Surfactant use for neonatal lung injury: beyond respiratory distress syndrome

Abstract

Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.