Surfactant Replacement Therapy: Beyond Respiratory Distress Syndrome

The absence of surfactant is one of the hallmark features of respiratory distress syndrome (RDS). Surfactant replacement is an effective therapy in the treatment of RDS: up to day, more than 40 clinical trials evaluating the use of surfactant replacement therapy in more than 20,000 enrolled infants showed a major reduction in both mortality and pulmonary air leaks.
Beside RDS, inadequate amount (either by inactivation or inhibition of synthesis) of functional surfactant plays a central role in the pathophysiology of other neonatal diseases, including meconium aspiration syndrome (MAS), shock lung, pulmonary hemorrhage, pneumonia, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). Therefore, surfactant replacement may be a promising therapeutic strategy in these conditions.
For instance, MAS is a serious disease reported in up to 35,000 infants per annum in US: among these babies, 30–50% requires mechanical ventilation and 4-7% die. MAS determines surfactant inactivation, lung inflammation and, eventually, airway obstructions. Of note, surfactant deficiency and parenchymal lung changes may require the use of high ventilatory support and substantial supplemental oxygen, further contributing to lung injury. Two approaches have been attempted to break this vicious circle: surfactant replacement and surfactant lavage.
Surfactant replacement, administered in the same way as in RDS, was applied in some large case series, showing improved oxygenation and decreased ventilatory support. These promising findings were confirmed in randomized clinical trials: beside the improvement in gas exchange, a reduction in the requirement for extracorporeal membrane oxygenation was observed with this strategy.
An alternative approach to treatment is lung lavage with surfactant, which might solubilize meconium and remove it from the lung. The lavage approach was used in some anecdotal experiences, determining a general improvement in MAS infants. These findings were also confirmed in a prospective, randomized controlled trial: lavaged infants had a trend toward faster weaning from mechanical ventilation, and a more rapid decline in the oxygenation index. Moreover, the procedure was well tolerated.
BPD is the occurrence of chronic lung changes following mechanical ventilation. About 30–40% of infants <1,500 g at birth are affected from this disease. Ultimately, BPD results in a decrease in alveolarization and can impair growth and development. Inactivation of surfactant characterizes also BPD,: therefore, surfactant replacement may represent an attractive strategy. Some case series suggested that late administration of surfactant may improve the need for supplemental oxygen and increase ventilatory efficiency. These findings were confirmed in a randomized controlled multicenter trial: overall, treatment of infants at risk for BPD with a standard surfactant-replacement-therapy beginning after the first 2 days of life decreased the need for supplemental oxygen and reduced the rates of death or BPD. In conclusion, the studies and anecdotal experiences available to date suggest that surfactant-replacement therapy can overcome the deficiency states created by inactivation and decreased production which underlies MAS and BPD. However, further and more detailed studies are required to address some unanswered issues, e.g. the optimal administration procedure, the determination of the most suitable patients, and the assessment of long-term outcomes.

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