Artificial surfactant linked to significant improvement of RDS [Pediatrics Classics Series]

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1. Among 10 infants treated for respiratory distress syndrome with artificial surfactant in this landmark trial, significant improvements in blood pressure, acid-base status, arterial oxygenation, and radiologic findings were observed.

2. Infants also required significantly less oxygen therapy and ventilator pressure following surfactant administration.

Original Date of Publication: January 1980

Study Rundown: Hyaline membrane disease (HMD), now known as infant respiratory distress syndrome (RDS), is a pulmonary disease of young infants most often linked to fetal immaturity. After the landmark 1959 discovery by Avery et al. connecting insufficient surfactant with RDS, methods of treating the disease were investigated. As surfactant was known to reduce lung surface tension, making it easier to maintain patent alveoli, this study built upon work in animals as the first trial of artificial surfactant treatment for RDS in human infants. Using a mixture of natural and synthetic lipids including dipalmitoyl lethicin (the primary component of surfactant) and phosphatidyl glycerol, researchers administered artificial surfactant to 10 infants diagnosed with RDS and examined their laboratory, clinical examination, and radiologic changes. Significant reductions in systolic blood pressure (SBP), along with improvements in arterial oxygenation, arterial-alveolar oxygen concentration differences, acid-base balance, and radiologic findings were seen. Infants also required significantly less inspired oxygen and ventilator pressure after surfactant administration. This study was limited by a lack of randomization, comparison to control infants, and its small sample size. Despite these limitations, this study led to future, large, randomized, clinical trials that further solidified the benefits of artificial surfactant use among infants with RDS. Antenatal corticosteroids coupled with post-delivery surfactant and ventilation are now commonplace treatments for infants in neonatal intensive care and have been proven to significantly improve clinical outcomes among infants suffering from poor lung development.

Click to read the study in The Lancet

Click to read the 1959 study referenced above published in JAMA Pediatrics

In-Depth [prospective cohort study]: Ten infants with diagnosed RDS (mean gestational age = 30.2 weeks, mean birthweight = 1552 g) were included in the study. Prior to surfactant administration, ventilator settings were noted and not changed. Arterial oxygen tension (P_aO₂), carbon dioxide tension (P_aCO₂), and pH were recorded 30-90 minutes before and again 10-20 minutes before surfactant administration to provide a snapshot of each infant’s physiologic state. No significant differences were noted between these 2 time periods. About 10 mL of artificial surfactant (150 μmol lipid phosphorus/kg) was suspended in normal saline and put into the infants’ endotracheal tubes. Infants were then moved into different positions to ensure the solution was distributed to each lung segment and the infant was ventilated with a respirator. Up to 3 hours post-administration P_aO₂, PaCO₂, acid-base balance, and radiographic findings were assessed without alteration in ventilator settings. Following this assessment, ability to reduce inspired oxygen concentration (F_iO₂) and respiratory pressure were noted.

On clinical examination, significant increases in SBP post-administration was observed in the 6 infants who had continuous blood pressure monitoring (37 + 5 mmHg pre v. 59 + 4 mmHg post, p < 0.02). PO₂ increased significantly (45 + 7 mmHg pre v. 212 + 46 mmHg post, p < 0.005), PCO₂ decreased significantly (50 + 4 mmHg pre v. 33 + 2 mm Hg post, p < 0.005), and pH increased significantly (7.13 + 0.05 pre v. 7.31 + 0.04, p < 0.05). Three hours post-administration, F_iO₂ were able to decrease significantly from 81 + 7% to 38 + 5% (p < 0.01) and, within 6 hours of administration, inspiratory pressure could be reduced from 30 + 2 cm H₂O to 22 + 2 cm H₂O (p < 0.02). The difference in alveolar and arterial O₂ concentration decreased significantly as well 474 + 49 mmHg to 189 + 29 (p < 0.005) 3 hours post-administration and to 120 + 18 mmHg (p < 0.001) 30 hours post-administration. At an average of 6 hours post-administration complete radiologic resolution of RDS was observed. Two of the 10 infants studied died due to causes unrelated to RDS or surfactant administration. No serious adverse events were linked to surfactant use.

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