No abstract

We compared the effects of surfactant and partial liquid ventilation (PLV), and the impact of administration order, on oxygenation, respiratory system compliance (Crs), hemodynamics, and lung pathology in an animal lung injury model. We studied four groups: surfactant alone (S; n = 8); partial liquid ventilation alone (PLV-only; n = 8); surfactant followed by partial liquid ventilation (S-PLV; n = 8); and partial liquid ventilation-followed by surfactant (PLV-S; n = 8). Following treatments, all animals had improved oxygenation index (OI) and Crs. Animals in PLV groups showed continued improvement over 2 h (% change OI: PLV-S -83% versus S -47%, p < 0.05; % change Crs: S-PLV 73% versus S 13%, p < 0.05). We also saw administration-order effects: surfactant before PLV improved Crs (0.92 ml/cm H2O after surfactant versus 1.13 ml/cm H2O after PLV, p < 0.02) without changing OI, whereas surfactant after PLV did not change Crs and OI increased (5.01 after PLV versus 8.92 after surfactant, p < 0.03). Hemodynamics were not different between groups. Pathologic analysis demonstrated decreased lung injury in dependent lobes of all PLV-treated animals, and in all lobes of S-PLV animals, when compared with the lobes of the S animals (p < 0.05). We conclude that surfactant therapy in combination with PLV improved oxygenation, respiratory system mechanics, and lung pathology to a greater degree than surfactant therapy alone. Administration order affected initial physiologic response and ultimate pathology: surfactant given before PLV produced the greatest improvements in pathologic outcomes.

Objectives To assess whether late surfactant treatment of extremely low gestational age newborn (ELGAN) infants requiring ventilation at 7–14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Study design ELGAN infants (≤ 28 0/7 weeks) who required mechanical ventilation at 7–14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide (INO) and either surfactant (calfactant/Infasurf®) or sham instillation every 1–3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, evaluated by physiologic oxygen/flow reduction. Results Between January 2010 and September 2013, 511 infants were enrolled. There were no differences between treatment groups in mean birth weight (701±164 g), gestational age (25.2±1.2 weeks), percentage <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 weeks PMA (31.3% vs. 31.7%; relative benefit 0.98 (95% CI: 0.75, 1.28 p=0.89) or 40 weeks (58.7% vs. 54.1%; relative benefit 1.08:0.92, 1.27 p=0.33). There were no differences between groups in serious adverse events, co-morbidities of prematurity, nor in the severity of lung disease to 36 weeks. Conclusions Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving iNO was well tolerated but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing.

In this animal model, partial liquid ventilation using conventional or high-frequency ventilation provided rapid and sustained improvements in oxygenation without adverse hemodynamic consequences. Animals treated with partial liquid ventilation-flow interruption had a significantly decreased survival rate vs. animals treated with the other studied techniques. Histopathologic and morphometric analysis showed significantly less injury in the lower lobes of lungs from animals treated with partial liquid ventilation. High-frequency ventilation techniques did not further improve pathologic outcome.