Journal List > Korean J Perinatol > v.24(1) > 1013670

Hwang: Neonatal Pulmonary Hypertension

Abstract

Neonatal pulmonary hypertension is associated with meconium aspiration syndrome, sepsis, asphyxia, respiratory distress syndrome, congenital diaphragmatic hernia, congenital heart disease, or bronchopulmonary dysplasia. Newborns with pulmonary hypertension are at risk of death, chronic lung disease, neurodevelopmental disability, and other complications. Because of the diverse pathophysiology of the underlying disease, the diagnostic evaluation and therapeutic approach are important. This article will review the pathophysiologic background and the current therapeutic options for neonatal pulmonary hypertension.

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Fig. 1
Mechanisms through which current drugs elicit pulmonary vasodilation to treat pulmonary hypertension. AC: Adenylate cyclase; CaM: Calmodulin; CCB: Calcium channel blocker; ET-1: Endothelin-1; MLCK: Myosin light-chain kinase: MLCP: Myosin light-chain phosphatase; NO: Nitric oxide; PDE5: Phosphodiesterase 5; PGI2: Prostcyclin; PLC: Phospholipase C; SsGC1: Soluble guanylate cyclase; SR: Sarcoplasmic reticulum. Quoted from Vasc Health Risk Manag 2009;6:663-71 and Expert Rev Cardiovasc Ther 2010;8:845-62.
kjp-24-1f1.tif
Table 1.
Main Causes of Neonatal Pulmonary Hypertension
Group Description
A Persistent pulmonary hypertension of the newborn (PPHN)
  I. Pulmonary vasoconstriction -eg, meconium aspiration syndrome
  II. Abnormal pulmonary vascular remodelingidiopathic PPHN
  III. Diminished pulmonary vascular bed-pulmonary hypoplasia
B Pulmonary vein stenosis
C Pulmonary hypertension secondary to left heart disease
D Pulmonary hypertension secondary to lung disease and/or hypoxia

Quoted from Arch Dis Child Fetal Neonatal Ed. 2012;97: F223.

Table 2.
Sildenafil in Persistent Pulmonary Hypertension of the Newborn
Author Patients (n) Etiololgy of PPHN Gestational age e Dose/route Outcomes
Steinhorn at al. (2009) 36 MAS, HMD, Sepsis, peumonia, idiopathic >34 weeks and <72 h Loading followed by maintenance dose of 0.07-1.64 mg/kg/hr for 2-7 days; iv. Sustained improvement in oxygenation with higher doses, only one death
Baquero et al . (2006) Sildenafil: 7 Placebo: 6 MAS, HMD > 35.5 week 1-2 mg/kg every 6h; max. 8 dose; oral Sildenafil: one death Placebo: five deaths
Herrea et al. (2006) Sildenafil: 13 Placebo: 11 Not clear Term 2 mg/kg/dose every 6h for 72h; oral ↑Oxygenation (P<0.01)
Vargas-Origel et al. (2010) Sildenafil: 31 Placebo: 20 Not clear Term 3 mg/kg every 6h; oral Sildenafil: two deaths Placebo: eight deaths (P<0.01)
Soliz et al. (2009) Sildenafil: 29 Placebo: 20 Not clear Full term 2 mg/kg every 6h; oral ↑Oxygenation; ↓mortality (P<0.01)
Baquero et al. 2008) 22 Not clear Full term 2 mg/kg every 4-6h; oral 12 neurologically normal at 12-48 months
Noori et al. (2007) 7 CDH Full term 1-2 mg/kg every 12-24h; oral ↑Cardiac output; ↓pulmonary pressure; five survived

Abbreviations: CDH, congenital diaphragmatic hernia; HMD, hyaline membrane disease iv.: Intravenous; MAS, meconium aspiration syndrome; PPHN, persistent pulmonary hypertension of the newborn

Table 3.
Prostacyclin/Iloprost in Persistent Pulmonary Hypertension of the Newborn
Author Gestational age/ Patients (n) Etiololgy of PPHN Dose/route Outcomes
Eronen at al. (1997) 34 weeks to term/8 MAS, HMD, pulmonary hemorrhage, primary PPHN 20 ng/kg/min iv. Increased to max 20 ng/kg/min Survived: 8
Hougland et al. (2005) 38 weeks/21 Not clear 4-14 ng/kg/min iv.; 12 days Survived: 55%
Mangones et al. (2006) 25, 34, 36 and 40 weeks /4 Sepsis, ACD, Pneumonia, BPD 2-10 ng/kg/min iv. Oxygenation improved in all; Survived: 3
Betremieux et al. (2005) Not clear/17 CDH, HMD, ACD, CCAM, sepsis, BA Up to 20 ng/kg/min iv. Survived: 10
Eifinger et al .(2008) 23-25 weeks/4 PPROM 2μ/kg inhalation Improved oxygenation; reduced PPHN on echocardiogram
Kelly et al. (2002) Term/4 Sepsis: 3 ACD 40 ng/kg/min; nebulization for 7-18 days Improved oxygenation; pulmonary pressure decreased; all survived
De Jaegere et al. (1998) 26-33 weeks/4 HMD/Sepsis 50 ng/kg nebulization Improved oxygenation
Histol et al. (2002) 28-31 weeks/3 Hypoplastic lungs Not clear; inhalation Improved oxygenation; survived: 2

Abbreviations: CDH, congenital diaphragmatic hernia; HMD, hyaline membrane disease iv.: Intravenous; MAS, meconium aspiration syndrome; PPHN, persistent pulmonary hypertension of the newborn; ACD, alveolar-capillary dysplasia; BA, birth asphyxia; BPD, bronchopulmonary dysplasia; CCAM, congenital cystic adenomatoid malformation; PPROM, preterm premature rupture of membranes

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