Issue 5 – September 2018

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that can improve smooth muscle relaxation leading to increased blood flow through the lungs and improved oxygenation.

There is evidence that iNO benefits infants with hypoxic respiratory failure born at or near term, but little to no evidence that rescue or routine use of iNO benefits preterm infants.

Of 1018 NICUs responding to the 2017 membership survey, 73% reported having iNO. Of those, 71% were in the United States, 64% were teaching hospitals, 22% were Type C hospitals which do cardiac surgery requiring bypass, and 51% were Type B hospitals which do surgery but not cardiac surgery requiring bypass.

Among centers that reported having iNO, 75% of these centers used iNO with at least one infant who were 22 to 29 weeks’ gestational age at birth. On average, 8% of infants 22 to 29 weeks at these centers received iNO. The median hospital rate of iNO use among infants 22 to 29 weeks was 6% (25th percentile: 0%; 75th percentile: 12%).

Use of inhaled nitric oxide in preterm infants continues despite little evidence of effectiveness from trials or meta-analyses(1,2) and statements from the National Institutes of Health and the American Academy of Pediatrics discouraging its use(3,4).

The National Institutes of Health Consensus Statement has room for interpretation for use in patients with persistent pulmonary hypertension (PPHN) or pulmonary hypoplasia(3), and other organizations including the American Heart Association and American Thoracic Society have suggested that inhaled nitric oxide can be beneficial for preterm infants with PPHN(5). The neonatal community would be well served by rigorous randomized trials testing inhaled nitric oxide against standard of care for infants with PPHN. Registries of infants with PPHN may help elucidate differences in practices and outcomes.

Until then, consider this: If a single inhaled nitric oxide session costs $100,000 per infant, in 2017, centers reporting inhaled nitric oxide use in infants 22 to 29 weeks gestational age spent nearly $300,000,000 on an unproven therapy. As we progress in this era of value-based care, the value of inhaled nitric oxide should be considered with the risks and benefits to patients and families.

1. Barrington KJ, Finer N. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2010;(12):CD000509.
2.  Askie LM, Ballard RA, Cutter GR, et al; Meta-analysis of Preterm Patients on Inhaled Nitric Oxide Collaboration. Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials. Pediatrics. 2011;128(4):729–739.
3. Cole FS, Alleyne C, Barks JD, et al. NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants. Pediatrics. 2011;127(2):363–369.
4. Kumar P; Committee on Fetus and Newborn; American Academy of Pediatrics. Use of inhaled nitric oxide in preterm infants. Pediatrics. 2014;133(1):164–170.
5. Abman SH, Hansmann G, Archer SL, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; American Thoracic Society. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society [published correction appears in Circulation. 2016;133(4):e368]. Circulation. 2015;132(21):2037–2099.

This report is made possible by Vermont Oxford Network members who voluntarily contribute data in a global effort to improve the care of high-risk newborns. VON members can view center-specific data by logging on to Nightingale and benchmark against this NICU by the Numbers report.

Editors: Erika Edwards, PhD, MPH; Roger Soll, MD

Analyst: Lucy Greenberg, MS