Saidala 24: Lung surfactants

1. Introduction

Lung surfactants are a specialized pharmacological class of agents used to replace or supplement deficient or dysfunctional pulmonary surfactant in neonates and, in some cases, adults. Pulmonary surfactant is an essential lipoprotein complex secreted by type II alveolar epithelial cells that reduces surface tension in the alveoli, preventing collapse during expiration and promoting efficient gas exchange.

Clinical use of exogenous lung surfactants is primarily focused on the management of neonatal respiratory distress syndrome (NRDS), which occurs in preterm infants due to immature lungs and insufficient surfactant production. However, expanding indications include acute respiratory distress syndrome (ARDS) in adults, meconium aspiration syndrome, pulmonary hemorrhage, and congenital diaphragmatic hernia.

The development and refinement of surfactant therapies represent one of the most significant advances in neonatal medicine and have dramatically improved the survival and outcomes of premature infants.

2. Physiological Role of Endogenous Surfactant

Pulmonary surfactant is a mixture primarily composed of:

Phospholipids (90%, mainly dipalmitoylphosphatidylcholine (DPPC))
Proteins (10%, including surfactant proteins SP-A, SP-B, SP-C, and SP-D)

Its key functions include:

Lowering alveolar surface tension, preventing alveolar collapse (atelectasis)
Stabilizing alveoli of various sizes
Enhancing lung compliance
Modulating immune responses via surfactant proteins

In preterm infants (<32 weeks gestation), surfactant synthesis and secretion are often insufficient, predisposing them to NRDS.

3. Indications for Exogenous Surfactant Therapy

Neonatal Respiratory Distress Syndrome (NRDS)
Meconium Aspiration Syndrome
Pulmonary Hemorrhage
Congenital Diaphragmatic Hernia (off-label)
ARDS in children and adults (investigational/off-label)
Bronchopulmonary Dysplasia prevention (under research)

4. Classification of Lung Surfactants

Lung surfactants are broadly classified into:

A. Natural (Animal-Derived) Surfactants

Obtained from bovine or porcine lungs via lavage or mincing. They contain phospholipids and essential hydrophobic proteins (mainly SP-B and SP-C), which are important for surface tension reduction.

Examples:

Beractant (Survanta) – modified bovine lung extract
Poractant alfa (Curosurf) – porcine lung extract
Calfactant (Infasurf) – calf lung lavage extract
Bovactant (Alveofact) – bovine lung extract

B. Synthetic Surfactants

Produced chemically or by recombinant techniques. Earlier synthetic versions lacked surfactant proteins, reducing efficacy. Newer generations include protein analogs or recombinant proteins.

Examples:

Lucinactant (Surfaxin) – synthetic DPPC-based with KL4 peptide (SP-B analog)
Colfosceril palmitate (Exosurf) – older generation, no longer widely used

5. Mechanism of Action

Lung surfactants act by reducing alveolar surface tension through the following mechanisms:

Spreading a monolayer of phospholipids across the alveolar surface
Increasing pulmonary compliance, allowing easier lung inflation
Preventing alveolar collapse during expiration (minimizing atelectasis)
Redistributing ventilation to previously collapsed alveoli
Enhancing oxygenation and CO₂ elimination

Surfactant proteins (especially SP-B and SP-C) promote phospholipid spreading and adsorption, which enhances the physical stability and performance of the surfactant.

6. Formulation and Composition Overview

Product	Source	SP Content	Main Phospholipids	Protein Additives	Approx. Dose
Survanta	Bovine	SP-B, SP-C	DPPC, PG, PA	None	100 mg/kg
Curosurf	Porcine	SP-B, SP-C	DPPC, PG	None	100–200 mg/kg
Infasurf	Calf lavage	SP-B, SP-C	DPPC, PG, PI	None	3 mL/kg
Surfaxin	Synthetic	SP-B analog	DPPC, PG	KL4 peptide	5.8 mL/kg
Exosurf	Synthetic	None	DPPC, hexadecanol	Tyloxapol	5 mL/kg (obsolete)

Abbreviations: DPPC = dipalmitoylphosphatidylcholine, PG = phosphatidylglycerol, PA = palmitic acid, PI = phosphatidylinositol

7. Administration

Route:

Intratracheal instillation via an endotracheal tube (ETT)
Must be administered in an intubated, mechanically ventilated infant
Timing can be prophylactic (within 15–30 minutes after birth) or rescue (after clinical diagnosis of RDS)

Technique:

Bolus instillation or divided doses
Patient may be turned between doses to promote even distribution
INSURE technique (Intubate-SURfactant-Extubate) used for minimally invasive support
Less invasive surfactant administration (LISA) techniques are evolving

8. Dosage Protocols (Neonatal)

Drug	Initial Dose	Repeat Doses	Max Number of Doses
Survanta	100 mg/kg (4 mL/kg)	Every 6 hours	Up to 4 doses
Curosurf	100–200 mg/kg	100 mg/kg at 12 hrs	Up to 3 doses
Infasurf	3 mL/kg	Every 12 hours	Up to 3 doses
Surfaxin	5.8 mL/kg	Every 6 hours	Up to 4 doses

9. Clinical Efficacy and Benefits

Improved oxygenation (increased PaO₂, reduced FiO₂ requirement)
Reduced risk of pneumothorax
Decreased need for mechanical ventilation
Lower mortality in preterm infants with NRDS
Fewer cases of bronchopulmonary dysplasia when used early

Meta-analyses and Cochrane Reviews confirm that natural surfactants are more effective than older synthetic versions, especially regarding mortality reduction and air leak syndromes.

10. Adverse Effects

Reaction	Description
Transient bradycardia	Often due to vagal stimulation during instillation
Hypoxia	Due to airway obstruction or reduced lung compliance
Pulmonary hemorrhage	Risk increases with surfactant use, especially in ELBW infants
Airway obstruction	Improper administration can lead to plugging
Infection risk	Not directly caused by surfactants but due to intubation

Management:

Slow and careful administration
Pre-oxygenation
Suctioning of airways post-dose
Close cardiorespiratory monitoring

11. Contraindications

Lung surfactants are not typically contraindicated, but caution is advised in:

Infants with major pulmonary malformations or congenital heart disease
Airway anomalies that impair administration
Hypersensitivity to any components (rare, especially with synthetic agents)

12. Drug Interactions

Lung surfactants are topical pulmonary agents and are not systemically absorbed, so drug–drug interactions are negligible. However, factors to monitor:

Concurrent respiratory medications (e.g., bronchodilators, steroids) may affect lung compliance
Ventilator settings must be adjusted post-surfactant to avoid barotrauma

13. Adult and Pediatric Use (Beyond Neonates)

Though off-label, there is increasing interest in surfactant therapy in:

ARDS (Acute Respiratory Distress Syndrome)

Clinical trials in adults and children with ARDS have yielded mixed results
Surfactant deficiency due to protein leakage, inflammation, and inactivation
Some benefit in direct lung injuries (e.g., aspiration), but routine use is not yet established

Meconium Aspiration Syndrome

Meconium inactivates endogenous surfactant
Surfactant lavage or bolus therapy improves oxygenation and reduces ECMO need

COVID-19 and Viral Pneumonias

Surfactant dysfunction plays a role in severe COVID-19 pneumonia
Trials underway for aerosolized surfactants in adults

14. Emerging Approaches and Research

Aerosolized surfactants (e.g., nebulized forms) to enable non-invasive delivery
Recombinant surfactant proteins (e.g., SP-C analogs) for improved efficacy
LISA and MIST techniques (Minimally Invasive Surfactant Therapy) to reduce intubation needs
Gene therapy for surfactant protein deficiencies (under investigation)
Ex-vivo surfactant replacement in artificial lung support systems

15. Marketed Lung Surfactants (Global Overview)

Brand Name	Generic/Source	Manufacturer	Region
Survanta	Beractant (bovine)	AbbVie	USA, global
Curosurf	Poractant alfa (porcine)	Chiesi Farmaceutici	EU, USA
Infasurf	Calfactant (bovine)	ONY Biotech	USA
Alveofact	Bovactant (bovine)	Lyomark Pharma	Europe
Surfaxin	Lucinactant (synthetic)	Discovery Labs (discontinued)	USA (legacy)

16. Regulatory Status

Product	FDA Approved	EMA Approved	Neonatal Use	Adult Use (ARDS)
Survanta	Yes	Yes	Yes	No (off-label)
Curosurf	Yes	Yes	Yes	Under trial
Infasurf	Yes	N/A	Yes	No
Surfaxin	Yes (withdrawn)	N/A	Yes	No

17. Summary of Clinical Guidelines

According to guidelines from the American Academy of Pediatrics (AAP) and European Consensus Guidelines:

Surfactant therapy is recommended for all infants <30 weeks gestation with signs of NRDS
Early rescue (<2 hours) is preferred over prophylactic use unless intubated at birth
Use the least invasive method of delivery feasible
Repeat dosing is acceptable if ongoing oxygen need or radiographic evidence of RDS persists

Saidala 24

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Wednesday, August 6, 2025

Lung surfactants