J Med Assoc Thai 2011; 94 (8):64

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Outcome of Oral Sildenafil Therapy on Persistent Pulmonary Hypertension of the Newborn at Queen Sirikit National Institute of Child Health
Khorana M Mail, Yookaseam T , Layangool T , Kanjanapattanakul W , Paradeevisut H

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.

Material and Method: 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 > 36 weeks gestational age who were
diagnosed as PPHN by echocardiogram and had an oxygenation index > 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.

Conclusion: 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.

Keywords: Persistent pulmonary hypertension, Sildenafil, Oxygenation index

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