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Inhaled Iloprost as a First-Line Therapy for Persistent Pulmonary Hypertension of the Newborn

  • Kim, Seung Hyun (Department of Pediatrics, Hanyang University College of Medicine) ;
  • Lee, Hyun Ju (Department of Pediatrics, Hanyang University College of Medicine) ;
  • Kim, Nam Su (Department of Pediatrics, Hanyang University College of Medicine) ;
  • Park, Hyun-Kyung (Department of Pediatrics, Hanyang University College of Medicine)
  • 투고 : 2019.03.27
  • 심사 : 2019.10.15
  • 발행 : 2019.11.30

초록

Purpose: Persistent pulmonary hypertension of the newborn (PPHN) is a potentially fatal disease. Inhaled iloprost, a stable analogue of prostacyclin, has recently been used as a therapeutic option. However, there are no clinical guidelines on the use of iloprost, specifically for neonates. This study aimed to suggest the use of inhaled iloprost as a rescue therapy for PPHN based on our experience. Methods: The efficacy and adverse events of inhaled iloprost were evaluated prospectively in nine full-term neonates with PPHN. We monitored the following parameters: fraction of inspired oxygen (FiO2), respiratory severity score (RSS), heart rate, and mean blood pressure. Results: The inhalation dose was 1 to 2 ㎍/kg initially, and 4 to 8 inhalations per day were applied over 2 to 8 days, except in the case of one neonate who died 2 days after birth. Echocardiographic findings, changes in FiO2, and RSS improved within the next 7 days in eight of the nine patients. Severe side effects on heart rate and blood pressure were not observed. Conclusion: Our experience suggests that inhaled iloprost can be used as a first-line treatment in newborn infants with PPHN when inhaled nitric oxide is not available. To the best of our knowledge, this report is the first prospective case series on the use of inhaled iloprost in PPHN.

키워드

과제정보

This research was supported by the Korea Special Therapeutic Education Center (Chairman Il-Kewon Kim) of Anyang, Korea.

참고문헌

  1. Nair J, Lakshminrusimha S. Update on PPHN: mechanisms and treatment. Semin Perinatol 2014;38:78-91. https://doi.org/10.1053/j.semperi.2013.11.004
  2. Maxey DM, Ivy DD, Ogawa MT, Feinstein JA. Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients. Pediatr Cardiol 2013;34:1628-36. https://doi.org/10.1007/s00246-013-0688-2
  3. Ehlen M, Wiebe B. Iloprost in persistent pulmonary hypertension of the newborn. Cardiol Young 2003;13:361-3. https://doi.org/10.1017/S1047951103000726
  4. Avila-Alvarez A, Bravo-Laguna MC, Bronte LD, Del Cerro MJ. Inhaled iloprost as a rescue therapy for transposition of the great arteries with persistent pulmonary hypertension of the newborn. Pediatr Cardiol 2013;34:2027-9. https://doi.org/10.1007/s00246-012-0575-2
  5. De Luca D, Zecca E, Piastra M, Romagnoli C. Iloprost as 'rescue' therapy for pulmonary hypertension of the neonate. Paediatr Anaesth 2007;17:394-5. https://doi.org/10.1111/j.1460-9592.2006.02104.x
  6. Yilmaz O, Kahveci H, Zeybek C, Ciftel M, Kilic O. Inhaled iloprost in preterm infants with severe respiratory distress syndrome and pulmonary hypertension. Am J Perinatol 2014;31:321-6. https://doi.org/10.1055/s-0033-1348949
  7. Chotigeat U, Jaratwashirakul S. Inhaled iloprost for severe persistent pulmonary hypertension of the newborn. J Med Assoc Thai 2007;90:167-70.
  8. Limsuwan A, Wanitkul S, Khosithset A, Attanavanich S, Samankatiwat P. Aerosolized iloprost for postoperative pulmonary hypertensive crisis in children with congenital heart disease. Int J Cardiol 2008;129:333-8. https://doi.org/10.1016/j.ijcard.2007.08.084
  9. Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev 2007;3:CD005494.
  10. Dhillon R. The management of neonatal pulmonary hypertension. Arch Dis Child Fetal Neonatal Ed 2012;97:F223-8. https://doi.org/10.1136/adc.2009.180091
  11. Kirbas A, Yalcin Y, Tanrikulu N, Gurer O, Isik O. Comparison of inhaled nitric oxide and aerosolized iloprost in pulmonary hypertension in children with congenital heart surgery. Cardiol J 2012;19:387-94. https://doi.org/10.5603/CJ.2012.0070
  12. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest 2007;131:1917-28. https://doi.org/10.1378/chest.06-2674
  13. Piastra M, De Luca D, De Carolis MP, Tempera A, Stival E, Caliandro F, et al. Nebulized iloprost and noninvasive respiratory support for impending hypoxaemic respiratory failure in formerly preterm infants: a case series. Pediatr Pulmonol 2012;47:757-62. https://doi.org/10.1002/ppul.21619
  14. Eifinger F, Sreeram N, Mehler K, Huenseler C, Kribs A, Roth B. Aerosolized iloprost in the treatment of pulmonary hypertension in extremely preterm infants: a pilot study. Klin Padiatr 2008;220:66-9. https://doi.org/10.1055/s-2007-984370
  15. Hwang SK, O YC, Kim NS, Park HK, Yum MK. Use of inhaled iloprost in an infant with bronchopulmonary dysplasia and pulmonary artery hypertension. Korean Circ J 2009;39:343-5. https://doi.org/10.4070/kcj.2009.39.8.343
  16. Gurakan B, Kayiran P, Ozturk N, Kayiran SM, Dindar A. Therapeutic combination of sildenafil and iloprost in a preterm neonate with pulmonary hypertension. Pediatr Pulmonol 2011;46:617-20. https://doi.org/10.1002/ppul.21415
  17. Mohamed WA, Ismail M. A randomized, double-blind, placebocontrolled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol 2012;32:608-13. https://doi.org/10.1038/jp.2011.157
  18. Kahveci H, Yilmaz O, Avsar UZ, Ciftel M, Kilic O, Laloglu F, et al. Oral sildenafil and inhaled iloprost in the treatment of pulmonary hypertension of the newborn. Pediatr Pulmonol 2014; 49:1205-13. https://doi.org/10.1002/ppul.22985
  19. Majed BH, Khalil RA. Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn. Pharmacol Rev 2012;64:540-82. https://doi.org/10.1124/pr.111.004770
  20. Han YK, Lee SM, Eun HS, Kim JE, Namgung R, Park MS, et al. The therapeutic effect of inhaled iloprost in newborn infants with severe persistent pulmonary hypertension refractory to inhaled nitric oxide. Korean J Perinatol 2011;22:57-63.
  21. Mulligan C, Beghetti M. Inhaled iloprost for the control of acute pulmonary hypertension in children: a systematic review. Pediatr Crit Care Med 2012;13:472-80. https://doi.org/10.1097/PCC.0b013e31822f192b
  22. Eronen M, Pohjavuori M, Andersson S, Pesonen E, Raivio KO. Prostacyclin treatment for persistent pulmonary hypertension of the newborn. Pediatr Cardiol 1997;18:3-7. https://doi.org/10.1007/s002469900099