Inhaled Nitric Oxide for Respiratory Failure in Preterm Infants
ABSTRACT Background: Inhaled nitric oxide (iNO) is effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure and the potential risks of iNO differ substantially in preterm infants, necessitating study in this population. Objectives: To determine the effect of treatment with iNO on death, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and neurodevelopmental disability in preterm newborn infants with respiratory disease. Search Methods: Standard methods of the Cochrane Neonatal Review Group were used. MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (The Cochrane Library) were searched covering the years from 1985 to 2010. In addition, the abstracts of the Pediatric Academic Societies were also searched. Selection Criteria: Randomized and quasi-randomized studies in preterm infants with respiratory disease that compared the effects of iNO gas to control, with or without placebo were eligible. Data Collection and Analysis: Standard methods of the Cochrane Neonatal Review Group were used. Main Results: Fourteen randomized controlled trials of iNO therapy in preterm infants were found. The trials have been grouped post hoc into three categories depending on entry criteria: entry in the first 3 days of life based on oxygenation criteria, routine use in preterm babies with pulmonary disease, and later enrolment based on an increased risk of BPD. No overall analyses were performed. Nine trials of early rescue treatment of infants based on oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD. Three studies with routine use of iNO in infants with pulmonary disease also demonstrated no significant reduction in death or BPD [typical RR 0.93 (95% CI 0.86-1.01)] although this small effect approached significance. Later treatment with iNO based on the risk of BPD (two trials) demonstrated no significant benefit for this outcome in analyses which are possible using summary data. There is no clear effect of iNO on the frequency of all grades of IVH or of severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH. No effect on the incidence of neurodevelopmental impairment was found.
- SourceAvailable from: Rajesh Alphonse
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- "Inhaled NO is a potent pulmonary vasodilator and promotes distal lung growth. Inhaled NO shows promise as a prophylactic therapy to decrease the incidence of BPD in experimental models –, while results in preterm infants remain inconclusive . Thus, we hypothesized that H2S would have similar beneficial effects on distal lung growth and PHT. "
ABSTRACT: Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT). Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S), carbon monoxide and nitric oxide (NO), belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD. We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) to study its lung protective potential in vitro and in vivo. In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation. H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.PLoS ONE 03/2014; 9(3):e90965. DOI:10.1371/journal.pone.0090965 · 3.23 Impact Factor
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