Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension.
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).


METHODS
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.
Steinhorn
Robin H
RH
Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children's Memorial Hospital, Chicago, IL 60614, USA. r-steinhorn@northwestern.edu
Kinsella
John P
JP
Pierce
Christine
C
Butrous
Ghazwan
G
Dilleen
Maria
M
Oakes
Michael
M
Wessel
David L
DL
D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011659:Pulmonary Gas Exchange; D011687:Purines / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate