A quality improvement project improving the value of iNO utilization in preterm and term infants



Inhaled NO (iNO) is used in the NICU for management of hypoxemic respiratory failure. The cost of iNO is significant and does not consistently improve outcomes in infants <34 weeks.

Project design

Our team used The Model for Improvement to design a quality improvement project to utilize iNO for appropriate indications, ensure response to therapy and initiate timely weaning. The project was carried out at a Level IV NICU and successful interventions spread to a smaller Level III NICU.


This project demonstrated significant improvement in all measures; total iNO hours per month, average iNO hours per patient, and the percentage of prolonged iNO courses. With an estimated cost of $115/h, the cost per patient for iNO use declined by half from $21,620 to $10,580.


Our team improved the value of iNO utilization at our institution and spread successful interventions to another NICU in our network.

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Fig. 1: iNO management guideline.
Fig. 2: Total iNO hours per month for term (a) and preterm (b) infants.
Fig. 3: Average iNO hours per patient per month for term (a) and preterm (b) infants.
Fig. 4: Percentage of prolonged iNO courses > 120 h per month for term (a) and preterm (b) infants.


  1. 1.

    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.

    PubMed  Google Scholar 

  2. 2.

    Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2017;1:Cd000509.

    PubMed  Google Scholar 

  3. 3.

    Witzmann K. Medical officer review: INOmax; 2010. https://www.fda.gov/media/80208/download.

  4. 4.

    Cole FS, Alleyne C, Barks JD, Boyle RJ, Carroll JL, Dokken D, et al. NIH consensus development conference: inhaled nitric oxide therapy for premature infants. NIH Consens State Sci Statements. 2010;27:1–34.

    PubMed  Google Scholar 

  5. 5.

    Kumar P. Use of inhaled nitric oxide in preterm infants. Pediatrics. 2014;133:164–70.

    Article  Google Scholar 

  6. 6.

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

    Article  Google Scholar 

  7. 7.

    Ellsworth MA, Harris MN, Carey WA, Spitzer AR, Clark RH. Off-label use of inhaled nitric oxide after release of NIH consensus statement. Pediatrics. 2015;135:643–8.

    Article  Google Scholar 

  8. 8.

    Watson RS, Clermont G, Kinsella JP, Kong L, Arendt RE, Cutter G, et al. Clinical and economic effects of iNO in premature newborns with respiratory failure at 1 year. Pediatrics. 2009;124:1333–43.

    Article  Google Scholar 

  9. 9.

    Lorch SA, Cnaan A, Barnhart K. Cost-effectiveness of inhaled nitric oxide for the management of persistent pulmonary hypertension of the newborn. Pediatrics. 2004;114:417–26.

    Article  Google Scholar 

  10. 10.

    Elmekkawi A, More K, Shea J, Sperling C, Da Silva Z, Finelli M, et al. Impact of Stewardship on inhaled nitric oxide utilization in a neonatal ICU. Hosp Pediatr. 2016;6:607–15.

    Article  Google Scholar 

  11. 11.

    Todd Tzanetos DR, Housley JJ, Barr FE, May WL, Landers CD. Implementation of an inhaled nitric oxide protocol decreases direct cost associated with its use. Respir Care. 2015;60:644–50.

    Article  Google Scholar 

  12. 12.

    Hughes Driscoll CA, Davis NL, Miles M, El-Metwally D. A quality improvement project to improve evidence-based inhaled nitric oxide use. Respir Care. 2018;63:20–7.

    Article  Google Scholar 

  13. 13.

    Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006;355:343–53.

    Article  CAS  Google Scholar 

  14. 14.

    Askie LM, Ballard RA, Cutter GR, Dani C, Elbourne D, Field D, 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 

  15. 15.

    Donohue PK, Gilmore MM, Cristofalo E, Wilson RF, Weiner JZ, Lau BD, et al. Inhaled nitric oxide in preterm infants: a systematic review. Pediatrics. 2011;127:e414–22.

    Article  Google Scholar 

  16. 16.

    Langley GJ. The improvement guide a practical approach to enhancing organizational performance. 2nd ed. Jossey-Bass: San Francisco; 2009. pp. 1. online resource (xxi, 490 p.).

  17. 17.

    Nolan TRR, Haraden C, Griffin FA. Improving the Reliability of Healthcare. In: IHI innovation series white paper Boston. Institute for Healthcare Improvement; 2004. www.ihi.org.

  18. 18.

    Provost LP, Murray SK. The health care data guide learning from data for improvement. 1st ed. Jossey-Bass: San Francisco, CA; 2011. pp. 1. online resource (xxviii, 445 pages).

  19. 19.

    Karsies TJ, Evans L, Frost R, Ayad O, McClead R. A quality improvement initiative to standardize use of inhaled nitric oxide in the PICU. Pediatr Qual Saf. 2017;2:e011.

    Article  Google Scholar 

  20. 20.

    Dukhovny D, Pursley DM, Kirpalani HM, Horbar JH, Zupancic JA. Evidence, quality, and waste: solving the value equation in neonatology. Pediatrics. 2016;137:e20150312.

    Article  Google Scholar 

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The authors thank to Lloyd P Provost, MS for assistance with data transformation and review of paper.

Author information




HF and TS conceptualized the study design, collected and analyzed data, implemented interventions, drafted, reviewed, and revised the paper. LD, SD, OO, TR, SS, and ST participated in designing and testing interventions, analyzing data, drafting, and reviewing the paper. All authors approved the final paper as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Hannah Fischer.

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The authors declare that they have no conflict of interest.

Ethical approval

This project was determined to be nonhuman subjects research by the University of Louisville Institutional Review Board and Norton Children’s Hospital Research Board. Balancing measures monitored for prevention of patient harm included mortality, escalation of care to ECMO, the number of infants requiring reinstitution of iNO within 24 h of weaning, and utilization of the pulmonary hypertension consult.

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Fischer, H., Singh, T., Devlin, L. et al. A quality improvement project improving the value of iNO utilization in preterm and term infants. J Perinatol (2020). https://doi.org/10.1038/s41372-020-0768-0

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