Surfactant Replacement Therapy for RDS in Neonates: Indian NICU Protocol

Introduction to Surfactant Replacement Therapy

Respiratory distress syndrome (RDS), caused by deficiency of pulmonary surfactant in premature lungs, remains the leading cause of respiratory morbidity and mortality in preterm neonates worldwide. In India, where preterm births account for approximately 13 percent of all deliveries, RDS is responsible for a significant proportion of NICU admissions and neonatal deaths. Surfactant replacement therapy, introduced into clinical practice in the late 1980s, has been one of the most transformative advances in neonatal medicine, reducing mortality from RDS by approximately 30 to 40 percent.

The NNF guidelines for management of RDS in Indian NICUs incorporate international best practices while addressing practical challenges including cost, availability, and varying levels of NICU infrastructure across the country. This article provides a comprehensive overview of surfactant pharmacology, available preparations in India, dosing protocols, administration techniques, and evidence-based management strategies.

Physiology of Pulmonary Surfactant

Pulmonary surfactant is a complex mixture of phospholipids (approximately 80 percent), surfactant proteins (approximately 10 percent), and neutral lipids (approximately 10 percent) produced by type II alveolar pneumocytes beginning around 24 weeks of gestation. The critical component is dipalmitoylphosphatidylcholine (DPPC), which reduces surface tension at the air-liquid interface of alveoli, preventing atelectasis during expiration.

Surfactant Proteins

• SP-A: Hydrophilic protein involved in innate immunity and surfactant homeostasis. Not present in commercial surfactant preparations.
• SP-B: Essential hydrophobic protein critical for surfactant function. Genetic deficiency of SP-B is lethal. Present in natural surfactant preparations.
• SP-C: Hydrophobic protein that enhances surface film stability. Present in natural surfactant preparations.
• SP-D: Hydrophilic protein involved in host defense. Not present in commercial preparations.

Surfactant production increases significantly after 34 to 36 weeks of gestation, which is why RDS predominantly affects infants born before this gestational age. Antenatal corticosteroids (betamethasone or dexamethasone) accelerate surfactant production and are a key complementary intervention to postnatal surfactant therapy.

Surfactant Preparations Available in India

Preparation	Type	Source	Dose	Volume	Approximate Cost (INR)
Poractant alfa (Curosurf)	Natural	Porcine lung	200 mg/kg initial, 100 mg/kg repeat	2.5 mL/kg initial	15,000-25,000
Beractant (Survanta)	Natural	Bovine lung	100 mg/kg per dose	4 mL/kg	8,000-15,000
Calfactant (Infasurf)	Natural	Calf lung	105 mg/kg per dose	3 mL/kg	10,000-18,000
Bovine surfactant (Cadisurf)	Natural	Bovine lung	100 mg/kg per dose	4 mL/kg	4,000-8,000

Poractant alfa at a dose of 200 mg/kg has been shown in randomized controlled trials to be superior to both beractant 100 mg/kg and poractant alfa 100 mg/kg in reducing mortality and the need for repeat dosing. However, the significantly higher cost of imported surfactant preparations is a major consideration in the Indian healthcare setting. Indian-manufactured bovine surfactant preparations have improved access considerably, particularly in government hospital NICUs.

Indications for Surfactant Therapy

Early Rescue Therapy (Preferred Approach)

Current NNF and European Consensus guidelines recommend early rescue surfactant administration within the first 2 hours of life for preterm neonates who develop signs of RDS despite initial CPAP support. The FiO2 threshold for surfactant administration on CPAP has been defined as 0.30 for infants below 26 weeks gestation and 0.40 for infants above 26 weeks gestation.

Criteria for Surfactant Administration

1. Clinical evidence of respiratory distress: tachypnea, grunting, retractions, cyanosis
2. Chest X-ray consistent with RDS (ground-glass appearance, air bronchograms, low lung volumes)
3. FiO2 requirement above threshold on adequate CPAP (5-8 cm H2O)
4. Gestational age typically below 34 weeks, though term neonates with RDS may also benefit

Prophylactic vs Rescue Approach

Earlier guidelines recommended prophylactic surfactant administration to all infants below 26 to 28 weeks gestation. However, current evidence from trials using early CPAP (including the SUPPORT and COIN trials) demonstrates that early CPAP with selective rescue surfactant is equivalent or superior to routine prophylaxis, provided that surfactant can be administered rapidly when needed. This approach is particularly relevant in Indian NICUs where CPAP availability has expanded significantly through devices and programs supported by organizations like HEAMAC.

Administration Techniques

INSURE Technique

The INSURE (INtubate, SURfactant, Extubate) technique is the most widely practiced method in Indian NICUs. The procedure involves brief intubation under direct laryngoscopy, surfactant instillation through the endotracheal tube, brief positive pressure ventilation, and rapid extubation to CPAP within minutes. This technique minimizes the duration of mechanical ventilation and is associated with reduced rates of BPD compared with continued mechanical ventilation after surfactant.

LISA/MIST Technique

Less Invasive Surfactant Administration (LISA), also known as Minimally Invasive Surfactant Therapy (MIST), involves inserting a thin catheter (5F feeding tube or specially designed LISA catheter) through the vocal cords under direct laryngoscopy while the infant remains on CPAP and breathing spontaneously. Surfactant is instilled slowly over 1 to 5 minutes. This technique avoids intubation and positive pressure ventilation entirely. European guidelines now recommend LISA as the preferred method of surfactant administration. In India, adoption is growing in tertiary NICUs, though the technique requires training and experience.

Standard Intubation and Administration

In centres where INSURE or LISA expertise is not available, surfactant is administered through the endotracheal tube after standard intubation. The surfactant is given in aliquots with the infant positioned in different positions (left lateral, right lateral, supine) to ensure even distribution. This method is more common in Level II NICUs and resource-limited settings in India.

Dosing Protocol

Initial Dose

For poractant alfa, the recommended initial dose is 200 mg/kg (2.5 mL/kg of the 80 mg/mL preparation). For beractant and Indian bovine surfactant preparations, the initial dose is 100 mg/kg (4 mL/kg of the 25 mg/mL preparation). The surfactant should be warmed to room temperature before administration. Do not shake the vial; gentle swirling is acceptable.

Repeat Dosing

A second dose of surfactant may be administered 6 to 12 hours after the first dose if the infant continues to require FiO2 above 0.30 on adequate ventilatory support. A maximum of three doses is generally recommended. Poractant alfa repeat doses are given at 100 mg/kg (1.25 mL/kg). The NNF protocol recommends reassessing the infant 6 hours after the initial dose before deciding on repeat administration.

Post-Administration Monitoring

• Immediate (first 30 minutes): Continuous SpO2, heart rate, and blood pressure monitoring. Rapid improvement in oxygenation is expected; FiO2 should be weaned promptly to avoid hyperoxia.
• Ventilator parameters: Peak inspiratory pressure and FiO2 often decrease rapidly. Ventilator settings must be adjusted proactively to prevent pneumothorax from over-distension.
• Chest X-ray: Post-surfactant X-ray at 6 hours to assess lung expansion and exclude complications.
• Blood gas: Arterial or capillary blood gas within 1 to 2 hours to guide ventilator management.
• Endotracheal tube position: Verify ETT position before surfactant administration to ensure bilateral distribution.

Complications and Adverse Effects

Immediate Complications

• Transient desaturation and bradycardia during administration
• Endotracheal tube obstruction by surfactant
• Pulmonary hemorrhage (more common with rapid improvement in compliance)
• Unilateral surfactant distribution with right upper lobe preference

Potential Adverse Effects

Surfactant therapy is generally very safe. Rarely, transient hemodynamic changes including hypotension and increased cerebral blood flow have been reported. The risk of pulmonary hemorrhage is approximately 5 to 10 percent and is more common in extremely preterm infants with a hemodynamically significant PDA.

Cost Considerations in Indian NICUs

Surfactant cost remains a significant barrier to optimal RDS management in India. A single dose of imported surfactant may cost INR 15,000 to 25,000, which represents a substantial financial burden for families, particularly in government hospitals where out-of-pocket expenses are common. Indian-manufactured bovine surfactant preparations have helped address this cost barrier, with per-dose costs of INR 4,000 to 8,000. Several state government health schemes, including the Rashtriya Bal Swasthya Karyakram (RBSK), now cover surfactant costs for eligible neonates.

NNF Recommendations Summary

1. Administer antenatal corticosteroids to all women at risk of preterm delivery between 24 and 34 weeks gestation.
2. Initiate CPAP early in the delivery room for all preterm infants with respiratory distress.
3. Administer surfactant as early rescue therapy within 2 hours if FiO2 exceeds threshold on CPAP.
4. Use natural surfactant preparations; poractant alfa 200 mg/kg is the preferred initial dose where available.
5. Use INSURE or LISA technique where expertise exists to minimize mechanical ventilation duration.
6. Consider repeat dosing at 6 to 12 hours if clinical criteria are met, up to a maximum of three doses.

Conclusion

Surfactant replacement therapy is an essential intervention for neonatal RDS that has dramatically improved survival in preterm infants. In the Indian context, expanding access to affordable surfactant preparations, training healthcare providers in INSURE and LISA techniques, and ensuring complementary CPAP infrastructure are critical priorities for improving neonatal outcomes. Evidence-based protocols guided by NNF recommendations should be implemented across all NICUs managing preterm neonates with RDS.