title: Outcome of oral sildenafil therapy on persistent pulmonary hypertension of the newborn at Queen Sirikit National Institute of Child Health.
abstract: BACKGROUND
  Persistent pulmonary hypertension of the newborn (PPHN) is a common problem in the neonates with a high mortality rate. The prevalence ranges from 0.38-0.99 per 1,000 live births at Queen Sirikit National Institute of Child Health. The survival rate has improved after the advent of high-frequency ventilation and inhaled nitric oxide. However, inhaled nitric oxide is expensive and unavailable in most neonatal centers in Thailand. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance and hence may play a role in the treatment of PPHN.
  
  
  OBJECTIVE
  To evaluate effectiveness and short-term side effects of oral sildenafil for infants > 36 weeks gestational age who have PPHN.
  
  
  METHODS
  The present study was conducted between January 2006 and December 2008 in the neonatal intensive care unit (NICU) at Queen Sirikit National Institute of Child Health. All infants > or = 36 weeks gestational age who were diagnosed as PPHN by echocardiogram and had an oxygenation index > or = 20 were included in the study. Oral sildenafil was given as per study protocol with a starting dose of 0.25-0.5 mg/kg/dose. Oxygenation index (OI), oxygen saturations (SpO2), alveolar arterial oxygen gradient (A-aDO2) and mean arterial blood pressure (MAP) were monitored serially.
  
  
  RESULTS
  A total of 40 infants were diagnosed with PPHN during this period. Eleven infants were included in the present study. The initial median OI was 31.95 (24.25-48.25). All infants received standard therapy with mechanical ventilation, sedation and inotropic drugs. OI decreased 4.6% from base line after the first hour of starting oral sildenafil and progressively decreased by 13%, 27%, 37%, 41% and 90% at 2, 4, 6, 12 and 24 hours respectively. Oral sildenafil was discontinued in one infant. It was combined with inhaled iloprost in 2 infants due to systemic hypotension and with inhaled nitric oxide in one infant due to deterioration. One infant died during the present study.
  
  
  CONCLUSIONS
  Oral sildenafil may be effective in improving oxygenation in some infants with persistent pulmonary hypertension of the newborn. Systemic hypotension was a cause for concern in the present study. Further studies are needed to assess the pharmacokinetics, efficacy and long-term side effects of this drug.
authors: Neonatal Division, Department of Pediatrics, Queen Sirikit National Institute of Child Health, College of Medicine, Rangsit University, Bangkok, Thailand. meerambbs@yahoo.com
authors: Meera
authors: M
authors: Khorana
authors: Thanatda
authors: T
authors: Yookaseam
authors: Thanarat
authors: T
authors: Layangool
authors: Wiboon
authors: W
authors: Kanjanapattanakul
authors: Hathaitip
authors: H
authors: Paradeevisut
mesh_terms: D000284:Administration, Oral; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007231:Infant, Newborn; D008297:Male; D010100:Oxygen / Q000097:blood*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D010100:Oxygen