Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension

J Pediatr. 2009 Dec;155(6):841-847.e1. doi: 10.1016/j.jpeds.2009.06.012.


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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infusions, Intravenous
  • Male
  • Persistent Fetal Circulation Syndrome / drug therapy*
  • Persistent Fetal Circulation Syndrome / metabolism
  • Persistent Fetal Circulation Syndrome / physiopathology
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Phosphodiesterase Inhibitors / pharmacokinetics
  • Pilot Projects
  • Piperazines / administration & dosage*
  • Piperazines / pharmacokinetics
  • Pulmonary Gas Exchange
  • Purines / administration & dosage
  • Purines / pharmacokinetics
  • Sildenafil Citrate
  • Sulfones / administration & dosage*
  • Sulfones / pharmacokinetics
  • Treatment Outcome


  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Sildenafil Citrate