Download PDF
Intensivmedizin up2date 2006; 2(2): 177-193
DOI: 10.1055/s-2006-925309
Pädiatrische Intensivmedizin
© Georg Thieme Verlag KG Stuttgart · New York

Pulmonale Hypertonie im Kindesalter

Dietmar  Schranz
Further Information

Publication History

Publication Date:
05 July 2006 (online)

Also available at
    Permissions and Reprints All articles of this category

Kernaussagen

Die pulmonale Hypertonie wurde - basierend auf pathophysiologischen Prozessen an den Lungengefäßen, die allen Formen gemeinsam sind - durch eine WHO-Konferenz 2003 neu klassifiziert.

Die Diagnosestellung basiert auf den molekularen Mechanismen, die der Pathophysiologie der IPAH sowie den sekundären pulmonalen Hypertonien bei angeborenen Herzfehlern und bei alveolärer Hypoxämie zugrunde liegen. Hinweise auf eine PAH gibt die Anamnese. Die Echokardiographie erlaubt die Diagnose und in vielen Fällen auch die Klärung der Ursache. Die invasive Untersuchung des Lungengefäßbetts ist die Basis für die Therapiestrategie.

Die Therapie richtet sich nach dem klinischen Bild (Funktionsstadien). Eine vasodilatative Therapie ist bei Kindern bei bis zu 20 - 40 % der Fälle, bei Erwachsenen jedoch nur bei 10 % möglich. Mehr als 60 % der Patieneten bedürfen einer antiproliferativen Behandlung. Behandlungserfolge sind eine Verlangsamung des fortschreitenden Krankheitsprozesses mit einer Verbesserung der Leistungsfähigkeit. Neue antiproliferative Behandlungskonzepte sind in Aussicht. Die Lungentransplantation ist noch keine Langzeitlösung.

Die Fortschritte im Gesamtmanagement der Erkrankung erfordern eine ständige Aktualisierung aller Empfehlungen. Aber schon jetzt gibt es feststehende Abläufe und Prioritäten zu Diagnostik und Therapie. Ziel ist es, die Diagnose „pulmonale Hypertonie” zu sichern, sie entsprechend der neuen Klassifikation zuzuordnen, die geeignetste der möglichen Therapieformen zu suchen und die Prognose einzuschätzen.

Literatur

  • 1 Abman S H, Accurso F J, Wilkening R B, Meschia G. Resistent fetal pulmonary hypoperfusion after acute hypoxia.  Am J Physiol. 1987;  253 H941-984
    PubMedGoogle Scholar
  • 2 Farber H W, Loscalzo J. Pulmonary Hypertension.  NEJM. 2004;  351 1655-1665
    CrossrefPubMedGoogle Scholar
  • 3 Simonneau G, Galie N, Rubin L J. et al . Clinical classification of pulmonary hypertension.  J Am Coll Cardiol. 2004;  43 (Suppl S) 5S-12S
    CrossrefPubMedGoogle Scholar
  • 4 Heath D, Edwards J E. The pathology of hypertensive pulmonary vascular changes in the pulmonary artery with special reference to congenital cardiac septal defect.  Circulation. 1958;  18 538-547
    PubMedGoogle Scholar
  • 5 Wagenvoort C A. Lung biopsy specimens in the evalution of pulmonary vascular disease.  Chest. 1980;  77 614-625
    CrossrefPubMedGoogle Scholar
  • 6 Rabinovitch M, Keane J F, Norwood W I, Castaneda A R, Reid L. Vascular structure in lung biopsy tissue correlated with pulmonary hemodynamic findings after repair of congenital heart defects.  Circulation. 1984;  69 655-667
    PubMedGoogle Scholar
  • 7 Voelkel N F, Cool C, Lee S D. et al . Primary pulmonary hypertension between inflammation and cancer.  Chest. 1998;  114 225S-230S
    CrossrefPubMedGoogle Scholar
  • 8 Black S M, Fineman J R, Steinhorn R H, Bristow J, Soifer S J. Increased endothelial NO synthase in lambs with increased pulmonary blood flow and hypertension.  Am J Physiol. 1998;  275 H1643-1651
    PubMedGoogle Scholar
  • 9 Ivy D D, Le Cras T D, Horan M P, Abman S H. Increased lung prepro ET-1 and decreased ETB-receptor gene expreression in fetal pulmonary hypertension.  Am J Physiol. 1998;  274 L535-541
    PubMedGoogle Scholar
  • 10 Grunig E, Janssen B, Mereles D. et al . Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene.  Circulation. 2000;  102 1145-1150
    CrossrefPubMedGoogle Scholar
  • 11 Grünig E, Koehler R, Miltenberger-Miltenyi G. et al . Primary Pulmonary Hypertension in Children May Have a Different Genetic Background Than in Adults.  Pediatr Res. 2004;  56 571-578
    CrossrefPubMedGoogle Scholar
  • 12 PPH International Consortium . Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension.  Nat Genet. 2000;  26 81-84
    CrossrefPubMedGoogle Scholar
  • 13 Deng Z, Morse J H, Slager S L. et al . Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene.  Am J Hum Genet. 2000;  67 737-744
    CrossrefPubMedGoogle Scholar
  • 14 Nichols W, KollerD , Slovis B. et al . Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31 - 32.  Nat Genet. 1997;  15 277-280
    CrossrefPubMedGoogle Scholar
  • 15 Machado R D, Pauciulo M W, Thomson J R. et al . BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension.  Am J Hum Genet. 2001;  68 92-102
    CrossrefPubMedGoogle Scholar
  • 16 Zhou S, Kinzler K W, Vogelstein B. Going mad with Smads.  N Engl J Med. 1999;  341 1144-1146
    CrossrefPubMedGoogle Scholar
  • 17 Scott J. Pulling apart pulmonary hypertension.  Nature genetics. 2000;  26 3-4
    CrossrefPubMedGoogle Scholar
  • 18 Lopes A A, Maeda N Y, Bydlowski S P. Abnormalities in circulating von Willebrand factor and survival in pulmonary hypertension.  Am J Med. 1998;  105 21-26
    CrossrefPubMedGoogle Scholar
  • 19 Herve P, Launay J M, Scrobohaci M L. et al . Increased plasma serotonin in primary pulmonary hypertension.  Am J Med. 1995;  99 249-254
    CrossrefPubMedGoogle Scholar
  • 20 Lüscher T F. et al . Interactions between endothelium-derived relaxing and contracting factors in health and cardiovascular disease.  Circulation. 1993;  87 (Suppl V) 36-44
    PubMedGoogle Scholar
  • 21 Christman B, McPherson C, Newman J. et al . An imbalance between the excretion of thromboxane and Prostacyclin metabolites in pulmonary hypertension.  N Engl J 1992;. Med;  327 70-75
    PubMedGoogle Scholar
  • 22 Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension.  N Engl J Med. 1995;  333 214-221
    CrossrefPubMedGoogle Scholar
  • 23 Langleben D. et al . Endothelin-1 in acute lung injury and the adult respiratory distress syndrome.  Am Rev Respir Dis. 1993;  148 1646-1650
    PubMedGoogle Scholar
  • 24 Yuan X-J, Wang J, Juhaszova M, Gaine S, Rubin L. Attenuated K+ channel gene transcription in primary pulmonary hypertension.  Lancet. 1998;  352 726-727
    CrossrefPubMedGoogle Scholar
  • 25 Yuan X-J, Aldinger A M, Juhaszova M. et al . Dysfunctional voltage-gated K+ channel in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension.  Circulation. 1998;  98 1400-1406
    CrossrefPubMedGoogle Scholar
  • 26 Zimermann R, Kreuder J, Michel-Behnke I, Voelkel N F, Schranz D. Pulmonary flow reserve: a study of children with idiopathic Pulmonary Arterial Hypertension.  . 2006;  in press
    PubMedGoogle Scholar
  • 27 Craig R J, Seltzer A. Natural history and prognosis of atrial septal defect.  Circulation. 1968;  37 805-815
    PubMedGoogle Scholar
  • 28 Hopkins W E, Ochoa L L, Richardson G W, Trulock E P. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome.  J Heart Lung Transplant. 1996;  15(1 Pt 1) 100-105
    PubMedGoogle Scholar
  • 29 Sandoval J, Bauerle O, Gomez A. et al . Primary pulmonary hypertension in children: clinical characterization and survival.  J Am Coll Cardiol. 1995;  25 466-474
    CrossrefPubMedGoogle Scholar
  • 30 D’Alonzo G, Barst R J, Ayres S M. et al . Survival in patients with primary pulmonary hypertension: results from a national prospective registry.  Ann Intern Med. 1991;  115 343-349
    PubMedGoogle Scholar
  • 31 Rubin L J. Primary pulmonary hypertension.  Chest. 1993;  104 236-250
    PubMedGoogle Scholar
  • 32 King M E. et al . Interventricular septal configuration as a predictor of right ventricular systolic hypertension in children: a cross-sectional echocardiographic study.  Circulation. 1983;  68 68-75
    CrossrefPubMedGoogle Scholar
  • 33 Kitabatake A. et al . Noninvasive evaluation of pulmonary hypertension by a pulsed Doppler technique.  Circulation. 1983;  68 302-309
    CrossrefPubMedGoogle Scholar
  • 34 Schmitz-Rode T, Janssens U, Duda S H. et al . Massive pulmonary embolism: percutaneous emergency treatment by pigtail rotation catheter.  J Am Coll Cardiol. 2000;  36(2) 375-380
    CrossrefPubMedGoogle Scholar
  • 35 Feinstein J A, Goldhaber S Z, Lock J E. et al . Balloon Pulmonary Angioplasty for Treatment of Chronic Thromboembolic Pulmonary Hypertension.  Circulation. 2001;  103 10-14
    CrossrefPubMedGoogle Scholar
  • 36 Celermajer D S, Cullen S, Deanfield J E. Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics.  Circulation. 1993;  87 440-446
    PubMedGoogle Scholar
  • 37 Raffy O, Azarian R, Brenot F. et al . Clinical significance of the pulmonary vasodilator response during short-term infusion of Prostacyclin in primary pulmonary hypertension.  Circulation. 1996;  93 484-488
    PubMedGoogle Scholar
  • 38 Palevski H I. et al . Primary pulmonary hypertension vascular structure, morphometry, and responsiveness to vasodilator agents.  Circulation. 1989;  80 1207-1221
    PubMedGoogle Scholar
  • 39 Germann P, Braschi A, Della Rocca G. et al . Inhaled nitric oxide therapy in adults.  European expert recommendations; Intensive Care Med.. 2005;  31(8) 1029-1041
    PubMedGoogle Scholar
  • 40 Houde C. et al . Profile of paediatric patients with pulmonary hypertension judged by responsiveness to vasodilators.  Br Heart J. 1993;  70 461-468
    PubMedGoogle Scholar
  • 41 Wessel D, Adatia I, Giglia T M. et al . Use of inhaled nitric oxide and acetylcholine in the evalution of pulmonary hypertension and endothelial function after cardiopulmonary bypass.  Circulation. 1993;  88 2128-2138
    PubMedGoogle Scholar
  • 42 Rimensberger P C, Spahr-Schopfer I, Berner M. et al . Inhaled Nitric Oxide versus aerosolized Iloprost in secondary pulmonary hypertension in children with congenital heart disease.  Circulation. 2001;  103 544-548
    CrossrefPubMedGoogle Scholar
  • 43 Tarpy S P, Celli B R. Long-term oxygen therapy.  N Engl J Med. 1995;  333 710-714
    CrossrefPubMedGoogle Scholar
  • 44 The STOP-ROP Multicenter Study Group . Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomised, controlled trial. I: primary outcomes.  Pediatrics. 2000;  105 295-310
    CrossrefPubMedGoogle Scholar
  • 45 Benisty J I, Landzberg M J. Eisenmenger’s Syndrome.  Curr Treat Options Cardiovasc Med. 1999;  1 355-362
    PubMedGoogle Scholar
  • 46 Berman E B, Barst R J. Eisenmenger’s syndrome: current management.  Prog Cardiovasc Dis. 2002;  45 129-138
    CrossrefPubMedGoogle Scholar
  • 47 Rich S, Kaufmann E, Levy P S. The effects of high doses of calcium-channel blockers on survival in primary pulmonary hypertension.  N Engl J Med. 1992;  327 76-81
    CrossrefPubMedGoogle Scholar
  • 48 Rubin L J. Primary ulmonary hypertension.  N Engl J Med. 1997;  336 111-117
    CrossrefPubMedGoogle Scholar
  • 49 Ghofrani H A, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension.  NEJM. 2005;  353 1412-1413
    CrossrefPubMedGoogle Scholar
  • 50 Barst R J, McGoon M, Torbicki A, Sitbon O, Krowka M J, Olschewski H. et al . Diagnosis and differential assessment of pulmonary arterial hypertension.  J Am Coll Cardiol. 2004;  43(12 Suppl S) 40S-47S
    CrossrefPubMedGoogle Scholar
  • 51 Ghofrani H A, Wiedemann R, Rose F, Schermuly R T, Olschewski H, Weissmann N. et al . Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial.  Lancet. 2002;  360 895-900
    CrossrefPubMedGoogle Scholar
  • 52 Sastry B K, Narasimhan C, Reddy N K, Raju B S. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study.  J Am Coll Cardiol. 2004;  43 1149-1153
    PubMedGoogle Scholar
  • 53 Ghofrani H A, Schermuly R T, Rose F, Wiedemann R, Kohstall M G, Kreckel A. et al . Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension.  Am J Respir Crit Care Med. 2003;  167 1139-1141
    PubMedGoogle Scholar
  • 54 Ghofrani H A, Rose F, Schermuly R T, Olschewski H, Wiedemann R, Kreckel A. et al . Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension.  J Am Coll Cardiol. 2003;  42 158-164
    CrossrefPubMedGoogle Scholar
  • 55 MacLean M R. Endothelin-1: a mediator of pulmonary hypertension?.  Pulm Pharmacol Ther. 1998;  11 125-132
    PubMedGoogle Scholar
  • 56 Michel T, Feron O. Nitric oxide synthases: which, where, how, and why.  J Clin Invest. 1997;  100 2146-2151
    CrossrefPubMedGoogle Scholar
  • 57 Channick R N, Simmonneau G, Sitbon O. et al . Effects of the dual Endothelin-receptor antagonist Bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.  Lancet. 2001;  358 1119-1123
    CrossrefPubMedGoogle Scholar
  • 58 Hoeper M M, Taha N, Bekjarova A, Gatzke R, Spiekerkoetter E. Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids.  Eur Respir J. 2003;  22 330-334
    CrossrefPubMedGoogle Scholar
  • 59 Williamson D J, Wallman L L, Jones R. et al . Hemodynamic effects of Bosentan, an Endothelin receptor antagonist, in patients with pulmonary hypertension.  Circulation. 2000;  102 411-418
    PubMedGoogle Scholar
  • 60 Sitbon O, Gressin V, Speich R, Macdonald P S, Opravil M, Cooper D A. et al . Bosentan for Human Immunodeficiency Virus-associated Pulmonary Arterial Hypertension.  Am J Respir Crit Care Med. 2004;  170 1212-1217
    CrossrefPubMedGoogle Scholar
  • 61 Barst R J, Rubin L J, Long W A. et al . A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.  N Engl J Med. 1996;  334 296-301
    CrossrefPubMedGoogle Scholar
  • 62 Nagaya N, Uematsu M, Okano Y. et al . Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension.  J Am Coll Cardiol. 1999;  34 1188-1192
    CrossrefPubMedGoogle Scholar
  • 63 Higenbottam T W, Spiegelhalter D, Scott J P. et al . Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension.  Br Heart. 1993;  J 70 366-370
    PubMedGoogle Scholar
  • 64 Conte J V, Gaine S P, Orens J B. et al . The influence of continuous intravenous Prostacyclin therapy for primary pulmonary hypertension on the timing and outcome of transplantation.  J Heart Lung Transplant. 1998;  17 679-685
    PubMedGoogle Scholar
  • 65 Rosenzweig E B, Kerstein D, Barst R J. Long-Term Prostacyclin for pulmonary hypertension with associated congenital heart defects.  Circulation. 1999;  99 1858-1865
    CrossrefPubMedGoogle Scholar
  • 66 Higenbottam T W, Butt A Y, McMahon . et al . Long term intravenous prostaglandin (epoprostenol or Iloprost) for treatment of severe pulmonary hypertension.  Heart. 1998;  80 151-155
    PubMedGoogle Scholar
  • 67 Olschewski H, Walmrath D, Schermuly R. et al . Aerosolized Prostacyclin and Iloprost in severe pulmonary hypertension.  Ann Intern Med. 1996;  124 820-824
    PubMedGoogle Scholar
  • 68 Olschewski H, Ghofrani H A, Schmehl T. et al . Inhaled Iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH study group.  Ann Intern Med. 2000;  132 435-443
    PubMedGoogle Scholar
  • 69 Hoeper M M, Schwarze M, Ehlerding S. et al . Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue.  N Engl J Med. 2000;  342 1866-1870
    CrossrefPubMedGoogle Scholar
  • 70 Grimminger F, Rose F, Ghofrani H A. et al . Inhalative Strategien zur Verbesserung der pulmonalen Hämodynamik und des Gasaustausches bei Sepsis und schwerer pulmonaler Hypertonie.  Z Kardiol. 2000;  89 477-484
    CrossrefPubMedGoogle Scholar
  • 71 Rich S, Lam W. Atrial septostomy as palliative therapy for refractory primary pulmonary hypertension.  Am J Cardiol. 1983;  51 1560-1561
    CrossrefPubMedGoogle Scholar
  • 72 Kerstein D, Levy P S, Hsu D T. et al . Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension.  Circulation. 1995;  91 2028-2035
    PubMedGoogle Scholar
  • 73 Reichenberger F, Pepke-Zaba J, McNeil K, Parameshwar J, Shapiro L M. Atrial septostomy in the treatment of severe pulmonary arterial hypertension.  Thorax. 2003;  58 797-800
    CrossrefPubMedGoogle Scholar
  • 74 Niedermeyer J, Harringer W, Höper M W. et al . Lungentransplantation in Hannover: eine Zwischenbilanz nach 10 Jahren.  Pneumologie. 1999;  53 157-163
    PubMedGoogle Scholar
  • 75 Chen J M, Levin H R, Michler R E, Prusmack C J, Rose E A, Aaronson K D. Reevaluating the significance of pulmonary hypertension before cardiac transplantation: determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality.  J Thorac Cardiovasc Surg. 1997;  114 627-634
    PubMedGoogle Scholar
  • 76 Natale M E, Pina I L. Evaluation of pulmonary hypertension in heart transplant candidates.  Curr Opin Cardiol. 2003;  18(2) 136-140
    CrossrefPubMedGoogle Scholar
  • 77 Frostell C, Fratacci M D, Wain J C. et al . Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.  Circulation. 1991;  83 2038-2047
    PubMedGoogle Scholar
  • 78 Slawsky M T, Colucci W S, Gottlieb S S, Greenberg B H, Haeusslein E, Hare J. et al . Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators.  Circulation. 2000;  102 2222-2227
    CrossrefPubMedGoogle Scholar
  • 79 Follath F, Cleland J G, Just H, Papp J G, Scholz H, Peuhkurinen K. et al . Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial.  Lancet. 2002;  360 196-202
    CrossrefPubMedGoogle Scholar

Prof. Dr. med. Dietmar Schranz

Kinderherzzentrum

Justus-Liebig-Universität · Feulgenstr. 12 · 35392 Gießen

Fax: 0641/99-43461

Email: Dietmar.Schranz@paediat.med.uni-giessen.de