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

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
• 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
• 3 Lapointe A, Barrington KJ. Pulmonary hypertension and the asphyxiated newborn. J Pediatr 2011; 158 (2, Suppl): e19-e24
• 4 Lowson SM. Alternatives to nitric oxide. Br Med Bull 2004; 70 (03) 119-131
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 14 Rashid A, Ivy D. Severe paediatric pulmonary hypertension: new management strategies. Arch Dis Child 2005; 90 (01) 92-98
• 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
• 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
• 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
• 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
• 19 Lowson SM. Inhaled alternatives to nitric oxide. Anesthesiology 2002; 96 (06) 1504-1513
• 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