When to say no to inhaled nitric oxide in neonates?

Semin Fetal Neonatal Med. 2021 Apr;26(2):101200. doi: 10.1016/j.siny.2021.101200. Epub 2021 Jan 22.


Inhaled nitric oxide (iNO) was approved for use in critically ill term and near-term neonates (>34 weeks gestational age) in 1999 for hypoxic respiratory failure (HRF) with evidence of pulmonary hypertension. In 2011 and 2014, the National Institutes of Health and American Academy of Pediatrics respectively recommended against the use of iNO in preterm infants <34 weeks. However, these guidelines were based on trials conducted with varying inclusion criteria and outcomes. Recent guidelines from the American Thoracic Society/American Heart Association, the Pediatric Pulmonary Hypertension Network (PPHNet) and European Pediatric Pulmonary Vascular Disease Network recommend the use of iNO in preterm neonates with HRF with confirmed pulmonary hypertension. This review discusses the available evidence for off-label use of iNO. Preterm infants with prolonged rupture of membranes and pulmonary hypoplasia appear to respond to iNO. Similarly, preterm infants with physiology of pulmonary hypertension with extrapulmonary right-to-left shunts may potentially have an oxygenation response to iNO. An overview of relative and absolute contraindications for iNO use in neonates is provided. Absolute contraindications to iNO use include a ductal dependent congenital heart disease where systemic circulation is supported by a right-to-left ductal shunt, severe left ventricular dysfunction and severe congenital methemoglobinemia. In preterm infants, we do not recommend the routine use of iNO in HRF due to parenchymal lung disease without pulmonary hypertension and prophylactic use to prevent bronchopulmonary dysplasia. Future randomized trials evaluating iNO in preterm infants with pulmonary hypertension and/or pulmonary hypoplasia are warranted. (233/250 words).

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Administration, Inhalation
  • Bronchopulmonary Dysplasia* / drug therapy
  • Child
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Nitric Oxide*
  • Vasodilator Agents / therapeutic use


  • Vasodilator Agents
  • Nitric Oxide