as soon as possible after intubation regardless of antenatal steroid exposure or gestational age. 1

Mechanism and Benefits

• Endogenous pulmonary surfactant reduces surface tension at the air-liquid interface of alveoli during ventilation and stabilizes alveoli against collapse at resting transpulmonary pressures 2
• Surfactant deficiency in preterm infants results in RDS characterized by poor lung expansion, inadequate gas exchange, and gradual collapse of the lungs (atelectasis) 2
• Exogenous surfactant compensates for this deficiency and restores surface activity to the lungs 2
• Surfactant replacement therapy has been proven to reduce:
  • Mortality (RR: 0.63,95% CI: 0.47 to 0.84) 1
  • Pneumothorax (RR: 0.62,95% CI: 0.42 to 0.89) 1
  • Pulmonary interstitial emphysema (RR: 0.54,95% CI: 0.36 to 0.82) 1
  • Combined outcome of bronchopulmonary dysplasia and death (RR: 0.85,95% CI: 0.76 to 0.95) 1

Prophylactic vs. Rescue Surfactant

• Prophylactic surfactant (administered before onset of respiratory symptoms, within 10-30 minutes after birth) is beneficial for extremely preterm infants at high risk of RDS, especially those without antenatal steroid exposure 1
• Early rescue surfactant (within 1-2 hours of birth) is superior to late rescue surfactant (≥2 hours after birth) in reducing adverse respiratory outcomes in infants <30 weeks' gestation 1
• In infants <30 weeks' gestation, prophylactic surfactant compared to rescue surfactant reduces:
  • Death (NNT: 22) 1
  • Pneumothorax (NNT: 47) 1
  • Pulmonary interstitial emphysema (NNT: 40) 1

Types of Surfactant

• Both animal-derived (natural) and synthetic surfactants decrease respiratory morbidity and mortality in preterm infants with surfactant deficiency 1
• Natural surfactants are currently preferred over protein-free synthetic surfactants 3
• Newer synthetic surfactants with surfactant protein-like activity show promise as treatments for surfactant deficiency disorders 1

Surfactant Administration Techniques

• Traditional administration involves intubation and mechanical ventilation 4
• Recent evidence supports less invasive approaches:
  • INSURE technique (Intubation, Surfactant administration, and Extubation to CPAP) 1, 4
  • Surfactant administration via thin catheter in spontaneously breathing infants has shown reduced risk of death or BPD compared to administration via endotracheal tube (RR 0.59,95% CI 0.48 to 0.73) 4
• Multiple surfactant doses may be required for optimal outcomes in some infants 2

Impact on Complications of Prematurity

• Surfactant therapy reduces the combined outcome of death or bronchopulmonary dysplasia compared to no surfactant replacement 1
• The incidence of BPD is lower in treated infants born at ≥30 weeks' gestation compared with untreated infants of the same gestational age 1
• Surfactant therapy has not been shown to affect the incidence of neurologic, developmental, behavioral, medical, or educational outcomes in preterm infants 1
• The incidence of other complications such as intraventricular hemorrhage, necrotizing enterocolitis, nosocomial infections, retinopathy of prematurity, and patent ductus arteriosus has not changed with surfactant replacement 1

Synergy with Antenatal Steroids

• Antenatal steroids and postnatal surfactant replacement independently and additively reduce mortality, severity of RDS, and air leaks in preterm infants 1
• Antenatal steroids may reduce the need for prophylactic and early rescue surfactant replacement in infants born after 27-28 weeks' gestation 1

Clinical Implications

• FDA has approved surfactant (poractant alfa) for rescue treatment of RDS in premature infants, including reduction of mortality and pneumothoraces 2
• Surfactant should be administered as soon as possible after intubation in infants with RDS, regardless of gestational age or antenatal steroid exposure 1
• Preterm and term neonates receiving surfactant should be managed by personnel with technical and clinical expertise to administer surfactant safely and manage multisystem illness 1

Emerging Approaches

• Continuous positive airway pressure (CPAP) with or without surfactant may reduce the need for additional surfactant and incidence of bronchopulmonary dysplasia 1
• Aerosolized surfactant administration is being investigated as a non-invasive delivery method 3
• Surfactant administration via thin catheter to spontaneously breathing infants on CPAP is showing promising results 4

The evidence clearly demonstrates that surfactant therapy is a cornerstone in the management of RDS in preterm infants, with significant benefits for mortality and respiratory morbidity. The timing, method of administration, and integration with other therapies like antenatal steroids and CPAP continue to evolve to optimize outcomes.