Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension

Robin H Steinhorn, John P. Kinsella, Christine Pierce, Ghazwan Butrous, Maria Dilleen, Michael Oakes, David L. Wessel

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Objective To evaluate the safety of intravenous (IV) sildenafil, an inhibitor of cyclic guanosine monophosphate- specific phosphodiesterase, in treating near-term and term newborns with persistent pulmonary hypertension of the newborn (PPHN). Study design This was an open-label, dose-escalation trial in newborns with PPHN and an oxygenation index (OI) > 15. Sildenafil was delivered by continuous IV infusion for at least 48 hours and up to 7 days. Results Five centers enrolled a total of 36 neonates with PPHN at a mean of 34 ± 17 hours of age; 29 of these neonates were already receiving inhaled nitric oxide (iNO). A significant improvement in OI (28.7 to 19.3; P = .0002) was observed after 4 hours of sildenafil infusion in the higher dose cohorts. Thirty-five neonates survived; 1 neonate required extracorporeal membrane oxygenation (ECMO) support. In 4 neonates, sildenafil was stopped due to adverse events. Seven neonates were enrolled before developing the need for iNO. In these neonates, OI improved significantly by 4 hours after initiation of sildenafil infusion (24.6 to 14.7; P = .009); 6 neonates completed treatment without the need for iNO or ECMO. Conclusions IV sildenafil was well tolerated, and acute and sustained improvements in oxygenation were noted in those neonates who received the higher infusion doses.

Original languageEnglish (US)
JournalJournal of Pediatrics
Volume155
Issue number6
DOIs
StatePublished - Dec 2009
Externally publishedYes

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Pulmonary Hypertension
Persistent Fetal Circulation Syndrome
Nitric Oxide
Extracorporeal Membrane Oxygenation
Therapeutics
Cyclic GMP
Phosphoric Diester Hydrolases
Intravenous Infusions
Sildenafil Citrate
Safety

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Steinhorn, R. H., Kinsella, J. P., Pierce, C., Butrous, G., Dilleen, M., Oakes, M., & Wessel, D. L. (2009). Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. Journal of Pediatrics, 155(6). https://doi.org/10.1016/j.jpeds.2009.06.012

Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. / Steinhorn, Robin H; Kinsella, John P.; Pierce, Christine; Butrous, Ghazwan; Dilleen, Maria; Oakes, Michael; Wessel, David L.

In: Journal of Pediatrics, Vol. 155, No. 6, 12.2009.

Research output: Contribution to journalArticle

Steinhorn, RH, Kinsella, JP, Pierce, C, Butrous, G, Dilleen, M, Oakes, M & Wessel, DL 2009, 'Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension', Journal of Pediatrics, vol. 155, no. 6. https://doi.org/10.1016/j.jpeds.2009.06.012
Steinhorn, Robin H ; Kinsella, John P. ; Pierce, Christine ; Butrous, Ghazwan ; Dilleen, Maria ; Oakes, Michael ; Wessel, David L. / Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. In: Journal of Pediatrics. 2009 ; Vol. 155, No. 6.
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