Clinical Trials of Inhaled Nitric Oxide Therapy in the Newborn

Abstract

1. John P. Kinsella, MD* 1. 2. *Pediatric Heart Lung Center and the Section of Neonatology, Department of Pediatrics, The University of Colorado School of Medicine and The Children’s Hospital, Denver, CO. After completing this article, readers should be able to: 1. Describe the benefits of inhaled nitric oxide in the treatment of persistent pulmonary hypertension of the newborn. 2. Determine the range of appropriate initial doses of inhaled nitric oxide therapy for term neonates. 3. Delineate the potential role of inhaled nitric oxide in conjunction with extracorporeal membrane oxygenation. 4. Describe the lung-specific effects of low-dose inhaled nitric oxide therapy in preterm newborns who have severe hypoxemic respiratory failure. Early reports of the use of inhaled nitric oxide (iNO) in term newborns who had persistent pulmonary hypertension showed both acute and sustained improvement in oxygenation. Subsequently, randomized controlled trials of iNO in term newborns confirmed that this selective pulmonary vasodilator improves oxygenation and reduces the need for extracorporeal membrane oxygenation (ECMO). Results of a more recent randomized controlled trial of iNO in term newborns corroborate the findings of previous studies. These studies should provide sufficient evidence of the safety and efficacy of iNO to support regulatory approval of this therapy for persistent pulmonary hypertension of the newborn (PPHN). However, less is known about the potential role of iNO in preterm newborns. In this review, we summarize the key findings of clinical trials in the term newborn and the current status of iNO in the preterm newborn. After the publication of pilot trials with iNO, which documented marked improvement in oxygenation in term newborns who had PPHN, several randomized, controlled trials were conducted and demonstrated further the efficacy of iNO in PPHN. For example, these studies reported acute improvement in oxygenation after 30 minutes of iNO treatment. iNO reduced the need for ECMO, and lung recruitment strategies augmented the response to iNO when PPHN complicated the course of patients who had parenchymal lung disease. However, none of the studies was designed to evaluate the efficacy of …