Surfactant treatment in acute respiratory distress syndrome

Neonatal respiratory failure is based upon deficiency of primary surfactant and inactivation of the surfactant itself as a result of plasma proteins leaking into the airways from areas of epithelial disruption and injury. Moreover, various pre- and postnatal factors, such as exposure to chorioamnionitis, pneumonia, sepsis and asphyxia, induce an injurious inflammatory response in preterm infants, therefore impairing surfactant function, synthesis and alveolar stability. Surfactant inactivation and dysfunction have also been shown to be important features in acute respiratory failure of near-term and term newborn infants with meconium aspiration syndrome (MAS), bacterial pneumonia and pulmonary hemorrhage.
Surfactant treatment in preterm infants and term newborns with ARDS (acute respiratory distress syndrome)-like severe respiratory failure can substitute a primary surfactant deficiency and counterbalance surfactant inactivation or inhibition. The practical consequences of this strategy would be to treat infants initially with a higher single dose of surfactant preparation (for example, porcine surfactant up to 200 mg per kg body weight) and/or to use repetitive doses in 6 to 12 h intervals (each ˜100 mg/kg).
This approach gave promising results in different clinical observations. For instance, in preterm infants with group B streptococcal pneumonia, surfactant administration improved gas exchange, therefore suggesting that there should be no concerns about treating preterm or term infants with sepsis/pneumonia syndromes and respiratory failure with surfactant. Of note, a high amount of phospholipids and SP-B would be preferable to avoid possible adverse effects observed with high-volume preparations. Other possible indications for treatment of respiratory failure in preterm infants have been reported: surfactant replacement improved oxygenation and gas exchange in preterm infants with respiratory failure who had been transferred from peripheral pediatric hospitals at a postnatal age of >15 h. In addition, preterm infants with pulmonary hemorrhage responded with an improvement in oxygenation after surfactant substitution and no baby deteriorated after surfactant administration. Similarly, preterm infants with signs of early chronic lung disease had a decreased oxygen requirement within 1 h after surfactant administration.
Surfactant administration determined important clinical benefits in infants with MAS. In a randomized trial, surfactant administration reduced air leaks, extracorporeal membrane oxygenation (ECMO) requirement and days on oxygen and mechanical ventilation; these benefits occurred after the newborns had received a high cumulative dose of surfactant (˜300 mg/kg). These results were overall confirmed in another randomized trial. It must me emphasized that no effect of surfactant therapy on the risk of pneumothorax and mortality was described in the two studies, while the relative risk for ECMO was overall significantly reduced to 0.64.
In conclusion, although for the majority of suggested indications no data exist from randomized controlled trials, surfactant replacement therapy seems to improve oxygenation and lung function in many infants with ARDS without any apparent negative side effect.

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