Skip to main content
SpringerLink
Log in

Mise au point sur les traitements de l’hypertension artérielle pulmonaire de l’enfant

Update on targeted therapies in pediatric pulmonary arterial hypertension

  • Enseignement Supérieur en Réanimation Pédiatrique
  • Published:
Réanimation

Résumé

Le traitement de l’hypertension artérielle pulmonaire (HTAP) de l’enfant a été révolutionné par l’avènement de traitements oraux spécifiques. Ces traitements sont indiqués exclusivement dans l’HTAP, à distinguer des autres situations cliniques responsables d’hypertension pulmonaire, particulièrement en réanimation. Il n’y a pas de données pédiatriques prouvant que ces nouvelles drogues sont utiles et sûres en dehors des HTAP. En particulier, il n’y a pas aujourd’hui d’information sur l’utilisation de ces drogues spécifiques dans l’HTAP persistante du nouveau-né ou dans la période postopératoire de chirurgie cardiaque. Le traitement des HTAP associées aux cardiopathies congénitales est un des problèmes actuellement difficiles à approcher. C’est également celui où les espoirs sont les plus grands. Les antagonistes des récepteurs à l’endothéline et les inhibiteurs de la phosphodiestérase de type 5 (PDE-5) ont reçu une autorisation pédiatrique. Les thérapeutiques les plus utilisées en réanimation sont les analogues de la prostacycline, disponibles uniquement par voie parentérale, la voie intraveineuse étant la plus adaptée. Ces différentes drogues peuvent être utilisées seules ou en combinaison, instaurées de façon séquentielle ou d’emblée. De nombreux essais thérapeutiques sont en cours chez l’adulte et l’enfant et laissent présager des progrès prochains. Les traitements non médicamenteux ont une place importante: l’atrioseptotomie, l’anastomose de Potts ainsi que la transplantation pulmonaire sont indiquées quand le traitement médical maximal ne suffit plus.

Abstract

Treatment of pediatric pulmonary arterial hypertension (PAH) has dramatically changed with the recent availability of specific oral drugs. These new treatments have been exclusively approved in PAH that should be differentiated from other causes of pulmonary hypertension particularly frequent in intensive care unit (ICU) patients. In pediatrics, data assessing efficacy and safety of these drugs do not exist in other settings than PAH. Consistently, these drugs are not recommended in persistent pulmonary hypertension of the newborn or during the postoperative course of cardiac surgery, even if routinely used. Treatment of PAH associated with congenital heart diseases represents a major concern and designing trials is challenging due to the possible benefits for children. Endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors have been approved in Europe for children use. Prostanoids including epoprostenol are largely used in the ICU, mostly by intravenous route. Specific PAH drugs may be used alone or in combination. Several trials are ongoing to test the best combination strategy with preliminary hopeful results suggesting significant improvement for the future. Creation of right-to-left shunts (atrioseptotomy and Potts’ anastomosis) as well as lung transplantation should be indicated when children’s clinical situation worsen despite optimal PAH pharmacological management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Références

  1. Galiè N, Hoeper MM, Humbert M, et al (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30:2493–2537

    Article  PubMed  Google Scholar 

  2. Humbert M, Sitbon O, Chaouat A, et al (2006) Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 173:1023–1030

    Article  PubMed  Google Scholar 

  3. Galiè N, Rubin Lj, Hoeper M, et al (2008) Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 371:2093–2100

    Article  PubMed  Google Scholar 

  4. Haworth SG, Hislop AA (2009) Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001–2006. Heart 95:312–317

    Article  PubMed  CAS  Google Scholar 

  5. Berger RM. (2009) Pulmonary hypertension associated with congenital cardiac disease. Cardiol Young 29:1–4

    Google Scholar 

  6. Lévy M, Maurey C, Celermajer DS, et al (2007) Impaired apoptosis of pulmonary endothelial cells is associated with intimal proliferation and irreversibility of pulmonary hypertension in congenital heart disease. J Am Coll Cardiol 49:803–810

    Article  PubMed  Google Scholar 

  7. Palma G, Giodarno R, Russolillo V, et al (2011) Sildenafil therapy for pulmonary hypertension before and after pediatric congenital heart surgery. Tex Heart Inst J 38:238–242

    PubMed  Google Scholar 

  8. Nemoto S, Sasaki T, Ozawa H, et al (2010) Oral sildenafil for persistent pulmonary hypertension early ater congenital cardiac surgery in children. Eur J Cardiothorac Surg 38:71–77

    Article  PubMed  Google Scholar 

  9. Fraisse A, Butrous G, Taylor MB, et al (2011) Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease. Intensie Care Med 37:502–509

    Article  CAS  Google Scholar 

  10. Widlitz A, Barst RJ (2003) Pulmonary arterial hypertension in children. Eur Respir J 21:155–176

    Article  PubMed  CAS  Google Scholar 

  11. Sitbon O, Humbert M, Jaïs X, et al (2005) Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 111:3105–3111

    Article  PubMed  CAS  Google Scholar 

  12. Barst RJ, Ivy D, Dingemanse J, et al (2003) Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther 73:372–382

    Article  PubMed  CAS  Google Scholar 

  13. Beghetti M, Haworth SG, Bonnet D, et al (2009) Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study. Br J Clin Pharmacol 68:948–955

    Article  PubMed  CAS  Google Scholar 

  14. Sandoval J, Bauerle O, Gomez A, et al (1995) Primary pulmonary hypertension in children: clinical characterization and survival. J Am Coll Cardiol 25:466–474

    Article  PubMed  CAS  Google Scholar 

  15. Beghetti M, Hoeper MM, Kiely DG, et al (2008) Safety experience with bosentan in 146 children 2–11 years old with pulmonary arterial hypertension: results from the European Postmarketing Surveillance program. Pediatr Res 64:200–204

    Article  PubMed  CAS  Google Scholar 

  16. Rosenzweig EB, Ivy DD, Widlitz A, et al (2005) Effects of longterm bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 46:697–704

    Article  PubMed  CAS  Google Scholar 

  17. Barst RJ, Ivy DD, Gaitan G, et al (2012) A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation 125:324–334

    Article  PubMed  CAS  Google Scholar 

  18. Simonneau G, Rubin LJ, Galiè N, et al PACES Study Group (2008) Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med 149:521–530

    PubMed  Google Scholar 

  19. Takatsuki S, Calderbank M, Ivy DD (2012) Initial experience with tadalafil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 33:683–688

    Article  PubMed  Google Scholar 

  20. McLaughlin VV, Badesch DB, Delcroix M, et al (2009) End points and clinical trial design in pulmonary arterial hypertension. J Am Coll Cardiol 54(1 Suppl):S97–S107

    Article  PubMed  Google Scholar 

  21. Barst RJ, Maislin G, Fishman AP. (1999) Vasodilator therapy for primary pulmonary hypertension in children. Circulation 99:1197–1208

    Article  PubMed  CAS  Google Scholar 

  22. Dickinson MG, Schölvinck EH, Boonstra A, et al (2009) Low complication rates with totally implantable access port use in epoprostenol treatment of pulmonary hypertension. J Heart Lung Transplant 28:273–279

    Article  PubMed  Google Scholar 

  23. Ivy DD, Doran AK, Smith KJ, et al (2008) Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J Am Coll Cardiol 51:161–169

    Article  PubMed  CAS  Google Scholar 

  24. Levy M, Celermajer DS, Bourges-Petit E, et al (2011) Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr 158:584–588

    Article  PubMed  Google Scholar 

  25. Micheletti A, Hislop AA, Lammers A, et al (2006) Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart 92:969–972

    Article  PubMed  CAS  Google Scholar 

  26. Baruteau AE, Serraf A, Lévy M, et al (2012) Potts’ shunt in children with idiopathic pulmonary arterial hypertension: long-term results. Ann Thorac Surg 94:817–824

    Article  PubMed  Google Scholar 

  27. Berger RM, Beghetti M, Humpl T, et al (2012) Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 379:537–546

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de référence malformations cardiaques congénitales complexes-M3C, Université Paris Descartes, hôpital Necker-Enfants Malades, 149, rue de Sèvres, F-75015, Paris, France

    D. Bonnet, M. Lévy & F. Bajolle

Authors
  1. D. Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Lévy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Bajolle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Bonnet.

Additional information

Cet article correspond à la conférence faite par l’auteur au congrès de la SRLF 2013 dans la session: Hypertension pulmonaire de l’enfant.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bonnet, D., Lévy, M. & Bajolle, F. Mise au point sur les traitements de l’hypertension artérielle pulmonaire de l’enfant. Réanimation 22 (Suppl 2), 359–364 (2013). https://doi.org/10.1007/s13546-012-0637-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13546-012-0637-8

Mots clés

Keywords

Search

Navigation