Download PDF
Eur J Pediatr Surg 2012; 22(05): 374-383
DOI: 10.1055/s-0032-1329531
Review
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management of Pulmonary Hypertension in Neonates with Congenital Diaphragmatic Hernia

S. Vijfhuize
1   Departments of Pediatric Surgery, Neonatology, and Intensive Care, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands
,
T. Schaible
2   Department of Intensive Care, Kinderklinikum Mannheim, Mannheim, Germany
,
U. Kraemer
1   Departments of Pediatric Surgery, Neonatology, and Intensive Care, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands
,
T. E. Cohen-Overbeek
3   Division of Prenatal Medicine, Department of Obstetrics and Gynaecology, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands
,
D. Tibboel
1   Departments of Pediatric Surgery, Neonatology, and Intensive Care, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands
,
I. Reiss
1   Departments of Pediatric Surgery, Neonatology, and Intensive Care, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

10 September 2012

17 September 2012

Publication Date:
31 October 2012 (online)

    Permissions and Reprints

Abstract

Pulmonary hypertension associated with congenital diaphragmatic hernia is still one of the major challenges in neonatal intensive care units. Several relevant pathways in its pathogenesis have been described and studied, but the absence of well-designed randomized controlled trials and the scattered data on the pharmacokinetics and pharmacodynamics of most of the drugs used in these patients hamper progress significantly. This review aims to give an overview of current management strategies in the antenatal and neonatal phase, and provides founded clinical recommendations.

Keywords

congenital diaphragmatic hernia - pulmonary hypertension - neonates - NO pathway
 

  • References

  • 1 Lally KP, Engle W. American Academy of Pediatrics Section on Surgery; American Academy of Pediatrics Committee on Fetus and Newborn. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics 2008; 121 (3) 627-632
    CrossrefPubMedGoogle Scholar
  • 2 Bagolan P, Morini F. Long-term follow up of infants with congenital diaphragmatic hernia. Semin Pediatr Surg 2007; 16 (2) 134-144
    CrossrefPubMedGoogle Scholar
  • 3 Trachsel D, Selvadurai H, Bohn D, Langer JC, Coates AL. Long-term pulmonary morbidity in survivors of congenital diaphragmatic hernia. Pediatr Pulmonol 2005; 39 (5) 433-439
    CrossrefPubMedGoogle Scholar
  • 4 van den Hout L, Schaible T, Cohen-Overbeek TE , et al. Actual outcome in infants with congenital diaphragmatic hernia: the role of a standardized postnatal treatment protocol. Fetal Diagn Ther 2011; 29 (1) 55-63
    CrossrefPubMedGoogle Scholar
  • 5 Jeffery TK, Wanstall JC. Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension. Pharmacol Ther 2001; 92 (1) 1-20
    CrossrefPubMedGoogle Scholar
  • 6 Stenmark KR, Fagan KA, Frid MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res 2006; 99 (7) 675-691
    CrossrefPubMedGoogle Scholar
  • 7 Okoye BO, Losty PD, Fisher MJ, Wilmott I, Lloyd DA. Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 1998; 78 (3) F204-F208
    CrossrefPubMedGoogle Scholar
  • 8 Abman SH, Ivy DD. Recent progress in understanding pediatric pulmonary hypertension. Curr Opin Pediatr 2011; 23 (3) 298-304
    CrossrefPubMedGoogle Scholar
  • 9 Giaid A, Yanagisawa M, Langleben D , et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328 (24) 1732-1739
    CrossrefPubMedGoogle Scholar
  • 10 Kobayashi H, Puri P. Plasma endothelin levels in congenital diaphragmatic hernia. J Pediatr Surg 1994; 29 (9) 1258-1261
    CrossrefPubMedGoogle Scholar
  • 11 de Lagausie P, de Buys-Roessingh A, Ferkdadji L , et al. Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia. J Pathol 2005; 205 (1) 112-118
    CrossrefPubMedGoogle Scholar
  • 12 Dingemann J, Doi T, Ruttenstock E, Puri P. Upregulation of endothelin receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation. Pediatr Surg Int 2010; 26 (1) 65-69
    CrossrefPubMedGoogle Scholar
  • 13 Rosenberg AA, Kennaugh J, Koppenhafer SL, Loomis M, Chatfield BA, Abman SH. Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension. J Pediatr 1993; 123 (1) 109-114
    PubMedGoogle Scholar
  • 14 Datin-Dorriere V, Rouzies S, Taupin P , et al. Prenatal prognosis in isolated congenital diaphragmatic hernia. Am J Obstet Gynecol 2008; 198 (1) 80 , e1–e5
    PubMedGoogle Scholar
  • 15 Deprest J, Jani J, Van Schoubroeck D , et al. Current consequences of prenatal diagnosis of congenital diaphragmatic hernia. J Pediatr Surg 2006; 41 (2) 423-430
    CrossrefPubMedGoogle Scholar
  • 16 Keller RL. Antenatal and postnatal lung and vascular anatomic and functional studies in congenital diaphragmatic hernia: implications for clinical management. Am J Med Genet C Semin Med Genet 2007; 145C (2) 184-200
    CrossrefPubMedGoogle Scholar
  • 17 Jani J, Keller RL, Benachi A , et al; Antenatal-CDH-Registry Group. Prenatal prediction of survival in isolated left-sided diaphragmatic hernia. Ultrasound Obstet Gynecol 2006; 27 (1) 18-22
    PubMedGoogle Scholar
  • 18 Ba'ath ME, Jesudason EC, Losty PD. How useful is the lung-to-head ratio in predicting outcome in the fetus with congenital diaphragmatic hernia? A systematic review and meta-analysis. Ultrasound Obstet Gynecol 2007; 30 (6) 897-906
    CrossrefPubMedGoogle Scholar
  • 19 Metkus AP, Filly RA, Stringer MD, Harrison MR, Adzick NS. Sonographic predictors of survival in fetal diaphragmatic hernia. J Pediatr Surg 1996; 31 (1) 148-151 , discussion 151–152
    CrossrefPubMedGoogle Scholar
  • 20 Jani J, Nicolaides KH, Keller RL , et al; Antenatal-CDH-Registry Group. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol 2007; 30 (1) 67-71
    CrossrefPubMedGoogle Scholar
  • 21 Ruano R, Benachi A, Martinovic J , et al. Can three-dimensional ultrasound be used for the assessment of the fetal lung volume in cases of congenital diaphragmatic hernia?. Fetal Diagn Ther 2004; 19 (1) 87-91
    CrossrefPubMedGoogle Scholar
  • 22 Peralta CF, Jani J, Cos T, Nicolaides KH, Deprest J. Left and right lung volumes in fetuses with diaphragmatic hernia. Ultrasound Obstet Gynecol 2006; 27 (5) 551-554
    CrossrefPubMedGoogle Scholar
  • 23 Harrison MR, Langer JC, Adzick NS , et al. Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience. J Pediatr Surg 1990; 25 (1) 47-55 , discussion 56–57
    CrossrefPubMedGoogle Scholar
  • 24 Mullassery D, Ba'ath ME, Jesudason EC, Losty PD. Value of liver herniation in prediction of outcome in fetal congenital diaphragmatic hernia: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2010; 35 (5) 609-614
    CrossrefPubMedGoogle Scholar
  • 25 Ruano R, Takashi E, da Silva MM, Campos JA, Tannuri U, Zugaib M. Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters. Ultrasound Obstet Gynecol 2012; 39 (1) 42-49
    CrossrefPubMedGoogle Scholar
  • 26 Sokol J, Shimizu N, Bohn D, Doherty D, Ryan G, Hornberger LK. Fetal pulmonary artery diameter measurements as a predictor of morbidity in antenatally diagnosed congenital diaphragmatic hernia: a prospective study. Am J Obstet Gynecol 2006; 195 (2) 470-477
    CrossrefPubMedGoogle Scholar
  • 27 Thébaud B, Azancot A, de Lagausie P , et al. Congenital diaphragmatic hernia: antenatal prognostic factors. Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia?. Intensive Care Med 1997; 23 (10) 10062-10069
    PubMedGoogle Scholar
  • 28 Coakley FV, Lopoo JB, Lu Y , et al. Normal and hypoplastic fetal lungs: volumetric assessment with prenatal single-shot rapid acquisition with relaxation enhancement MR imaging. Radiology 2000; 216 (1) 107-111
    PubMedGoogle Scholar
  • 29 Rypens F, Metens T, Rocourt N , et al. Fetal lung volume: estimation at MR imaging-initial results. Radiology 2001; 219 (1) 236-241
    CrossrefPubMedGoogle Scholar
  • 30 Mahieu-Caputo D, Sonigo P, Dommergues M , et al. Fetal lung volume measurement by magnetic resonance imaging in congenital diaphragmatic hernia. BJOG 2001; 108 (8) 863-868
    PubMedGoogle Scholar
  • 31 Cannie M, Jani J, Meersschaert J , et al. Prenatal prediction of survival in isolated diaphragmatic hernia using observed to expected total fetal lung volume determined by magnetic resonance imaging based on either gestational age or fetal body volume. Ultrasound Obstet Gynecol 2008; 32 (5) 633-639
    CrossrefPubMedGoogle Scholar
  • 32 Ruano R, Aubry MC, Barthe B, Mitanchez D, Dumez Y, Benachi A. Quantitative analysis of fetal pulmonary vasculature by 3-dimensional power Doppler ultrasonography in isolated congenital diaphragmatic hernia. Am J Obstet Gynecol 2006; 195 (6) 1720-1728
    CrossrefPubMedGoogle Scholar
  • 33 Mahieu-Caputo D, Aubry MC, El Sayed M, Joubin L, Thalabard JC, Dommergues M. Evaluation of fetal pulmonary vasculature by power Doppler imaging in congenital diaphragmatic hernia. J Ultrasound Med 2004; 23 (8) 1011-1017
    PubMedGoogle Scholar
  • 34 Fuke S, Kanzaki T, Mu J , et al. Antenatal prediction of pulmonary hypoplasia by acceleration time/ejection time ratio of fetal pulmonary arteries by Doppler blood flow velocimetry. Am J Obstet Gynecol 2003; 188 (1) 228-233
    CrossrefPubMedGoogle Scholar
  • 35 Chaoui R, Kalache K, Tennstedt C, Lenz F, Vogel M. Pulmonary arterial Doppler velocimetry in fetuses with lung hypoplasia. Eur J Obstet Gynecol Reprod Biol 1999; 84 (2) 179-185
    CrossrefPubMedGoogle Scholar
  • 36 Cruz-Martinez R, Moreno-Alvarez O, Hernandez-Andrade E , et al. Contribution of intrapulmonary artery Doppler to improve prediction of survival in fetuses with congenital diaphragmatic hernia treated with fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol 2010; 35 (5) 572-577
    CrossrefPubMedGoogle Scholar
  • 37 Laudy JA, Gaillard JL, vd Anker JN, Tibboel D, Wladimiroff JW. Doppler ultrasound imaging: a new technique to detect lung hypoplasia before birth?. Ultrasound Obstet Gynecol 1996; 7 (3) 189-192
    CrossrefPubMedGoogle Scholar
  • 38 Moreno-Alvarez O, Hernandez-Andrade E, Oros D, Jani J, Deprest J, Gratacos E. Association between intrapulmonary arterial Doppler parameters and degree of lung growth as measured by lung-to-head ratio in fetuses with congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 2008; 31 (2) 164-170
    CrossrefPubMedGoogle Scholar
  • 39 Cruz-Martinez R, Hernandez-Andrade E, Moreno-Alvarez O, Done E, Deprest J, Gratacos E. Prognostic value of pulmonary Doppler to predict response to tracheal occlusion in fetuses with congenital diaphragmatic hernia. Fetal Diagn Ther 2011; 29 (1) 18-24
    CrossrefPubMedGoogle Scholar
  • 40 Broth RE, Wood DC, Rasanen J , et al. Prenatal prediction of lethal pulmonary hypoplasia: the hyperoxygenation test for pulmonary artery reactivity. Am J Obstet Gynecol 2002; 187 (4) 940-945
    CrossrefPubMedGoogle Scholar
  • 41 Done E, Allegaert K, Lewi P , et al. Maternal hyperoxygenation test in fetuses undergoing FETO for severe isolated congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 2011; 37 (3) 264-271
    CrossrefPubMedGoogle Scholar
  • 42 Stressig R, Fimmers R, Eising K, Gembruch U, Kohl T. Preferential streaming of the ductus venosus and inferior caval vein towards the right heart is associated with left heart underdevelopment in human fetuses with left-sided diaphragmatic hernia. Heart 2010; 96 (19) 1564-1568
    CrossrefPubMedGoogle Scholar
  • 43 Suen HC, Bloch KD, Donahoe PK. Antenatal glucocorticoid corrects pulmonary immaturity in experimentally induced congenital diaphragmatic hernia in rats. Pediatr Res 1994; 35 (5) 523-529
    CrossrefPubMedGoogle Scholar
  • 44 Suen HC, Losty P, Donahoe PK, Schnitzer JJ. Combined antenatal thyrotropin-releasing hormone and low-dose glucocorticoid therapy improves the pulmonary biochemical immaturity in congenital diaphragmatic hernia. J Pediatr Surg 1994; 29 (2) 359-363
    CrossrefPubMedGoogle Scholar
  • 45 Guarino N, Puri P. Antenatal dexamethasone enhances endothelin-1 synthesis and gene expression in the heart in congenital diaphragmatic hernia in rats. J Pediatr Surg 2002; 37 (11) 1563-1567
    CrossrefPubMedGoogle Scholar
  • 46 Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement 1994; 12 (2) 1-24
    PubMedGoogle Scholar
  • 47 Lally KP, Bagolan P, Hosie S , et al; Congenital Diaphragmatic Hernia Study Group. Corticosteroids for fetuses with congenital diaphragmatic hernia: can we show benefit?. J Pediatr Surg 2006; 41 (4) 668-674 , discussion 668–674
    CrossrefPubMedGoogle Scholar
  • 48 DiFiore JW, Fauza DO, Slavin R, Peters CA, Fackler JC, Wilson JM. Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia. J Pediatr Surg 1994; 29 (2) 248-256 , discussion 256–257
    CrossrefPubMedGoogle Scholar
  • 49 Khan PA, Cloutier M, Piedboeuf B. Tracheal occlusion: a review of obstructing fetal lungs to make them grow and mature. Am J Med Genet C Semin Med Genet 2007; 145C (2) 125-138
    CrossrefPubMedGoogle Scholar
  • 50 Harrison MR, Keller RL, Hawgood SB , et al. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med 2003; 349 (20) 1916-1924
    CrossrefPubMedGoogle Scholar
  • 51 Breysem L, Debeer A, Claus F , et al. Cross-sectional study of tracheomegaly in children after fetal tracheal occlusion for severe congenital diaphragmatic hernia. Radiology 2010; 257 (1) 226-232
    CrossrefPubMedGoogle Scholar
  • 52 Deprest J, Breysem L, Gratacos E , et al. Tracheal side effects following fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia. Pediatr Radiol 2010; 40 (5) 670-673
    CrossrefPubMedGoogle Scholar
  • 53 Deprest J, Nicolaides K, Done' E , et al. Technical aspects of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia. J Pediatr Surg 2011; 46 (1) 22-32
    CrossrefPubMedGoogle Scholar
  • 54 Reiss I, Schaible T, van den Hout L , et al; CDH EURO Consortium. Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus. Neonatology 2010; 98 (4) 354-364
    CrossrefPubMedGoogle Scholar
  • 55 Davis PG, Tan A, O'Donnell CP, Schulze A. Resuscitation of newborn infants with 100% oxygen or air: a systematic review and meta-analysis. Lancet 2004; 364 (9442) 1329-1333
    CrossrefPubMedGoogle Scholar
  • 56 Pejovic B, Peco-Antic A, Marinkovic-Eric J. Blood pressure in non-critically ill preterm and full-term neonates. Pediatr Nephrol 2007; 22 (2) 249-257
    PubMedGoogle Scholar
  • 57 Carbajal R, Eble B, Anand KJ. Premedication for tracheal intubation in neonates: confusion or controversy?. Semin Perinatol 2007; 31 (5) 309-317
    CrossrefPubMedGoogle Scholar
  • 58 Masumoto K, Nagata K, Uesugi T, Yamada T, Taguchi T. Risk factors for sensorineural hearing loss in survivors with severe congenital diaphragmatic hernia. Eur J Pediatr 2007; 166 (6) 607-612
    CrossrefPubMedGoogle Scholar
  • 59 Keller RL, Tacy TA, Hendricks-Munoz K , et al. Congenital diaphragmatic hernia: endothelin-1, pulmonary hypertension, and disease severity. Am J Respir Crit Care Med 2010; 182 (4) 555-561
    CrossrefPubMedGoogle Scholar
  • 60 Dillon PW, Cilley RE, Mauger D, Zachary C, Meier A. The relationship of pulmonary artery pressure and survival in congenital diaphragmatic hernia. J Pediatr Surg 2004; 39 (3) 307-312 , discussion 307–312
    CrossrefPubMedGoogle Scholar
  • 61 Reisner SA, Azzam Z, Halmann M , et al. Septal/free wall curvature ratio: a noninvasive index of pulmonary arterial pressure. J Am Soc Echocardiogr 1994; 7 (1) 27-35
    PubMedGoogle Scholar
  • 62 Dong SJ, Smith ER, Tyberg JV. Changes in the radius of curvature of the ventricular septum at end diastole during pulmonary arterial and aortic constrictions in the dog. Circulation 1992; 86 (4) 1280-1290
    CrossrefPubMedGoogle Scholar
  • 63 Takahashi S, Oishi Y, Ito N , et al. Evaluating mortality and disease severity in congenital diaphragmatic hernia using the McGoon and pulmonary artery indices. J Pediatr Surg 2009; 44 (11) 2101-2106
    CrossrefPubMedGoogle Scholar
  • 64 Boloker J, Bateman DA, Wung JT, Stolar CJ. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair. J Pediatr Surg 2002; 37 (3) 357-366
    CrossrefPubMedGoogle Scholar
  • 65 Logan JW, Cotten CM, Goldberg RN, Clark RH. Mechanical ventilation strategies in the management of congenital diaphragmatic hernia. Semin Pediatr Surg 2007; 16 (2) 115-125
    CrossrefPubMedGoogle Scholar
  • 66 Wung JT, Sahni R, Moffitt ST, Lipsitz E, Stolar CJ. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995; 30 (3) 406-409
    CrossrefPubMedGoogle Scholar
  • 67 Bagolan P, Casaccia G, Crescenzi F, Nahom A, Trucchi A, Giorlandino C. Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia. J Pediatr Surg 2004; 39 (3) 313-318 , discussion 313–318
    CrossrefPubMedGoogle Scholar
  • 68 Downard CD, Jaksic T, Garza JJ , et al. Analysis of an improved survival rate for congenital diaphragmatic hernia. J Pediatr Surg 2003; 38 (5) 729-732
    CrossrefPubMedGoogle Scholar
  • 69 Finer NN, Tierney A, Etches PC, Peliowski A, Ainsworth W. Congenital diaphragmatic hernia: developing a protocolized approach. J Pediatr Surg 1998; 33 (9) 1331-1337
    CrossrefPubMedGoogle Scholar
  • 70 Frenckner B, Ehrén H, Granholm T, Lindén V, Palmér K. Improved results in patients who have congenital diaphragmatic hernia using preoperative stabilization, extracorporeal membrane oxygenation, and delayed surgery. J Pediatr Surg 1997; 32 (8) 1185-1189
    CrossrefPubMedGoogle Scholar
  • 71 Kays DW, Langham Jr MR, Ledbetter DJ, Talbert JL. Detrimental effects of standard medical therapy in congenital diaphragmatic hernia. Ann Surg 1999; 230 (3) 340-348 , discussion 348–351
    CrossrefPubMedGoogle Scholar
  • 72 Reyes C, Chang LK, Waffarn F, Mir H, Warden MJ, Sills J. Delayed repair of congenital diaphragmatic hernia with early high-frequency oscillatory ventilation during preoperative stabilization. J Pediatr Surg 1998; 33 (7) 1010-1014 , discussion 1014–1016
    CrossrefPubMedGoogle Scholar
  • 73 Weber TR, Kountzman B, Dillon PA, Silen ML. Improved survival in congenital diaphragmatic hernia with evolving therapeutic strategies. Arch Surg 1998; 133 (5) 498-502 , discussion 502–503
    CrossrefPubMedGoogle Scholar
  • 74 Wilson JM, Lund DP, Lillehei CW, Vacanti JP. Congenital diaphragmatic hernia—a tale of two cities: the Boston experience. J Pediatr Surg 1997; 32 (3) 401-405
    CrossrefPubMedGoogle Scholar
  • 75 Bohn D. Congenital diaphragmatic hernia. Am J Respir Crit Care Med 2002; 166 (7) 911-915
    CrossrefPubMedGoogle Scholar
  • 76 Ssemakula N, Stewart DL, Goldsmith LJ, Cook LN, Bond SJ. Survival of patients with congenital diaphragmatic hernia during the ECMO era: an 11-year experience. J Pediatr Surg 1997; 32 (12) 1683-1689
    CrossrefPubMedGoogle Scholar
  • 77 Osiovich HC. Improving survival of neonates with isolated congenital diaphragmatic hernia. Indian Pediatr 2004; 41 (11) 1138-1142
    PubMedGoogle Scholar
  • 78 Somaschini M, Locatelli G, Salvoni L, Bellan C, Colombo A. Impact of new treatments for respiratory failure on outcome of infants with congenital diaphragmatic hernia. Eur J Pediatr 1999; 158 (10) 780-784
    CrossrefPubMedGoogle Scholar
  • 79 Cacciari A, Ruggeri G, Mordenti M , et al. High-frequency oscillatory ventilation versus conventional mechanical ventilation in congenital diaphragmatic hernia. Eur J Pediatr Surg 2001; 11 (1) 3-7
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Henderson-Smart DJ, De Paoli AG, Clark RH, Bhuta T. High frequency oscillatory ventilation versus conventional ventilation for infants with severe pulmonary dysfunction born at or near term. Cochrane Database Syst Rev 2009; (3) CD002974
    PubMedGoogle Scholar
  • 81 van den Hout L, Tibboel D, Vijfhuize S, te Beest H, Hop W, Reiss I. CDH-EURO Consortium. The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial. BMC Pediatr 2011; 11: 98
    CrossrefPubMedGoogle Scholar
  • 82 Ng PC, Lee CH, Bnur FL , et al. A double-blind, randomized, controlled study of a “stress dose” of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics 2006; 117 (2) 367-375
    CrossrefPubMedGoogle Scholar
  • 83 Steinhorn RH. Therapeutic approaches using nitric oxide in infants and children. Free Radic Biol Med 2011; 51 (5) 1027-1034
    CrossrefPubMedGoogle Scholar
  • 84 Finer NN, Etches PC, Kamstra B, Tierney AJ, Peliowski A, Ryan CA. Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response. J Pediatr 1994; 124 (2) 302-308
    PubMedGoogle Scholar
  • 85 Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992; 340 (8823) 819-820
    CrossrefPubMedGoogle Scholar
  • 86 Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2001; (4) CD000399
    PubMedGoogle Scholar
  • 87 The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics 1997; 99 (6) 838-845
    CrossrefPubMedGoogle Scholar
  • 88 Fineman JR, Zwass MS. Inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn. Acta Paediatr Jpn 1995; 37 (4) 425-430
    CrossrefPubMedGoogle Scholar
  • 89 Stocker C, Penny DJ, Brizard CP, Cochrane AD, Soto R, Shekerdemian LS. Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery. Intensive Care Med 2003; 29 (11) 1996-2003
    CrossrefPubMedGoogle Scholar
  • 90 Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 2006; 117 (4) 1077-1083
    CrossrefPubMedGoogle Scholar
  • 91 Noori S, Friedlich P, Wong P, Garingo A, Seri I. Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension. Neonatology 2007; 91 (2) 92-100
    CrossrefPubMedGoogle Scholar
  • 92 Hunter L, Richens T, Davis C, Walker G, Simpson JH. Sildenafil use in congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 2009; 94 (6) F467
    PubMedGoogle Scholar
  • 93 De Luca D, Zecca E, Vento G, De Carolis MP, Romagnoli C. Transient effect of epoprostenol and sildenafil combined with iNO for pulmonary hypertension in congenital diaphragmatic hernia. Paediatr Anaesth 2006; 16 (5) 597-598
    CrossrefPubMedGoogle Scholar
  • 94 Filan PM, McDougall PN, Shekerdemian LS. Combination pharmacotherapy for severe neonatal pulmonary hypertension. J Paediatr Child Health 2006; 42 (4) 219-220
    CrossrefPubMedGoogle Scholar
  • 95 Keller RL, Moore P, Teitel D, Hawgood S, McQuitty J, Fineman JR. Abnormal vascular tone in infants and children with lung hypoplasia: Findings from cardiac catheterization and the response to chronic therapy. Pediatr Crit Care Med 2006; 7 (6) 589-594
    CrossrefPubMedGoogle Scholar
  • 96 Ahsman MJ, Witjes BC, Wildschut ED , et al. Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube. Arch Dis Child Fetal Neonatal Ed 2010; 95 (2) F109-F114
    CrossrefPubMedGoogle Scholar
  • 97 Luong C, Rey-Perra J, Vadivel A , et al. Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia. Circulation 2011; 123 (19) 2120-2131
    CrossrefPubMedGoogle Scholar
  • 98 McNamara PJ, Laique F, Muang-In S, Whyte HE. Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. J Crit Care 2006; 21 (2) 217-222
    CrossrefPubMedGoogle Scholar
  • 99 Bassler D, Kreutzer K, McNamara P, Kirpalani H. Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev 2010; (11) CD007802
    PubMedGoogle Scholar
  • 100 Patel N. Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients. Neonatology 2012; 102 (2) 130-136
    CrossrefPubMedGoogle Scholar
  • 101 De Luca D, Zecca E, Piastra M, Romagnoli C. Iloprost as 'rescue' therapy for pulmonary hypertension of the neonate. Paediatr Anaesth 2007; 17 (4) 394-395
    Google Scholar
  • 102 Ehlen M, Wiebe B. Iloprost in persistent pulmonary hypertension of the newborn. Cardiol Young 2003; 13 (4) 361-363
    Google Scholar
  • 103 Inamura N, Kubota A, Nakajima T , et al. A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 2005; 40 (8) 1315-1319
    CrossrefPubMedGoogle Scholar
  • 104 Konduri GG. New approaches for persistent pulmonary hypertension of newborn. Clin Perinatol 2004; 31 (3) 591-611
    CrossrefPubMedGoogle Scholar
  • 105 Sun YJ, Xiong CM, Shan GL , et al; Iloprost Therapy on Pulmonary Hypertension Study Group. Inhaled low-dose iloprost for pulmonary hypertension: a prospective, multicenter, open-label study. Clin Cardiol 2012; 35 (6) 365-370
    CrossrefPubMedGoogle Scholar
  • 106 Hill LL, Pearl RG. Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension. J Appl Physiol 1999; 86 (4) 1160-1164
    PubMedGoogle Scholar
  • 107 Hoeper MM, Galiè N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med 2002; 165 (9) 1209-1216
    CrossrefPubMedGoogle Scholar
  • 108 Bos AP, Tibboel D, Koot VC, Hazebroek FW, Molenaar JC. Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy. J Pediatr Surg 1993; 28 (11) 1463-1465
    CrossrefPubMedGoogle Scholar
  • 109 Mulligan C, Beghetti M. Inhaled iloprost for the control of acute pulmonary hypertension in children: a systematic review. Pediatr Crit Care Med 2011; 13 (4) 472-480
    PubMedGoogle Scholar
  • 110 Mohseni-Bod H, Bohn D. Pulmonary hypertension in congenital diaphragmatic hernia. Semin Pediatr Surg 2007; 16 (2) 126-133
    CrossrefPubMedGoogle Scholar
  • 111 Shiyanagi S, Okazaki T, Shoji H , et al. Management of pulmonary hypertension in congenital diaphragmatic hernia: nitric oxide with prostaglandin-E1 versus nitric oxide alone. Pediatr Surg Int 2008; 24 (10) 1101-1104
    CrossrefPubMedGoogle Scholar
  • 112 Nakwan N, Choksuchat D, Saksawad R, Thammachote P, Nakwan N. Successful treatment of persistent pulmonary hypertension of the newborn with bosentan. Acta Paediatr 2009; 98 (10) 1683-1685
    CrossrefPubMedGoogle Scholar
  • 113 Souza R, Sitbon O, Parent F, Simonneau G, Humbert M. Long term imatinib treatment in pulmonary arterial hypertension. Thorax 2006; 61 (8) 736
    PubMedGoogle Scholar
  • 114 Ghofrani HA, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 2005; 353 (13) 1412-1413
    CrossrefPubMedGoogle Scholar
  • 115 Mathew R. PDGF receptor blocker for pulmonary hypertension: a new agent in therapeutic arsenal. Expert Opin Investig Drugs 2012; 21 (2) 139-142
    CrossrefPubMedGoogle Scholar
  • 116 ten Freyhaus H, Dumitrescu D, Berghausen E, Vantler M, Caglayan E, Rosenkranz S. Imatinib mesylate for the treatment of pulmonary arterial hypertension. Expert Opin Investig Drugs 2012; 21 (1) 119-134
    CrossrefPubMedGoogle Scholar
  • 117 Abe K, Toba M, Alzoubi A , et al. Tyrosine kinase inhibitors are potent acute pulmonary vasodilators in rats. Am J Respir Cell Mol Biol 2011; 45 (4) 804-808
    CrossrefPubMedGoogle Scholar
  • 118 Frenckner B, Broomé M, Lindström M, Radell P. Platelet-derived growth factor inhibition—a new treatment of pulmonary hypertension in congenital diaphragmatic hernia?. J Pediatr Surg 2008; 43 (10) 1928-1931
    CrossrefPubMedGoogle Scholar
  • 119 Chang YT, Ringman Uggla A, Osterholm C , et al. Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol 2012; 302 (11) L1159-L1166
    CrossrefPubMedGoogle Scholar
  • 120 Langham Jr MR, Kays DW, Beierle EA , et al. Twenty years of progress in congenital diaphragmatic hernia at the University of Florida. Am Surg 2003; 69 (1) 45-52
    PubMedGoogle Scholar
  • 121 Van Meurs KP, Newman KD, Anderson KD, Short BL. Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. J Pediatr 1990; 117 (6) 954-960
    PubMedGoogle Scholar
  • 122 Morini F, Goldman A, Pierro A. Extracorporeal membrane oxygenation in infants with congenital diaphragmatic hernia: a systematic review of the evidence. Eur J Pediatr Surg 2006; 16 (6) 385-391
    Article in Thieme ConnectPubMedGoogle Scholar
  • 123 Mugford M, Elbourne D, Field D. Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants. Cochrane Database Syst Rev 2008; (3) CD001340
    PubMedGoogle Scholar
  • 124 Wildschut ED, Ahsman MJ, Houmes RJ , et al. Pharmacotherapy in neonatal and pediatric extracorporeal membrane oxygenation (ECMO). Curr Drug Metab 2012; 13 (6) 767-777
    CrossrefPubMedGoogle Scholar