Skip to main content
Erschienen in: Pediatric Cardiology 6/2015

01.08.2015 | Original Article

Sildenafil for the Treatment of Pulmonary Arterial Hypertension in Infants with Bronchopulmonary Dysplasia

verfasst von: M. N. Trottier-Boucher, A. Lapointe, J. Malo, A. Fournier, M. J. Raboisson, B. Martin, A. Moussa

Erschienen in: Pediatric Cardiology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

Sildenafil, a phosphodiesterase-5 inhibitor, is a controversial treatment option for pulmonary arterial hypertension (PAH), a significant complication of bronchopulmonary dysplasia (BPD). The objective of this study was to evaluate the use of sildenafil in infants with PAH secondary to BPD. This was a retrospective review of medical records of all premature infants with PAH associated with BPD treated with sildenafil between January 2009 and May 2013 in a level 3 neonatal intensive care unit. The primary outcomes were clinical response (20 % decreases in respiratory support score or oxygen requirements) and echocardiographic response (20 % decrease in tricuspid regurgitation gradient or change of at least 1° of septal flattening). Twenty-three infants were included in the study. Significant echocardiographic and clinical responses were, respectively, observed in 71 and 35 % of cases. Most clinical responses were observed in the first 48 h of treatment, and the median time to an echocardiographic response was of 19 days. The median dose of sildenafil used was 4.4 mg/kg/day, with a median time to reach the maximum dose of 9 days. Transient hypotension was the primary reported side effect, and it was observed in 44 % of our study population. Sildenafil treatment in patients with PAH secondary to BPD was associated with an echocardiographic improvement in the majority of patients, whereas clinical improvement was observed in a minority of patients. Many infants presented with transient hypotension during the course of the treatment. Further prospective studies are required to better assess safety and efficacy of this treatment in this population.
Literatur
1.
Zurück zum Zitat Ahsman MJ, Witjes BC, Wildschut ED, Sluiter I, Vulto AG, Tibboel D, Mathot RA (2010) Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube. Arch Dis Child Fetal Neonatal Ed 95(2):F109–F114. doi:10.1136/adc.2009.168336 PubMedCrossRef Ahsman MJ, Witjes BC, Wildschut ED, Sluiter I, Vulto AG, Tibboel D, Mathot RA (2010) Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube. Arch Dis Child Fetal Neonatal Ed 95(2):F109–F114. doi:10.​1136/​adc.​2009.​168336 PubMedCrossRef
3.
Zurück zum Zitat Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A (2009) Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54(1 Suppl):S55–S66. doi:10.1016/j.jacc.2009.04.011 PubMedCrossRef Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A (2009) Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54(1 Suppl):S55–S66. doi:10.​1016/​j.​jacc.​2009.​04.​011 PubMedCrossRef
4.
Zurück zum Zitat Baquero H, Soliz A, Neira F, Venegas ME, Sola A (2006) Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 117(4):1077–1083. doi:10.1542/peds.2005-0523 PubMedCrossRef Baquero H, Soliz A, Neira F, Venegas ME, Sola A (2006) Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 117(4):1077–1083. doi:10.​1542/​peds.​2005-0523 PubMedCrossRef
5.
Zurück zum Zitat Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K (2005) Validation of the national institutes of health consensus definition of bronchopulmonary dysplasia. Pediatrics 116(6):1353–1360. doi:10.1542/peds.2005-0249 PubMedCrossRef Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K (2005) Validation of the national institutes of health consensus definition of bronchopulmonary dysplasia. Pediatrics 116(6):1353–1360. doi:10.​1542/​peds.​2005-0249 PubMedCrossRef
6.
Zurück zum Zitat Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, Bauer CR, Donovan EF, Korones SB, Laptook AR, Lemons JA, Oh W, Papile LA, Shankaran S, Stevenson DK, Tyson JE, Poole WK (2007) Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 196(2):147. doi:10.1016/j.ajog.2006.09.014 e141–148PubMedCrossRef Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, Bauer CR, Donovan EF, Korones SB, Laptook AR, Lemons JA, Oh W, Papile LA, Shankaran S, Stevenson DK, Tyson JE, Poole WK (2007) Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 196(2):147. doi:10.​1016/​j.​ajog.​2006.​09.​014 e141–148PubMedCrossRef
8.
Zurück zum Zitat Herrera TR, Concha GP, Holberto CJ, Loera GR, Rodríguez BI (2006) Oral sildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns. Rev Mex Pediatr 74(4):159–163 Herrera TR, Concha GP, Holberto CJ, Loera GR, Rodríguez BI (2006) Oral sildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns. Rev Mex Pediatr 74(4):159–163
10.
Zurück zum Zitat Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP (2007) Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 120(6):1260–1269. doi:10.1542/peds.2007-0971 PubMedCrossRef Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP (2007) Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 120(6):1260–1269. doi:10.​1542/​peds.​2007-0971 PubMedCrossRef
11.
Zurück zum Zitat Khorana M, Yookaseam T, Layangool T, Kanjanapattanakul W, Paradeevisut H (2011) Outcome of oral sildenafil therapy on persistent pulmonary hypertension of the newborn at Queen Sirikit National Institute of Child Health. J Med Assoc Thai 94(Suppl 3):64–73 Khorana M, Yookaseam T, Layangool T, Kanjanapattanakul W, Paradeevisut H (2011) Outcome of oral sildenafil therapy on persistent pulmonary hypertension of the newborn at Queen Sirikit National Institute of Child Health. J Med Assoc Thai 94(Suppl 3):64–73
12.
Zurück zum Zitat Kim DH, Kim HS, Choi CW, Kim EK, Kim BI, Choi JH (2012) Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology 101(1):40–46. doi:10.1159/000327891 PubMedCrossRef Kim DH, Kim HS, Choi CW, Kim EK, Kim BI, Choi JH (2012) Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology 101(1):40–46. doi:10.​1159/​000327891 PubMedCrossRef
13.
Zurück zum Zitat Limjoco J, Paquette L, Ramanathan R, Seri I, Friedlich P (2013) Changes in mean arterial blood pressure during sildenafil use in neonates with meconium aspiration syndrome or sepsis. Am J Ther. doi:10.1097/MJT.0b013e31826fc4ec Limjoco J, Paquette L, Ramanathan R, Seri I, Friedlich P (2013) Changes in mean arterial blood pressure during sildenafil use in neonates with meconium aspiration syndrome or sepsis. Am J Ther. doi:10.​1097/​MJT.​0b013e31826fc4ec​
14.
Zurück zum Zitat Marsh CS, Marden B, Newsom R (2004) Severe retinopathy of prematurity (ROP) in a premature baby treated with sildenafil acetate (Viagra) for pulmonary hypertension. Br J Ophthalmol 88(2):306–307PubMedCentralPubMedCrossRef Marsh CS, Marden B, Newsom R (2004) Severe retinopathy of prematurity (ROP) in a premature baby treated with sildenafil acetate (Viagra) for pulmonary hypertension. Br J Ophthalmol 88(2):306–307PubMedCentralPubMedCrossRef
15.
18.
Zurück zum Zitat Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD, Poindexter BB, Ingram DA, Abman SH (2015) Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 191(1):87–95. doi:10.1164/rccm.201409-1594OC PubMedCrossRef Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD, Poindexter BB, Ingram DA, Abman SH (2015) Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 191(1):87–95. doi:10.​1164/​rccm.​201409-1594OC PubMedCrossRef
19.
Zurück zum Zitat Nyp M, Sandritter T, Poppinga N, Simon C, Truog WE (2012) Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits? J Perinatol Off J Calif Perinat Assoc 32(1):64–69. doi:10.1038/jp.2011.131 CrossRef Nyp M, Sandritter T, Poppinga N, Simon C, Truog WE (2012) Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits? J Perinatol Off J Calif Perinat Assoc 32(1):64–69. doi:10.​1038/​jp.​2011.​131 CrossRef
20.
Zurück zum Zitat Patel N, Mills JF, Cheung MM (2009) Assessment of right ventricular function using tissue Doppler imaging in infants with pulmonary hypertension. Neonatology 96(3):193–199. discussion 200-192. doi:10.1159/000215585 Patel N, Mills JF, Cheung MM (2009) Assessment of right ventricular function using tissue Doppler imaging in infants with pulmonary hypertension. Neonatology 96(3):193–199. discussion 200-192. doi:10.​1159/​000215585
21.
Zurück zum Zitat Slaughter JL, Pakrashi T, Jones DE, South AP, Shah TA (2011) Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation. J Perinatol 31(10):635–640. doi:10.1038/jp.2010.213 PubMedCrossRef Slaughter JL, Pakrashi T, Jones DE, South AP, Shah TA (2011) Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation. J Perinatol 31(10):635–640. doi:10.​1038/​jp.​2010.​213 PubMedCrossRef
24.
Zurück zum Zitat Vargas-Origel A, Gomez-Rodriguez G, Aldana-Valenzuela C, Vela-Huerta MM, Alarcon-Santos SB, Amador-Licona N (2010) The use of sildenafil in persistent pulmonary hypertension of the newborn. Am J Perinatol 27(3):225–230. doi:10.1055/s-0029-1239496 PubMedCrossRef Vargas-Origel A, Gomez-Rodriguez G, Aldana-Valenzuela C, Vela-Huerta MM, Alarcon-Santos SB, Amador-Licona N (2010) The use of sildenafil in persistent pulmonary hypertension of the newborn. Am J Perinatol 27(3):225–230. doi:10.​1055/​s-0029-1239496 PubMedCrossRef
Metadaten
Titel
Sildenafil for the Treatment of Pulmonary Arterial Hypertension in Infants with Bronchopulmonary Dysplasia
verfasst von
M. N. Trottier-Boucher
A. Lapointe
J. Malo
A. Fournier
M. J. Raboisson
B. Martin
A. Moussa
Publikationsdatum
01.08.2015
Verlag
Springer US
Erschienen in
Pediatric Cardiology / Ausgabe 6/2015
Print ISSN: 0172-0643
Elektronische ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-015-1154-0

Weitere Artikel der Ausgabe 6/2015

Pediatric Cardiology 6/2015 Zur Ausgabe

Letter To The Editor

To the Editor

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.