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Objective: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control)., Study Design: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys)., Results: Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM., Conclusion: Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD)., Study Design: Extremely low GA newborn infants (GA ≤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 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, as evaluated by physiological oxygen/flow reduction., Results: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks., Conclusion: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial., Methods: We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age., Results: Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were similar. The rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was 43.9 percent in the group receiving nitric oxide and 36.8 percent in the placebo group (P=0.042). The infants who received inhaled nitric oxide were discharged sooner (P=0.04) and received supplemental oxygen therapy for a shorter time (P=0.006). There were no short-term safety concerns., Conclusions: Inhaled nitric oxide therapy improves the pulmonary outcome for premature infants who are at risk for bronchopulmonary dysplasia when it is started between 7 and 21 days of age and has no apparent short-term adverse effects. (ClinicalTrials.gov number, NCT00000548 [ClinicalTrials.gov] .)., (Copyright 2006 Massachusetts Medical Society.)

Arguably one of the most important advances in critical care medicine in recent years has been the understanding that mechanical ventilators can impart harm and that lung-protective ventilation strategies can save lives. High-frequency oscillatory ventilation appears ideally suited for lung protection at first glance. Two camps of opinion exist, however, even in neonates where this modality has been most extensively studied. In the present debate, the prevailing arguments from each of those camps are made available for the reader to decide.

Background: The efficacy and safety of early high-frequency oscillatory ventilation as compared with conventional synchronized intermittent mandatory ventilation for the treatment of infants with very low birth weight have not been established., Methods: We conducted a randomized, multicenter clinical trial to determine whether infants treated with early high-frequency oscillatory ventilation were more likely than infants treated with synchronized intermittent mandatory ventilation to be alive without requiring supplemental oxygen at 36 weeks of postmenstrual age. Eligible infants weighed 601 to 1200 g at birth, were less than four hours of age, had received one dose of surfactant, and required ventilation with a mean airway pressure of at least 6 cm of water and a fraction of inspired oxygen of at least 0.25. Infants were stratified according to birth weight and exposure to prenatal corticosteroids and then randomly assigned to high-frequency oscillatory ventilation or synchronized intermittent mandatory ventilation. Ventilation was managed according to protocols designed to optimize lung inflation and blood gas values., Results: Five hundred infants were enrolled in the study. Infants randomly assigned to high-frequency oscillatory ventilation were successfully extubated earlier than infants assigned to synchronized intermittent mandatory ventilation (P<0.001). Of infants assigned to high-frequency oscillatory ventilation, 56 percent were alive without a need for supplemental oxygen at 36 weeks of postmenstrual age, as compared with 47 percent of those receiving synchronized intermittent mandatory ventilation (P=0.046). There was no difference between the groups in the risk of intracranial hemorrhage, cystic periventricular leukomalacia, or other complications., Conclusions: There was a small but significant benefit of high-frequency oscillatory ventilation in terms of the pulmonary outcome for very-low-birth-weight infants without an increase in the occurrence of other complications of premature birth., (Copyright 2002 Massachusetts Medical Society)