Download PDF
Am J Perinatol 2014; 31(04): 321-326
DOI: 10.1055/s-0033-1348949
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhaled Iloprost in Preterm Infants with Severe Respiratory Distress Syndrome and Pulmonary Hypertension

Osman Yilmaz
1   Department of Pediatric Cardiology, District Training and Research Hospital, Erzurum, Turkey
,
Hasan Kahveci
2   Department of Neonatal Intensive Care Unit, Nenehatun Obstetrics and Gynecology Hospital, Erzurum, Turkey
,
Cenap Zeybek
1   Department of Pediatric Cardiology, District Training and Research Hospital, Erzurum, Turkey
,
Murat Ciftel
1   Department of Pediatric Cardiology, District Training and Research Hospital, Erzurum, Turkey
,
Omer Kilic
3   Department of Pediatric Infectious Diseases, District Training and Research Hospital, Erzurum, Turkey
› Author Affiliations
Further Information

Publication History

28 February 2013

16 May 2013

Publication Date:
24 June 2013 (online)

    Permissions and Reprints

Abstract

Objective Many vasodilator drugs, including inhaled iloprost, are used to treat insufficient pulmonary vasodilatation, which is the main issue in pulmonary hypertension in newborns.

Study Design The safety and efficacy of inhaled iloprost for the treatment of pulmonary hypertension were evaluated retrospectively in 15 preterm infants diagnosed with respiratory distress syndrome and pulmonary hypertension.

Results The infants were unresponsive to surfactant and conventional mechanical ventilation and thus were treated with inhaled iloprost. Oxygenation parameters and hypoxemia improved rapidly after treatment. There was no decline in systemic blood pressure, no need for increased doses of vasopressor, and no side effects during treatment. One patient died of sepsis during treatment.

Conclusion In the treatment of severely sick premature babies with pulmonary hypertension, inhaled iloprost has high tolerability and a low incidence of systemic side effects. Based on the benefits of inhaled iloprost in preterm infants with pulmonary hypertension in this case series, further studies are required to evaluate its efficacy and safety in the preterm population.

Keywords

pulmonary hypertension - nitric oxide - aerosolized iloprost - preterm infant
 

  • References

  • 1 Rudolph AM. Fetal and neonatal pulmonary circulation. Annu Rev Physiol 1979; 41: 383-395
    CrossrefPubMedGoogle Scholar
  • 2 Whitsett JA, Pryhuber GS, Rice WR , et al. Acute respiratory disorders. In: Avery GB, Fletcher MA, Macdonald MG, , eds. Neonatology: Pathophysiology and Management of the Newborn. 5th ed. Baltimore, MD: Lippincott Williams and Wilkins; 1999: 497-501
    Google Scholar
  • 3 Walther FJ, Benders MJ, Leighton JO. Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome. Pediatrics 1992; 90: 899-904
    PubMedGoogle Scholar
  • 4 Yeh TF. Persistent pulmonary hypertension in preterm infants with respiratory distress syndrome. Pediatr Pulmonol 2001; (Suppl. 23) 103-106
    PubMedGoogle Scholar
  • 5 Ostrea EM, Villanueva-Uy ET, Natarajan G, Uy HG. Persistent pulmonary hypertension of the newborn: pathogenesis, etiology, and management. Paediatr Drugs 2006; 8: 179-188
    CrossrefPubMedGoogle Scholar
  • 6 Skinner JR, Boys RJ, Hunter S, Hey EN. Pulmonary and systemic arterial pressure in hyaline membrane disease. Arch Dis Child 1992; 67 (Spec No): 366-373
    CrossrefPubMedGoogle Scholar
  • 7 De Jaegere AP, van den Anker JN. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. Eur Respir J 1998; 12: 932-934
    CrossrefPubMedGoogle Scholar
  • 8 Dhillon R. The management of neonatal pulmonary hypertension. Arch Dis Child Fetal Neonatal Ed 2012; 97: F223-F228
    CrossrefPubMedGoogle Scholar
  • 9 Ehlen M, Wiebe B. Iloprost in persistent pulmonary hypertension of the newborn. Cardiol Young 2003; 13: 361-363
    Google Scholar
  • 10 Roberts Jr JD, Fineman JR, Morin III FC , et al; The Inhaled Nitric Oxide Study Group. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. N Engl J Med 1997; 336: 605-610
    CrossrefPubMedGoogle Scholar
  • 11 Walsh-Sukys MC, Tyson JE, Wright LL , et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 2000; 105 (1 Pt 1) 14-20
    CrossrefPubMedGoogle Scholar
  • 12 Van Meurs KP, Wright LL, Ehrenkranz RA , et al; Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 2005; 353: 13-22
    CrossrefPubMedGoogle Scholar
  • 13 Cole FS, Alleyne C, Barks JD , et al. NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants. Pediatrics 2011; 127: 363-369
    CrossrefPubMedGoogle Scholar
  • 14 Bindl L, Fahnenstich H, Peukert U. Aerosolised prostacyclin for pulmonary hypertension in neonates. Arch Dis Child Fetal Neonatal Ed 1994; 71: F214-F216
    CrossrefPubMedGoogle Scholar
  • 15 Kelly LK, Porta NF, Goodman DM, Carroll CL, Steinhorn RH. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J Pediatr 2002; 141: 830-832
    CrossrefPubMedGoogle Scholar
  • 16 Lakshminrusimha S, Porta NF, Farrow KN , et al. Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med 2009; 10: 106-112
    CrossrefPubMedGoogle Scholar
  • 17 Krause W, Krais T. Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man. Eur J Clin Pharmacol 1986; 30: 61-68
    CrossrefPubMedGoogle Scholar
  • 18 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: 66-69
    Google Scholar
  • 19 Golan A, Zalzstein E, Zmora E, Shinwell ES. Pulmonary hypertension in respiratory distress syndrome. Pediatr Pulmonol 1995; 19: 221-225
    CrossrefPubMedGoogle Scholar
  • 20 Tolsa JF, Cotting J, Sekarski N, Payot M, Micheli JL, Calame A. Magnesium sulphate as an alternative and safe treatment for severe persistent pulmonary hypertension of the newborn. Arch Dis Child Fetal Neonatal Ed 1995; 72: F184-F187
    CrossrefPubMedGoogle Scholar
  • 21 Abu-Osba YK, Galal O, Manasra K, Rejjal A. Treatment of severe persistent pulmonary hypertension of the newborn with magnesium sulphate. Arch Dis Child 1992; 67 (1 Spec No) 31-35
    CrossrefPubMedGoogle Scholar
  • 22 Boo NY, Rohana J, Yong SC, Bilkis AZ, Yong-Junina F. Inhaled nitric oxide and intravenous magnesium sulphate for the treatment of persistent pulmonary hypertension of the newborn. Singapore Med J 2010; 51: 144-150
    PubMedGoogle Scholar
  • 23 Lipsitz PJ. The clinical and biochemical effects of excess magnesium in the newborn. Pediatrics 1971; 47: 501-509
    PubMedGoogle Scholar
  • 24 Barrington KJ, Finer NN. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev 2001; (4) CD000509
    PubMedGoogle Scholar
  • 25 Kumar VH, Hutchison AA, Lakshminrusimha S, Morin III FC, Wynn RJ, Ryan RM. Characteristics of pulmonary hypertension in preterm neonates. J Perinatol 2007; 27: 214-219
    CrossrefPubMedGoogle Scholar
  • 26 Stolar CJ, Snedecor SM, Bartlett RH. Extracorporeal membrane oxygenation and neonatal respiratory failure: experience from the extracorporeal life support organization. J Pediatr Surg 1991; 26: 563-571
    CrossrefPubMedGoogle Scholar
  • 27 Mulligan C, Beghetti M. Inhaled iloprost for the control of acute pulmonary hypertension in children: a systematic review. Pediatr Crit Care Med 2012; 13: 472-480
    CrossrefPubMedGoogle Scholar
  • 28 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: 1275-1278
    CrossrefPubMedGoogle Scholar
  • 29 Piastra M, De Luca D, De Carolis MP , et al. Nebulized iloprost and noninvasive respiratory support for impending hypoxaemic respiratory failure in formerly preterm infants: a case series. Pediatr Pulmonol 2012; 47: 757-762
    Google Scholar
  • 30 Gürakan B, Kayiran P, Oztürk N, Kayiran SM, Dindar A. Therapeutic combination of sildenafil and iloprost in a preterm neonate with pulmonary hypertension. Pediatr Pulmonol 2011; 46: 617-620
    CrossrefPubMedGoogle Scholar
  • 31 Tissot C, Beghetti M. Review of inhaled iloprost for the control of pulmonary artery hypertension in children. Vasc Health Risk Manag 2009; 5: 325-331
    PubMedGoogle Scholar