Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study.
BACKGROUND
Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is approximately 10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance.


OBJECTIVE
Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN.


METHODS
This study was a proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube <30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there was no significant change in OI after 36 hours.


RESULTS
Six infants with an OI of >25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived.


CONCLUSIONS
Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.
Baquero
Hernando
H
Division of Neonatology, Universidad del Norte, Barranquilla, Colombia.
Soliz
Amed
A
Neira
Freddy
F
Venegas
Maria E
ME
Sola
Augusto
A
D000284:Administration, Oral; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010100:Oxygen / Q000097:blood; D010547:Persistent Fetal Circulation Syndrome / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D015996:Survival Rate; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D010100:Oxygen