Neonatal Medicine

The Korean Society of Neonatology (대한신생아학회)
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Clinical Status of Inhaled Nitric Oxide Treatment in Infants with Persistent Pulmonary Hypertension of the Newborn in Korea: Post-Marketing Surveillance Results

  • Ha, Jaewook (Department of Pediatrics, Korea University College of Medicine) ;
  • Lee, Eun Hee (Department of Pediatrics, Korea University College of Medicine) ;
  • Park, Hyun-Kyung (Department of Pediatrics, Hanyang University College of Medicine) ;
  • Choi, Byung Min (Department of Pediatrics, Korea University College of Medicine)
  • Received : 2019.09.14
  • Accepted : 2019.12.12
  • Published : 2020.05.31
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Abstract

Purpose: Inhaled nitric oxide (iNO) is a potent selective pulmonary vasodilator and an important treatment for newborn infants with hypoxic respiratory failure due to persistent pulmonary hypertension of the newborn (PPHN). The Ministry of Food and Drug Safety of Korea first approved iNO in 2009 for use as a new drug to treat hypoxic respiratory failure with PPHN. A post-marketing surveillance study (PMSS) was conducted to assess the effectiveness and safety of the iNO treatment. We evaluated the clinical status of the iNO treatment currently available in Korea by using the PMSS data. Methods: We retrospectively reviewed the PMSS data from 22 hospitals in Korea from October 2014 to September 2018. Altogether, 97 infants were enrolled and divided into early response (ER), delayed response (DR), no response (NR), and death groups according to their response to the iNO treatment. Results: The ER group included 52 infants (53.6%); DR group, 33 (34.0%); NR group, seven (7.2%); and death group, five (5.2%). The iNO treatment was initiated within 14 days after birth at a concentration of 20 ppm. The median treatment duration was 91.5 hours (69.0 to 134.3) in all the infants. Of the infants, 43 (44.3%) received the treatment for >96 hours. Fifty-one infants (52.6%) needed >20 ppm of iNO, and 10 (10.5%) needed a maximum of 80 ppm of iNO. None of the infants had hypermethemoglobinemia or an alarm report of NO2. Conclusion: Korean neonatologists reported that a large proportion of the infants with PPHN showed improvement in oxygenation after treatment with the approved iNO. These infants received relatively longer durations and higher concentrations of the iNO treatment than the current recommendations, without any side and adverse effect.

Keywords

Acknowledgement

In this study, we used data collected from the post-marketing surveillance of INOmax inhalation drugs from Synex Consulting Ltd. We greatly appreciate pediatricians at 22 hospitals in Korea for thier sincere participation in the post-marketing surveillance and we also thanks Professor Ji Min Sung of Yonsei University for his support in statistical analysis.

References

  1. Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT, Stone D, Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991;338:1173-4. https://doi.org/10.1016/0140-6736(91)92033-X
  2. Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818-9. https://doi.org/10.1016/0140-6736(92)92686-A
  3. Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:819-20. https://doi.org/10.1016/0140-6736(92)92687-B
  4. Kinsella JP. Inhaled nitric oxide in the term newborn. Early Hum Dev 2008;84:709-16. https://doi.org/10.1016/j.earlhumdev.2008.08.002
  5. DiBlasi RM, Myers TR, Hess DR. Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure. Respir Care 2010;55:1717-45.
  6. Peliowski A; Canadian Paediatric Society, Fetus and Newborn Committee. Inhaled nitric oxide use in newborns. Paediatr Child Health 2012;17:95-100. https://doi.org/10.1093/pch/17.2.95
  7. Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997;336:597-604. https://doi.org/10.1056/NEJM199702273360901
  8. Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med 2000;342:469-74. https://doi.org/10.1056/NEJM200002173420704
  9. 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.
  10. Lee EH, Choi BM. Clinical application of inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn. Neonatal Med 2015;22:61-70. https://doi.org/10.5385/nm.2015.22.2.61
  11. Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, et al. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics 1998;101(3 Pt 1):325-34. https://doi.org/10.1542/peds.101.3.325
  12. Rhine WD, Suzuki S, Potenziano JL, Escalante S, Togari H. An analysis of time to improvement in oxygenation in Japanese preterm and late preterm or term neonates with hypoxic respiratory failure and pulmonary hypertension. Clin Ther 2019;41:910-9. https://doi.org/10.1016/j.clinthera.2019.03.008
  13. Goldman AP, Tasker RC, Haworth SG, Sigston PE, Macrae DJ. Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 1996;98(4 Pt 1):706-13.
  14. Guthrie SO, Walsh WF, Auten K, Clark RH. Initial dosing of inhaled nitric oxide in infants with hypoxic respiratory failure. J Perinatol 2004;24:290-4. https://doi.org/10.1038/sj.jp.7211087
  15. Ahn SY. Prognosis and side effects of inhaled nitric oxide treatment in persistent pulmonary hypertension of the newborn. Neonatal Med 2015;22:71-7. https://doi.org/10.5385/nm.2015.22.2.71

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