Inhaled Nitric Oxide Therapy in the Preterm Infant Who Has Respiratory Distress Syndrome

Abstract

After completing this article, readers should be able to: 1. Delineate the rationale for inhaled nitric oxide (iNO) use in respiratory distress syndrome. 2. List the toxicities of iNO. 3. Describe the primary findings of iNO therapy in major clinical trials. Respiratory distress syndrome (RDS) has been a major factor determining the limits of viability in the preterm infant. RDS is, in large part, the result of surfactant deficiency. Surfactant replacement and antenatal steroid use are the two major advances in the treatment of RDS to date and have resulted in significant decreases in mortality and chronic lung disease (CLD). Surfactant replacement became widely available in 1991, and antenatal steroids achieved widespread use following the National Institutes of Health Consensus Conference in 1994. (1) However, substantial mortality and CLD still are seen in the very low-birthweight infant (Fig. 1). Figure 1 National Institute of Child and Human Development (NICHD) Neonatal Research Network mortality and CLD rates for 2003 in preterm infants born at 23 to 30 weeks’ gestation. Following the identification of nitric oxide (NO) as the vascular endothelial relaxing factor, use of the agent has moved rapidly from bench to bedside. Inhaled nitric oxide (iNO) was found to improve oxygenation in adult and pediatric patients who had hypoxic respiratory failure. (2)(3)(4) Subsequent randomized, controlled trials in term and near-term infants who had hypoxic respiratory failure demonstrated an improvement in oxygenation as well as a significant decrease in death or the need for extracorporeal membrane oxygenation. (5)(6)(7) Following United States Food and Drug Administration review of these trials, iNO was approved for use in term and near-term infants who had hypoxic respiratory failure. The role of iNO in the preterm infant who has RDS has been an active area of investigation over the last decade. This …