What is the prescription for surfactant replacement therapy in preterm infants with Respiratory Distress Syndrome (RDS)?

Surfactant Prescription for Respiratory Distress Syndrome

For preterm infants <30 weeks' gestation with severe RDS requiring mechanical ventilation, administer surfactant immediately after initial stabilization, with an initial dose of 2.5 mL/kg (poractant alfa) or 4 mL/kg (beractant) given intratracheally. 1, 2, 3

Initial Respiratory Support Strategy

The approach to surfactant therapy has evolved significantly, with current evidence favoring selective rather than routine prophylactic administration:

• Start with CPAP (5-6 cm H₂O) immediately after birth for spontaneously breathing preterm infants with respiratory distress, rather than routine intubation 1, 4
• Early CPAP with selective surfactant administration results in lower rates of bronchopulmonary dysplasia and death compared to prophylactic surfactant therapy (RR 0.53,95% CI 0.34-0.83) 1, 5, 4
• Administer surfactant selectively only when infants demonstrate worsening respiratory distress despite CPAP support 1

This represents a shift from older 2008 guidelines that recommended prophylactic surfactant for extremely preterm infants 1. The more recent 2014 American Academy of Pediatrics guidelines provide stronger evidence (Level 1) supporting the CPAP-first approach 1.

Specific Dosing Regimens

Poractant Alfa (Curosurf)

• Initial dose: 2.5 mL/kg birth weight (200 mg/kg phospholipids) administered intratracheally 2
• Repeat doses: Up to two additional doses of 1.25 mL/kg may be given at approximately 12-hour intervals 2
• Maximum total dose: 5 mL/kg (initial plus repeat doses) 2
• Administration method: Either as two divided aliquots through a 5 French end-hole catheter, or as a single bolus through the secondary lumen of a dual lumen endotracheal tube 2

Beractant (Survanta)

• Initial dose: 4 mL/kg birth weight (100 mg/kg phospholipids) administered intratracheally 3
• Repeat doses: Up to four doses total can be administered in the first 48 hours, given no more frequently than every 6 hours 3
• Administration method: Four quarter-dose aliquots through a 5 French end-hole catheter, with the infant repositioned between each aliquot (head down/right, head down/left, head up/right, head up/left) 3

Poractant alfa at the higher initial dose (200 mg/kg) demonstrates superior outcomes compared to beractant, including decreased mortality, less need for additional doses, and faster weaning of oxygen in infants <32 weeks' gestation 6, 7. Animal-derived surfactants containing surfactant proteins B and C are more effective than 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) 5, 6.

Timing of Administration

Early rescue surfactant (<2 hours of age) is superior to delayed treatment:

• Significantly decreases mortality (RR 0.84; 95% CI 0.74-0.95) 1, 5
• Reduces air leak syndromes (RR 0.61; 95% CI 0.48-0.78) 1, 5
• Decreases chronic lung disease (RR 0.69; 95% CI 0.55-0.86) 1, 5

For prevention strategy in high-risk infants, the first dose should be given as soon as possible, preferably within 15 minutes of birth 3. However, the current preferred approach is CPAP-first with selective surfactant rather than prophylactic administration 1.

INSURE Technique (Intubation-Surfactant-Extubation)

The INSURE strategy significantly reduces the need for mechanical ventilation (RR 0.67; 95% CI 0.57-0.79) and oxygen requirement at 28 days 5, 4:

1. Intubate the infant and confirm proper endotracheal tube placement 2, 3
2. Administer surfactant via the endotracheal tube 2, 3
3. Extubate to CPAP as soon as clinically feasible, ideally within one hour 8, 5

This approach reduces mechanical ventilation exposure (RR 0.51,95% CI 0.32-0.76) compared to continued mechanical ventilation after surfactant administration 8.

Preparation and Administration

Preparation

• Warm surfactant to room temperature for at least 20 minutes or in hand for at least 8 minutes before administration 3
• Do not use artificial warming methods 3
• Gently swirl (do not shake) if settling occurs 3
• Do not filter the surfactant 3
• Each vial should be entered only once; discard unused portions 3

Administration Technique

• Confirm endotracheal tube placement and patency before administration 2, 3
• Allow infant to stabilize before proceeding with dosing 3
• Administer through a 5 French end-hole catheter inserted through the endotracheal tube 2, 3
• The catheter tip should protrude just beyond the endotracheal tube above the infant's carina, not into a mainstem bronchus 3

Monitoring During Administration

Transient adverse effects are common and require immediate intervention:

• Bradycardia, hypotension, oxygen desaturation, and endotracheal tube blockage may occur during administration 2
• Stop surfactant administration if these events occur and take appropriate measures to stabilize the infant 2
• Manually ventilate for at least 30 seconds or until clinically stable after each aliquot 3
• Frequently assess and modify oxygen and ventilatory support in response to rapid improvements in lung compliance 2

Repeat Dosing Criteria

Administer repeat doses based on evidence of continuing respiratory distress:

• Redosing should not be needed more frequently than every 12 hours unless surfactant is being inactivated by infection, meconium, or blood 5
• For beractant, doses may be given every 6 hours if needed, up to four total doses in 48 hours 3
• For poractant alfa, up to two repeat doses of 1.25 mL/kg may be given at 12-hour intervals 2
• Radiographic confirmation of RDS should be obtained before administering additional doses to infants who received a prevention dose 3

Secondary Surfactant Deficiency (Off-Label Use)

Rescue surfactant may be considered for term and late-preterm infants with hypoxic respiratory failure from:

• Meconium aspiration syndrome: Improves oxygenation and reduces need for ECMO without increased morbidity 1, 5
• Sepsis/pneumonia: May benefit from surfactant therapy 1, 5
• Pulmonary hemorrhage: May reduce morbidity and mortality 1, 5

Do not use surfactant for congenital diaphragmatic hernia, as it has not shown improved outcomes 1, 5.

Synergy with Antenatal Steroids

Antenatal steroids and postnatal surfactant work independently and additively:

• Both interventions together reduce mortality, severity of RDS, and air leaks more than either alone 1, 5
• Administer surfactant regardless of antenatal steroid exposure if the infant meets criteria for treatment 1

Critical Pitfalls to Avoid

• Do not delay CPAP initiation in spontaneously breathing preterm infants 4
• Do not routinely intubate for prophylactic surfactant without first attempting CPAP 1, 4
• Do not administer surfactant into a mainstem bronchus; ensure catheter tip is above the carina 3
• Do not use excessive ventilation pressures after surfactant administration, as lung compliance improves rapidly 2
• Do not warm surfactant using artificial heating methods 3
• Do not shake the vial; gently swirl only 3
• Do not return warmed surfactant to refrigerator more than once 3

Personnel Requirements

Surfactant administration requires specialized expertise:

• Must be administered by or under supervision of clinicians experienced in intubation, ventilator management, and general care of premature infants 3
• Pediatric providers without expertise should wait for the transport team to arrive rather than attempting administration 1
• One person should administer the dose while another positions and monitors the infant 3