European Journal of Pediatrics

, Volume 164, Issue 10, pp 626–629 | Cite as

Severe persistent pulmonary hypertension of the newborn in a setting where limited resources exclude the use of inhaled nitric oxide: successful treatment with sildenafil

  • Amadu E. JulianaEmail author
  • Filomena C. B. Abbad
Original Paper


We present the case of a full term neonate with severe persistent pulmonary hypertension of the newborn (PPHN) after birth asphyxia cared for at the St. Elizabeth Hospital in Curacao, Netherlands Antilles. Although the child was ventilated with high pressures and was given high doses of cardiovascular pressors, the arterial oxygen levels remained low with an alveolar-arterial O2 gradient of 651 mmHg. As a last resort, sildenafil (1.5 mg/kg) was given via a nasogastric tube. This resulted in an immediate and sustained elevation of arterial oxygenation and subsequent complete recovery. After administration of sildenafil there was a transient hypotension which was corrected by a single bolus of saline. Conclusion:We discuss the current treatment modalities of persistent pulmonary hypertension of the newborn and the potential use of phosphodiesterase 5 inhibitors such as sildenafil in a situation where the standard of practice with inhaled nitric oxide and extracorporeal membrane oxygenation is not available.


Persistent pulmonary hypertension of the newborn Sildenafil 



extracorporeal membrane oxygenation


inhaled nitric oxide




persistent pulmonary hypertension of the newborn



We wish to thank Prof. R. M. F. Berger (Beatrix Children’s Hospital/University Hospital, Groningen, The Netherlands) and Prof. Rashmin C. Savani (Children’s Hospital of Philadelphia, USA) for their advice and critical review of the article.


  1. 1.
    American Academy of Pediatrics. Committee on Fetus and Newborn (2000) Use of inhaled nitric oxide. Pediatrics 106: 344–345CrossRefPubMedGoogle Scholar
  2. 2.
    Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ, Weir EK (1994) Nitric oxide and c-GMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by c-GMP-dependent protein kinase. Proc Natl Acad Sci U S A 9116: 7583–7587Google Scholar
  3. 3.
    Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, Roy BJ, Keszler M, Kinsella JP (2000) Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med 342: 469–474CrossRefPubMedGoogle Scholar
  4. 4.
    Clark RH, Huckaby JL, Kueser TJ, Walker MW, Southgate WM, Perez JA, Roy BJ, Keszler M (2003) Low-dose nitric oxide therapy for persistent pulmonary hypertension: 1-year follow-up. J Perinatol 23: 300–303CrossRefPubMedGoogle Scholar
  5. 5.
    Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang CT (1998) 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. Pediatrics101: 325–334Google Scholar
  6. 6.
    Finer NN, Barrington KJ (2001) Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 4: CD000399PubMedGoogle Scholar
  7. 7.
    Inhaled Nitric Oxide in Full-Term and Nearly Full-Term Infants With Hypoxic Respiratory Failure. The Neonatal Inhaled Nitric Oxide Study Group (1997). N Engl J Med 336: 597–604CrossRefPubMedGoogle Scholar
  8. 8.
    Ichinose F, Adrie C, Hurford WE, Bloch KD, Zapol WM (2001) Selective pulmonary vasodilation induced by aerosolized zaprinast. Anesthesiology 88: 410–416Google Scholar
  9. 9.
    Ichinose F, Erana-Garcia J, Hromi J, Raveh Y, Jones R, Krim L, Clark MW, Winkler JD, Bloch KD, Zapol WM (2001) Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Crit Care Med 29: 1000–1005CrossRefPubMedGoogle Scholar
  10. 10.
    Kinsella JP, Truog WE, Walsh WF, Goldberg RN, Bancalari E, Mayock DE, Redding GJ, deLemos RA, Sardesai S, McCurnin DC, Moreland SG, Cutter GR, Abman SH (1997) Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn. J Pediatr 131: 55–62PubMedGoogle Scholar
  11. 11.
    Karatza AA, Bush A, Magee AG (2002) Images in congenital heart disease. Reversal of shunting in pulmonary hypertension after treatment with oral sildenafil. Cardiol Young 12: 561–562Google Scholar
  12. 12.
    Perry MJ, Higgs GA (1998) Chemotherapeutic potential of phosphodiesterase Inhibitors. Curr Opin Chem Biol 2: 472–481Google Scholar
  13. 13.
    Roberts JD Jr, Fineman JR, Morin FC III, Shaul PW, Rimar S, Schreiber MD, Polin RA, Zwass MS, Zayek MM, Gross I, Heymann MA, Zapol WM (1997) Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med 336: 605–610CrossRefPubMedGoogle Scholar
  14. 14.
    Shekerdemian LS, Ravn HB, Penny DJ (2002) Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med 165: 1098–1102Google Scholar
  15. 15.
    Symeonides S, Balk RA (1999) Nitric oxide in the pathogenesis of sepsis. Infect Dis Clin North Am 13: 449–463CrossRefPubMedGoogle Scholar
  16. 16.
    Travadi JN, Patole SK (2003) Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review. Pediatr Pulmonol 36: 529–535CrossRefPubMedGoogle Scholar
  17. 17.
    Wallis RM, Corbin JD, Francis SH, Ellis P (1999) Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 83: 3C–12CCrossRefPubMedGoogle Scholar
  18. 18.
    Walsh-Sukys MC, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, Verter J, Stoll BJ, Lemons JA, Papile LA, Shankaran S, Donovan EF, Oh W, Ehrenkranz RA, Fanaroff AA (2000) Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 105: 14–20CrossRefPubMedGoogle Scholar
  19. 19.
    Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, Zapol WM (2000) Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology 92: 1702–1712CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Delfzicht ZiekenhuisDelfzijl The Netherlands
  2. 2.St. Elizabeth HospitalWillemstad Curacao, Netherlands Antilles

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