Titre du document / Document title

Oral sildenafil in infants with persistent pulmonary hypertension of the newborn : A pilot randomized blinded study

Auteur(s) / Author(s)

BAQUERO Hernando ⁽¹⁾ ; SOLIZ Amed ⁽²⁾ ; NEIRA Freddy ⁽¹⁾ ; VENEGAS Maria E. ⁽¹⁾ ; SOLA Augusto ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Division of Neonatology, Universidad del Norte, Barranquilla, Colombia, ETATS-UNIS
⁽²⁾ Division of Neonatology, Miami Children's Hospital, Miami, Florida, ETATS-UNIS
⁽³⁾ Division of Neonatology, Emory University, Atlanta, Georgia, ETATS-UNIS

Résumé / Abstract

BACKGROUND. Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is ∼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. DESIGN. 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 (01) >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 alter 36 hours. RESULTS. Six infants with an 01 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.

Revue / Journal Title

Pediatrics   ISSN 0031-4005   CODEN PEDIAU 

Source / Source

2006, vol. 117, n^o4, pp. 1077-1083 [7 page(s) (article)] (30 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Academy of Pediatrics, Elk Grove Village, IL, ETATS-UNIS  (1948) (Revue)

Mots-clés anglais / English Keywords

Respiratory disease ; Cardiovascular disease ; Enzyme inhibitor ; Human ; Enzyme ; Hydrolases ; Esterases ; Phosphoric diester hydrolases ; Vasodilator agent ; Pediatrics ; Neonatal ; Blind ; Clinical trial ; Pilot ; Randomization ; Newborn ; Infant ; 3',5'-Cyclic-GMP phosphodiesterase ; Sildenafil ; Oral administration ; Pulmonary hypertension ;

Mots-clés français / French Keywords

Inhibiteur phosphodiestérase 5 ; Inhibiteur phosphodiesterase ; Appareil respiratoire pathologie ; Appareil circulatoire pathologie ; Inhibiteur enzyme ; Homme ; Enzyme ; Hydrolases ; Esterases ; Phosphoric diester hydrolases ; Vasodilatateur ; Pédiatrie ; Néonatal ; Aveugle ; Essai clinique ; Pilote ; Randomisation ; Nouveau né ; Nourrisson ; 3',5'-Cyclic-GMP phosphodiesterase ; Sildénafil ; Voie orale ; Hypertension artérielle pulmonaire ;

Mots-clés espagnols / Spanish Keywords

Aparato respiratorio patología ; Aparato circulatorio patología ; Inhibidor enzima ; Hombre ; Enzima ; Hydrolases ; Esterases ; Phosphoric diester hydrolases ; Vasodilatador ; Pediatría ; Neonatal ; Ciego ; Ensayo clínico ; Pilote ; Aleatorización ; Recién nacido ; Lactante ; 3',5'-Cyclic-GMP phosphodiesterase ; Sildenafilo ; Vía oral ; Hipertensión arterial pulmonar ;

Mots-clés d'auteur / Author Keywords

neonatal ; pulmonary hypertension ;

Localisation / Location

INIST-CNRS, Cote INIST : 6967, 35400015675631.0090