Download PDF
Am J Perinatol 2019; 36(11): 1142-1149
DOI: 10.1055/s-0038-1676483
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhaled Epoprostenol for Pulmonary Hypertension Treatment in Neonates: A 12-Year Experience

Frédérique Berger-Caron
1   Department of Paediatrics, CHU de Québec, Université Laval, Québec City, Québec, Canada
,
Bruno Piedboeuf
2   Division of Neonatology, Department of Paediatrics, CHU de Québec, Université Laval, Québec City, Québec, Canada
,
Geneviève Morissette
3   Division of Pediatric Intensive Care, Department of Paediatrics, CHU de Québec, Université Laval, Québec City, Québec, Canada
,
David Simonyan
4   Department of Biostatistic, Centre de recherche du CHUQ, Université Laval, Québec City, Québec, Canada
,
Philippe Chétaille
5   Division of Pediatric Cardiology, Department of Paediatrics, CHU de Québec, Québec City, Québec, Canada
,
Annie Pellerin
6   Department of Pharmacy, CHU de Québec, Université Laval, Québec City, Québec, Canada
,
Audrey Hébert
2   Division of Neonatology, Department of Paediatrics, CHU de Québec, Université Laval, Québec City, Québec, Canada
› Author Affiliations
Further Information

Publication History

31 July 2018

19 October 2018

Publication Date:
14 December 2018 (online)

   Permissions and Reprints

Abstract

Background Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI2) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use.

Objectives The primary objective was to evaluate the efficacy of iPGI2 for PPHN. The secondary objectives were to describe its use in neonates and assess side effects.

Study Design This retrospective cohort study included infants < 28 days with PPHN treated with iPGI2 in the neonatal or pediatric intensive care units of our institution between 2004 and 2016.

Results We reviewed 43 patient' care episodes (mean gestational age of 36 weeks). This was an extremely ill population with 54% mortality rate. Oxygenation index improved significantly after 12-hour treatment (p = 0.047), with a rebound effect when discontinuing nebulization. By the end of the therapy, the fraction of inspired oxygen had significantly dropped (p = 0.0018). Echocardiographic markers tended to normalize during treatment. No potential side effects were reported.

Conclusion In these sick newborns, we observed an improvement in PPHN under iPGI2 without significant adverse effects. To our knowledge, this is the largest neonatal cohort reported to have received iPGI2 for PPHN.

Keywords

pulmonary hypertension - neonate - inhaled epoprostenol - inhaled prostacyclin - persistent pulmonary hypertension of the newborn - oxygenation index
 

  • References

  • 1 Steinhorn RH. Neonatal pulmonary hypertension. Pediatr Crit Care Med 2010; 11 (2, Suppl): S79-S84
    CrossrefPubMedGoogle Scholar
  • 2 Sood BG, Delaney-Black V, Aranda JV, Shankaran S. Aerosolized PGE1: a selective pulmonary vasodilator in neonatal hypoxemic respiratory failure results of a Phase I/II open label clinical trial. Pediatr Res 2004; 56 (04) 579-585
    CrossrefPubMedGoogle Scholar
  • 3 Lapointe A, Barrington KJ. Pulmonary hypertension and the asphyxiated newborn. J Pediatr 2011; 158 (2, Suppl): e19-e24
    CrossrefPubMedGoogle Scholar
  • 4 Lowson SM. Alternatives to nitric oxide. Br Med Bull 2004; 70 (03) 119-131
    CrossrefPubMedGoogle Scholar
  • 5 Jain A, McNamara PJ. Persistent pulmonary hypertension of the newborn: advances in diagnosis and treatment. Semin Fetal Neonatal Med 2015; 20 (04) 262-271
    CrossrefPubMedGoogle Scholar
  • 6 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 (01) CD000399
    PubMedGoogle Scholar
  • 7 Kelly LK, Porta NFM, Goodman DM, Carroll CL, Steinhorn RH. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J Pediatr 2002; 141 (06) 830-832
    CrossrefPubMedGoogle Scholar
  • 8 De Luca D, Cogo P, Zecca E. , et al. Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review. Eur Respir J 2011; 37 (03) 678-689
    CrossrefPubMedGoogle Scholar
  • 9 Barst RJ, Rubin LJ, Long WA. , et al; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996; 334 (05) 296-301
    CrossrefPubMedGoogle Scholar
  • 10 Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121 (06) 409-415
    PubMedGoogle Scholar
  • 11 Soditt V, Aring C, Groneck P. Improvement of oxygenation induced by aerosolized prostacyclin in a preterm infant with persistent pulmonary hypertension of the newborn. Intensive Care Med 1997; 23 (12) 1275-1278
    CrossrefPubMedGoogle Scholar
  • 12 De Jaegere AP, van den Anker JN. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. Eur Respir J 1998; 12 (04) 932-934
    CrossrefPubMedGoogle Scholar
  • 13 Rimensberger PC, Spahr-Schopfer I, Berner M. , et al. Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms. Circulation 2001; 103 (04) 544-548
    CrossrefPubMedGoogle Scholar
  • 14 Rashid A, Ivy D. Severe paediatric pulmonary hypertension: new management strategies. Arch Dis Child 2005; 90 (01) 92-98
    CrossrefPubMedGoogle Scholar
  • 15 Dahlem P, van Aalderen WM, de Neef M, Dijkgraaf MG, Bos AP. Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury. Crit Care Med 2004; 32 (04) 1055-1060
    CrossrefPubMedGoogle Scholar
  • 16 Bindl L, Fahnenstich H, Peukert U. Aerosolised prostacyclin for pulmonary hypertension in neonates. Arch Dis Child Fetal Neonatal Ed 1994; 71 (03) F214-F216
    CrossrefPubMedGoogle Scholar
  • 17 Zwissler B, Rank N, Jaenicke U. , et al. Selective pulmonary vasodilation by inhaled prostacyclin in a newborn with congenital heart disease and cardiopulmonary bypass. Anesthesiology 1995; 82 (06) 1512-1516
    CrossrefPubMedGoogle Scholar
  • 18 Brown AT, Gillespie JV, Miquel-Verges F. , et al. Inhaled epoprostenol therapy for pulmonary hypertension: Improves oxygenation index more consistently in neonates than in older children. Pulm Circ 2012; 2 (01) 61-66
    CrossrefPubMedGoogle Scholar
  • 19 Lowson SM. Inhaled alternatives to nitric oxide. Anesthesiology 2002; 96 (06) 1504-1513
    CrossrefPubMedGoogle Scholar
  • 20 De Luca D, Zecca E, Piastra M, Romagnoli C. Iloprost as ‘rescue’ therapy for pulmonary hypertension of the neonate. Paediatr Anaesth 2007; 17 (04) 394-395
    CrossrefPubMedGoogle Scholar