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Sildenafil therapy for neonatal and childhood pulmonary hypertensive vascular disease

Published online by Cambridge University Press:  08 December 2010

Tilman Humpl ,
Janette T. Reyes ,
Simon Erickson ,
Ruth Armano ,
Helen Holtby  and
Ian Adatia
Tilman Humpl
Affiliation:
Hospital for Sick Children, University of Toronto, Toronto, Canada
Janette T. Reyes
Affiliation:
Hospital for Sick Children, University of Toronto, Toronto, Canada
Simon Erickson
Affiliation:
Princess Margaret Hospital, University of Western Australia, Perth, Australia
Ruth Armano
Affiliation:
Cliniques Universitaires de St Luc, Brussels, Belgium
Helen Holtby
Affiliation:
Hospital for Sick Children, University of Toronto, Toronto, Canada
Ian Adatia*
Affiliation:
Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada
*
Correspondence to: Dr I. Adatia, Room 3A1.44, Walter C Mackenzie Health Sciences Center, 8440 112 Street, Edmonton, Alberta T6G 3T7, Canada. Tel: 780 407 3642; Fax: 780 407 3954 E-mails: iadatia@ualberta.ca, ianadatia@me.com
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Abstract

Objectives

We hypothesised that sildenafil would improve hemodynamics in children with pulmonary hypertension and attenuate rebound pulmonary hypertension after inhaled nitric oxide withdrawal.

Patients and methods

We undertook an open-label, single-drug study of sildenafil in patients under 5 years of age with either symptomatic or rebound pulmonary hypertension following inhaled nitric oxide withdrawal.

Results

We recruited 25 patients (median age 180 days, 10–1790) to receive sildenafil. The median right ventricular to systemic systolic blood pressure ratio before sildenafil therapy was 1.0 (0.5–1.4) and decreased to 0.5 (with a range from 0.3 to 1.3; p = 0.0002). In five patients the baseline pulmonary vascular resistance index was 10 (7.1–13.6) Wood units metre square and decreased to 5.8 (2.7–15.6) Wood units metre square (p = 0.04) at 6 months. Ten patients were treated with sildenafil for a median of 34 days (9–499) until resolution of pulmonary artery hypertension and continue to do well. Six patients continued sildenafil therapy for a median of 1002 days (384–1574) with improvement but without resolution of pulmonary hypertension. There was no change in serum creatinine, urea, liver function tests, or platelet count. In 15 patients sildenafil abolished rebound pulmonary artery hypertension following withdrawal of inhaled nitric oxide. Median right ventricular pressure to systemic systolic pressure ratio decreased from 1.0 (0.8–1.4) during nitric oxide withdrawal to 0.4 (0.3–0.8) p = 0.006 after pre-treatment with sildenafil.

Conclusion

In children under 5 years of age with severe pulmonary hypertension, sildenafil therapy resulted in prolonged hemodynamic improvements without adverse effects. Sildenafil attenuated rebound pulmonary hypertension after withdrawal of inhaled nitric oxide.

Keywords

Sildenafilneonatalpulmonary hypertensioncongenital cardiac diseasecongenital diaphragmatic hernia
Type
Original Articles
Information
Cardiology in the Young , Volume 21 , Issue 2 , April 2011 , pp. 187 - 193
Copyright
Copyright © Cambridge University Press 2010

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