Nitric oxide for respiratory failure in infants born at or near term

Background Nitric oxide is a major endogenous regulator of vascular tone. Inhaled nitric oxide gas has been investigated as a treatment for persistent pulmonary hypertension of the newborn. Objectives To determine whether treatment of hypoxaemic term and near-term newborn infants with inhaled nitric oxide (iNO) improves oxygenation and reduces the rates of death, the requirement for extracorporeal membrane oxygenation ( ECMO), or affects long term neurodevelopmental outcomes. Search strategy Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. Selection criteria Randomized and quasi-randomized studies of inhaled nitric oxide in term and near term infants with hypoxic respiratory failure. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. Data collection and analysis Trial reports were analysed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. Results of mortality, oxygenation, short term clinical outcomes ( particularly need for ECMO), and long term developmental outcomes were tabulated. Statistics: For categorical outcomes, typical estimates for relative risk and risk difference were calculated. For continuous variables, typical estimates for weighted mean difference were calculated. 95% confidence intervals were used. A fixed effect model was assumed for meta-analysis. Main results Fourteen eligible randomized controlled studies were found in term and near term infants with hypoxia. Seven of the trials compared iNO to control ( placebo or standard care without iNO) in infants with moderate or severe severity of illness scores. Four of the trials compared iNO to control, but allowed back up treatment with iNO if the infants continued to satisfy the same criteria for severity of illness after a defined period of time. Two trials enrolled infants with moderate severity of illness score (OI or AaDO2) and randomized to immediate iNO treatment or iNO treatment only if they deteriorated to more severe criteria. One trial studied only infants with congenital diaphragmatic hernia (Ninos 1997), and one trial enrolled both preterm and term infants (Mercier 1998), but reported the majority of the results separately for the two groups.