Elsevier

The Journal of Pediatrics

Volume 170, March 2016, Pages 312-314
The Journal of Pediatrics

Commentary
Recommendations for the Use of Inhaled Nitric Oxide Therapy in Premature Newborns with Severe Pulmonary Hypertension

https://doi.org/10.1016/j.jpeds.2015.11.050Get rights and content

Section snippets

iNO for the Prevention of Bronchopulmonary Dysplasia

iNO is uniquely suited to the treatment of PPHN due to its selectivity for the pulmonary circulation, the absence of toxicities when used at low doses, and its demonstrated efficacy in decreasing the need for treatment with extracorporeal life support.3, 4 The effectiveness of iNO in the near-term and term newborn is largely due to its properties as a selective pulmonary vasodilator; however, numerous laboratory studies also demonstrated other important effects, such as decreasing lung

iNO for the Treatment of Severe PH in the Preterm Infant

Although the focus of the prior randomized, controlled trials was to test the role of iNO in BPD prevention, the potential role for iNO in preterm infants for the acute management of severe hypoxemic respiratory failure has not been fully addressed. In particular, there is a subset of premature newborns with severe PPHN for which iNO may likely be a safe and effective therapy. PPHN in premature newborns (associated with prolonged oligohydramnios, pulmonary hypoplasia, and other causes) is

Controversies

Although the use of iNO in premature infants with PPHN was not addressed in the AAP Statement, the National Institutes of Health Consensus Statement concluded that “there are rare clinical situations, including PH or hypoplasia, that have been inadequately studied in which iNO may have benefit in infants <34 weeks gestation” and that “use in this population should be left to clinical discretion.” Unfortunately, a proper randomized control trial (RCT) of iNO in premature newborns with severe

Recommendations

Based on the above observations, the Pediatric Pulmonary Hypertension Network proposes the following recommendations for the role of iNO in premature newborns:

  • (1)

    iNO therapy should not be used in premature infants for the prevention of BPD, as multicenter studies data have failed to consistently demonstrate efficacy for this purpose;

  • (2)

    iNO therapy can be beneficial for preterm infants with severe hypoxemia that is primarily due to PPHN physiology rather than parenchymal lung disease, particularly if

First page preview

First page preview
Click to open first page preview

References (21)

  • J.C. Mercier et al.

    Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomized controlled trial

    Lancet

    (2010)
  • A. Peliowski et al.

    Inhaled nitric oxide for premature infants after prolonged rupture of the membranes

    J Pediatr

    (1995)
  • J.R. Klinger et al.

    Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension

    Am J Respir Crit Care Med

    (2013)
  • N.N. Finer et al.

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

    Cochrane Database Syst Rev

    (2006)
  • R.H. Clark et al.

    Randomized, controlled trial of low-dose inhaled nitric oxide treatment of persistent pulmonary hypertension of the newborn

    N Engl J Med

    (2000)
  • Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure

    N Engl J Med

    (1997)
  • J.P. Kinsella et al.

    Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease

    Pediatr Res

    (1997)
  • L.D. Nelin et al.

    Nitric oxide increases the survival of rats with a high oxygen exposure

    Pediatr Res

    (1998)
  • Y.J. Lin et al.

    Inhaled nitric oxide enhances distal lung growth after exposure to hyperoxia in neonatal rats

    Pediatr Res

    (2005)
  • D.C. Mccurnin et al.

    Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

    Am J Physiol Lung Cell Mol Physiol

    (2005)
There are more references available in the full text version of this article.

Cited by (0)

Authors are the site PIs and advisory board members for the Pediatric Pulmonary Hypertension Network. J.K., S.A., and R.S. have received honoraria from Scientific Therapeutics Information, Inc, through Ikaria. D.I. and B.H. serve as a consultant for Actelion, Bayer, Eli Lilly, and United Therapeutics, contracted through The University of Colorado and Children's Hospital of Philadelphia, respectively. E.R. has received consulting fees from Actelion, Geliad, and Ikaria, and New York-Presbyterian/Columbia University Medical Center has received grant support from Actelion, Gilead, GlaxoSmithKline, and United Therapeutics. M.M. is the site PI for industry sponsored clinical trials with Ikaria, United Therapeutics, and GlaxoSmithKline. R.S. serves as Associate Editor for The Journal. S.A. serves on the Editorial Board of The Journal. The other authors declare no conflicts of interest.

View full text