Pulmonary surfactant is a lipoprotein complex responsible for preventing the collapse of alveoli and increasing lung compliance.[1]Therapeutically,  exogenous surfactant administration, or surfactant replacement therapy(SRT), is considered in preterm infants with radiographic (small volume lungs, haziness/ ground-glass appearance, air bronchograms, and loss of cardiac borders on chest radiographs) and clinical evidence of neonatal respiratory distress syndrome (NRDS).[2] Surfactant administration in preterm infants with NRDS reduces morbidity and mortality. There is a reduced risk of air leak and chronic lung disease. In NRDS, the earlier surfactant is used, the better the outcomes.  Also, the outcome is reportedly better, if early surfactant administration is followed by extubation of preterm infants with RDS as compared to prolonged ventilation after surfactant administration.

Therapeutically, surfactant administration is also indicated in infants who have meconium aspiration syndrome. Surfactant use, in this case, will recover oxygenation and reduce the need for extracorporeal membrane oxygenation (ECMO). Also, infants who undergo intubation for any reason, irrespective of their gestational age or infants who have respiratory failure requiring mechanical ventilation, can receive surfactant therapy.

Prophylactic use of surfactant is indicated in the neonates who are predisposed to the development of NRDS. These include those who are born before 32 weeks gestation and those with low birth weights (less than 1300 gm). In premature infants, at risk for developing RDS, the surfactant administration with brief lung-protective ventilation (followed by extubation to nasal CPAP) has been found to lower incidence of mechanical ventilation, air leak syndromes, and result in a lower incidence of pneumothorax, pulmonary interstitial emphysema and improved survival without bronchopulmonary dysplasia. Prophylactic surfactant is also indicated in infants with laboratory evidence of surfactant deficiency (lecithin/sphingomyelin ratio of less than 2 to 1, evidence of lung immaturity on bubble stability test or absence of phosphatidylglycerol). Surfactant replacement therapy may also be a consideration in other situations like worsening pulmonary hemorrhage.[3]

 The use of surfactant may also be beneficial in case of severe respiratory syncytial virus-induced respiratory failure.[3] In this case, there may be an improvement in gas exchange and respiration, contributing to shortened hospital stay and duration of mechanical ventilation.

As mentioned above, pulmonary surfactant is a lipoprotein. Its production begins around 26 weeks gestation and reaches mature levels at approximately 35 weeks. It is produced in the endoplasmic reticulum (ER) of type two pneumocytes and secreted from the lamellar bodies of type two pneumocytes.[4] Other cells in the lung, namely club or Clara cells, also produce surfactant. This lipoprotein mixture enhances lung compliance and aids in lowering the surface tension of the air-liquid interface within alveolar walls, which will ultimately prevent atelectasis.[1]

A large portion of the composition of surfactant is phospholipid dipalmitoylphosphatidylcholine (DPPC), which makes up about 50% of its structure.[4] Phosphatidylglycerol is the second most abundant phospholipid in the structure. Other lipid constituents of surfactant include neutral lipids such as cholesterol and other phospholipids such as sphingomyelin (SM). Surfactant proteins comprise about 10% of the structure and interact extensively with phospholipids. They are SP-A, SP-B, SP-C, and SP-D. The SP-A and SP-D proteins are part of the innate immune response. These proteins coat bacteria and viruses, allowing phagocytosis and destruction by macrophages.[5] SP-A also appears to be a part of a negative feedback mechanism that controls the release of surfactant from type II alveolar cells. SP-B and SP-C are hydrophobic proteins that control the rate at which surfactant covers the surface of alveoli.

The American Academy of Pediatrics 2014 guidelines recommend immediate management of all preterm infants with nasal continuous positive airway pressure. Subsequently, in selected patients, surfactant administration may be considered as an alternative to intubation with prophylactic or early surfactant administration. Surfactant replacement therapy is administered by trained personnel in a clinical setting where equipment for intubation and resuscitation are readily available.

The endotracheal instillation of surfactant is the most widely accepted technique. Surfactant is administered in liquid form via an endotracheal tube in a single bolus dose as quickly as the neonate tolerates. Some studies recommend the administration of all the surfactant at once while others advocate dividing the bolus into smaller aliquots.

 Another technique of administration known as the INSURE technique is approached with the neonate not already intubated. The INSURE technique uses an in-out intubation procedure to administer the surfactant. This process includes intubation, followed by administration of the drug, and then extubation. Newer methods to limit the invasiveness of older approaches are in practice and targets of research today.[6][7] One such technique is known as the Minimally Invasive Surfactant Therapy or MIST.[8] The MIST method connects the patient to non-invasive respiratory support, and through that, the surfactant administration is with the work of spontaneous breathing. This method is increasingly used to reduce intubation rates and their associated pathologies. Another method is the less invasive surfactant administration or LISA technique.[9] This method utilizes a thin catheter for surfactant delivery, which serves to reduce the possibility of lung injury, as is possible with intubation. At present, five surfactants (lucinactant, colfosceril palmitate, beractant, calefacient, and protectant alfa) have FDA approval. Colfosceril palmitate is no longer commercially available. Lucinactant is the first U.S. FDA-approved protein-containing synthetic surfactant.

The usage of surfactant can lead to bradycardia and hypotension in the neonate. There are also some reports of instances of oxygen desaturation upon administration of the drug. Also, because conventional methods of surfactant administration require an endotracheal tube, certain risks are associated with tubal administration of any drug. Hygiene is of vital importance, especially in neonates, as their immunities are underdeveloped. Infections and sepsis can occur if there are no measures taken to prevent them. Unless the neonate is already intubated, intubation must take place first, which presents with the risk of injury and air leaks. Intubation also poses the risk of airway obstruction, mechanical damage to the airway, and it may require frequent suctioning. There is a risk of alterations in cerebral flow and hypoxemia. Concomitant administration of oxygen can damage lung tissue from oxygen pressure. Excess oxygenation and subsequent cessation of it leads to diseases like bronchopulmonary dysplasia and retrolental fibroplasia in infants as well.[10][11][12]

Since surfactant extraction is from animal sources, a risk of immune activation exists. Rarely the drug can lead to pneumothorax and/or pulmonary hemorrhage. Other side effects may include intraventricular hemorrhage, patent ductus arteriosus, retinopathy, necrotizing enterocolitis, and/or blockage of the endotracheal tube can cause complications as well.

Contraindications to surfactant administration include congenital anomalies that are uncongenial with life, perfusion failure states, diffuse pulmonary hemorrhagic conditions, and a diagnosis of congenital diaphragmatic hernia. Contraindications also include neonates who display respiratory difficulty, but laboratory evidence suggests lung maturity has already occurred. Usage of surfactant appears to result in a deterioration in newborns with pulmonary hypoplasia, although more clinical trials-based evidence is needed.