Skip to main content

Advertisement

SpringerLink
Log in

Use of Inhaled Nitric Oxide in Preterm Infants: Is There Sufficient Evidence?

  • Review Article
  • Published:
Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Nitric oxide (NO) is a potent vasodilator. The inhaled form (iNO) improves outcomes in term infants with persistent pulmonary hypertension of the newborn (PPHN) or bronchopulmonary dysplasia-associated pulmonary hypertension in preterm infants. However, in preterm infants, the risks and benefits of iNO use are controversial. Substantial evidence reveals no significant impact on survival or other morbidities in preterm infants with iNO treatment, independent of indication, timing, or duration of use. Many scientific organizations do not recommend the use of iNO in preterm infants, except in unique clinical circumstances with echocardiographic findings of PPHN in the setting of presumed pulmonary hypoplasia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Soraisham AS, Harabor A, Shivananda S, et al. Trends and Variations in the use of inhaled nitric oxide in preterm infants in canadian neonatal intensive care units. Am J Perinatol. 2016;33:715–22.

    Article  Google Scholar 

  2. Cole FS, Alleyne C, Barks JD, et al. NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants. Pediatrics. 2011;127:363–9.

    Article  Google Scholar 

  3. Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev. 2017;1:CD000399.

  4. Kumar P, Committee on Fetus, Newborn, American Academy of Pediatrics. Use of inhaled nitric oxide in preterm infants. Pediatrics. 2014;133:164–70.

  5. Kinsella JP, Parker TA, Galan H, Sheridan BC, Halbower AC, Abman SH. Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease. Pediatr Res. 1997;41:457–63.

    Article  CAS  Google Scholar 

  6. Walther FJ, Benders MJ, Leighton JO. Early changes in the neonatal circulatory transition. J Pediatr. 1993;123:625–32.

    Article  CAS  Google Scholar 

  7. Abman SH, Hansmann G, Archer SL, et al. Pediatric Pulmonary Hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037–99.

    Article  Google Scholar 

  8. Kinsella JP, Steinhorn RH, Krishnan US, et al. Recommendations for the use of inhaled nitric oxide therapy in premature newborns with severe pulmonary hypertension. J Pediatr. 2016;170:312–4.

    Article  Google Scholar 

  9. Askie LM, Ballard RA, Cutter GR, et al. Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials. Pediatrics. 2011;128:729–39.

    Article  Google Scholar 

  10. Hasan SU, Potenziano J, Konduri GG, et al. Effect of inhaled nitric oxide on survival without bronchopulmonary dysplasia in preterm infants: a randomized clinical trial. JAMA Pediatr. 2017;171:1081–9.

    Article  Google Scholar 

  11. Mourani PM, Ivy DD, Gao D, Abman SH. Pulmonary vascular effects of inhaled nitric oxide and oxygen tension in bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2004;170:1006–13.

    Article  Google Scholar 

  12. Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003;349:2099–107.

    Article  CAS  Google Scholar 

  13. Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med. 2005;353:23–32.

    Article  CAS  Google Scholar 

  14. Chandrasekharan P, Lakshminrusimha S, Chowdhury D, et al. Early hypoxic respiratory failure in extreme prematurity: mortality and neurodevelopmental outcomes. Pediatrics. 2020;146:e20193318.

  15. Peliowski A, Finer NN, Etches PC, Tierney AJ, Ryan CA. Inhaled nitric oxide for premature infants after prolonged rupture of the membranes. J Pediatr. 1995;126:450–3.

    Article  CAS  Google Scholar 

  16. Chock VY, Van Meurs KP, Hintz SR, et al. Inhaled nitric oxide for preterm premature rupture of membranes, oligohydramnios, and pulmonary hypoplasia. Am J Perinatol. 2009;26:317–22.

    Article  Google Scholar 

  17. Ahmed MS, Giesinger RE, Ibrahim M, et al. Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxic preterm neonates. J Paediatr Child Health. 2019;55:753–61.

    PubMed  Google Scholar 

  18. Carey WA, Weaver AL, Mara KC, Clark RH. Inhaled nitric oxide in extremely premature neonates with respiratory distress syndrome. Pediatrics. 2018;141:e20173108.

  19. Van Meurs KP, Wright LL, Ehrenkranz RA, et al. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med. 2005;353:13–22.

    Article  Google Scholar 

  20. Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2017;1:CD000509.

  21. Barrington KJ, Finer NN. Inhaled nitric oxide for preterm infants: a systematic review. Pediatrics. 2007;120:1088–99.

    Article  Google Scholar 

  22. Weinberger B, Laskin DL, Heck DE, Laskin JD. The toxicology of inhaled nitric oxide. Toxicol Sci. 2001;59:5–16.

    Article  CAS  Google Scholar 

  23. Peliowski A, Canadian Paediatric Society Fetus, Newborn Committee. Inhaled nitric oxide use in newborns. Paediatr Child Health. 2012;17:95–100.

  24. Manja V, Guyatt G, Lakshminrusimha S, et al. Factors influencing decision making in neonatology: inhaled nitric oxide in preterm infants. J Perinatol. 2019;39:86–94.

    Article  Google Scholar 

  25. Soll RF. Inhaled nitric oxide for preterm infants: what can change our practice? Pediatrics. 2018;141:e20174214.

  26. Shiraishi J, Kusuda S, Cho K, et al. Standardization of nitric oxide inhalation in extremely preterm infants in Japan. Pediatr Int. 2019;61:152–7.

    Article  CAS  Google Scholar 

  27. Shah DM, Kluckow M. Early functional echocardiogram and inhaled nitric oxide: usefulness in managing neonates born following extreme preterm premature rupture of membranes (PPROM). J Paediatr Child Health. 2011;47:340–5.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Foothills Medical Centre, 780-1403 29th St NW, Calgary, AB T2N 2T9, Canada

    Amelie Stritzke & Abhay Lodha

  2. Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Canada

    Amelie Stritzke

  3. Alberta Health Services, Calgary, Canada

    Amelie Stritzke & Abhay Lodha

  4. Department of Pediatrics, Division of Neonatology, The Children’s Regional Hospital at Cooper, Camden, NJ, USA

    Vineet Bhandari

  5. Department of Community Health Sciences, University of Calgary, Calgary, Canada

    Abhay Lodha

  6. Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada

    Abhay Lodha

Authors
  1. Amelie Stritzke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vineet Bhandari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abhay Lodha
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AS drafted and revised the manuscript; VB reviewed and revised the final manuscript; AL conceptualized the manuscript, drafted, reviewed, and revised the final manuscript. AL is the guarantor for this paper.

Corresponding author

Correspondence to Amelie Stritzke.

Ethics declarations

Conflict of Interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stritzke, A., Bhandari, V. & Lodha, A. Use of Inhaled Nitric Oxide in Preterm Infants: Is There Sufficient Evidence?. Indian J Pediatr 89, 262–266 (2022). https://doi.org/10.1007/s12098-021-03827-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-021-03827-0

Keywords

Search

Navigation