Use Of iNO In Infants Research Articles

Inhaled nitric oxide for respiratory failure in preterm infants.

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 specific study in this population. To determine effects of treatment with inhaled nitric oxide (iNO) on death, bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH) or other serious brain injury and on adverse long-term neurodevelopmental outcomes in preterm newborn infants with hypoxic respiratory failure.Owing to substantial variation in study eligibility criteria, which decreases the utility of an overall analysis, we divided participants post hoc into three groups: (1) infants treated over the first three days of life because of defects in oxygenation, (2) preterm infants with evidence of pulmonary disease treated routinely with iNO and (3) infants treated later (after three days of age) because of elevated risk of BPD. We used standard methods of the Cochrane Neonatal Review Group. We searched MEDLINE, Embase, Healthstar and the Cochrane Central Register of Controlled Trials in the Cochrane Library through January 2016. We also searched the abstracts of the Pediatric Academic Societies. Eligible for inclusion were randomised and quasi-randomised studies in preterm infants with respiratory disease that compared effects of iNO gas versus control, with or without placebo. We used standard methods of the Cochrane Neonatal Review Group and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. We found 17 randomised controlled trials of iNO therapy in preterm infants. We grouped these trials post hoc into three categories on the basis of entry criteria: treatment during the first three days of life for impaired oxygenation, routine use in preterm babies along with respiratory support and later treatment for infants at increased risk for bronchopulmonary dysplasia (BPD). We performed no overall analyses.Eight trials providing early rescue treatment for infants on the basis of oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD (typical risk ratio (RR) 0.94, 95% confidence interval (CI) 0.87 to 1.01; 958 infants). Four studies examining routine use of iNO in infants with pulmonary disease reported no significant reduction in death or BPD (typical RR 0.94, 95% CI 0.87 to 1.02; 1924 infants), although this small effect approached significance. Later treatment with iNO based on risk of BPD (three trials) revealed no significant benefit for this outcome in analyses of summary data (typical RR 0.92, 95% CI 0.85 to 1.01; 1075 infants).Investigators found no clear effect of iNO on the frequency of all grades of IVH nor severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH.We found no effect on the incidence of neurodevelopmental impairment. iNO does not appear to be effective as rescue therapy for the very ill preterm infant. Early routine use of iNO in preterm infants with respiratory disease does not prevent serious brain injury or improve survival without BPD. Later use of iNO to prevent BPD could be effective, but current 95% confidence intervals include no effect; the effect size is likely small (RR 0.92) and requires further study.

Inhaled Nitric Oxide in Preterm Infants: A Systematic Review

Studies of the efficacy of inhaled nitric oxide (iNO) to prevent or treat respiratory failure in preterm infants have had variable and contradictory findings. To systematically review the evidence on the use of iNO in infants born at ≤ 34 weeks' gestation who receive respiratory support. Medline, Embase, the Cochrane Central Register of Controlled Studies, PsycInfo, ClinicalTrials.gov, and proceedings of the 2009 and 2010 Pediatric Academic Societies meetings were searched in June 2010. Additional studies from reference lists of eligible articles, relevant reviews, and technical experts were considered. Two investigators independently screened search results and abstracted data from eligible articles. We focus here on mortality, bronchopulmonary dysplasia (BPD), the composite outcome of death or BPD, and neurodevelopmental impairment. Fourteen randomized controlled trials, 7 follow-up studies, and 1 observational study were eligible for inclusion. Mortality rates in the NICU did not differ for infants treated with iNO compared with controls (risk ratio [RR]: 0.97 [95% confidence interval (CI): 0.82-1.15]). BPD at 36 weeks for iNO and control groups also did not differ for survivors (RR: 0.93 [95% CI: 0.86-1.003]). A small difference was found in favor of iNO in the composite outcome of death or BPD (RR: 0.93 [95% CI: 0.87-0.99]). There was no evidence to suggest a difference in the incidence of cerebral palsy (RR: 1.36 [95% CI: 0.88-2.10]), neurodevelopmental impairment (RR: 0.91 [95% CI: 0.77-1.12]), or cognitive impairment (RR: 0.72 [95% CI: 0.35-1.45]). There was a 7% reduction in the risk of the composite outcome of death or BPD at 36 weeks for infants treated with iNO compared with controls but no reduction in death alone or BPD. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.

The role of nitric oxide in hyperoxia-induced injury to the developing lung.

Exogenous or inhaled NO (iNO) has been successfully used, as a selective pulmonary vasodilator, in a wide variety of clinical situations especially in the management of persistent pulmonary hypertension in the newborn. A better understanding of the role of endogenous and exogenous NO in the lungs of surfactant-deficient animals exposed to hyperoxia could result in novel strategies for the better management of RDS in premature babies with the ultimate aim to decrease chronic lung disease in these infants. This review will focus on the effects of NO, when used in combination with hyperoxia, on lung injury; information on the effects on cell culture systems and animal models will be used to highlight the unique responses of the developing lung. Most of the data from cell culture systems and adult animal models of hyperoxia-induced lung injury suggests that endogenous NO has a protective role. In the newborn animal, endogenous NO appeared to be harmful, had no effect or was protective in hyperoxia-induced lung injury. The data are conflicting on the issue of whether exogenous NO is protective or damaging in the presence of hyperoxia on lung cells and animal models. Despite the variability in the studies, it would appear that low dose exogenous NO for short duration is beneficial in hyperoxic lung injury in adult and newborn animals. In the human newborn, use of iNO in infants< 34 weeks of gestation should be considered experimental, pending results of ongoing trials.