The effect of sildenafil on evolving bronchopulmonary dysplasia in extremely preterm infants: a randomised controlled pilot study

König, Kai; Barfield, Charles; Guy, Katelyn J.; Drew, Sandra M.; Andersen, Chad

doi:10.3109/14767058.2013.818650

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…In a pilot RCT of 20 infants, four weeks of oral sildenafil solution (3mg/kg/day) was compared to placebo commenced on day seven in mechanically ventilated infants of less than 28 weeks of gestational age. There was no statistically significant difference in BPD at 36 weeks PCA, but a non significant trend for the sildenafil treated group to require more hours of mechanical ventilation and postnatal steroid treatment and they also had a higher respiratory-related mortality [111].…”

Section: Sildenafilmentioning

confidence: 75%

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

Ling

Greenough

2017

Expert Opinion on Orphan Drugs

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Introduction: Bronchopulmonary dysplasia (BPD) is common sequaelae of premature birth.It can be complicated by the development of pulmonary hypertension (PH), which significantly increases mortality. Areas covered: The aim of this review is to evaluate emerging drug therapies for prevention and treatment of BPD and associated PH. These include superoxide dismutase, macrolides, Clara secretary cell protein, -1 protease inhibitors, pentoxifylline, melatonin, inositol, N-acetyl cysteine, allopurinol, cimetidine, pulmonary vasodilators and mesenchymal stem cells (MSC). We have also included discussion on longer standing therapies such as corticosteroids, caffeine and vitamin A.Expert opinion: Corticosteroid administration systemically, but not by inhalation, caffeine and vitamin A reduce BPD. Enhancing endogenous anti-oxidant mechanisms through supplementation with superoxide dismutase or Clara cell secretory protein has yielded encouraging results. Azithromycin, a macrolide used to treat Ureaplasma infection, also has anti-inflammatory properties and has been shown to reduce BPD. Sildenafil reduces the echocardiographic markers of pulmonary hypertension associated with BPD, but has not been shown to prevent BPD. In animal models and a small phase one study MSC administration has resulted in promising results. Appropriately powered studies with long term outcomes are required to assess the efficacy of all these treatments.3

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Section: Sildenafilmentioning

confidence: 75%

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

Ling

Greenough

2017

Expert Opinion on Orphan Drugs

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“…However, in 2014, dose-dependent increases in child mortality led to withdrawal of the FDA recommendation for the use of sildenafil in pediatric PH [17]. Furthermore, limited evidence exists for the use of sildenafil as treatment for PH in patients with BPD, and a recent randomized controlled pilot study found that sildenafil treatment did not improve short-term respiratory outcomes [18]. In our retrospective study, the time to normalization of the TR peak velocity and RV morphology increased among patients treated with sildenafil relative to untreated patients, possibly because patients in the former group had more severe PH.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Outcomes of Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia

Kwon

Kim

An³

et al. 2016

Neonatology

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Background: The long-term cardiovascular outcomes of pulmonary hypertension (PH) in preterm infants with bronchopulmonary dysplasia (BPD) are uncertain. Objectives: The purpose of this study was to assess outcomes of PH in prematurely born children diagnosed with moderate to severe BPD. Methods: We retrospectively reviewed the medical records of patients born before 32 weeks of gestation and diagnosed with moderate to severe BPD from June 2004 to April 2008. Patients were recruited for a cross-sectional study from August to October 2014 and underwent echocardiography. Results: Forty-two children were enrolled. Their mean gestational age and birth weight were 26.2 ± 1.7 weeks and 753.1 ± 172.5 g, respectively. Sixteen patients (38%) were diagnosed with PH at a mean age of 3.3 ± 1.6 months, and the PH improved after a median of 12.3 months (range 0.7-46.6). Cardiovascular function was reassessed at a mean age of 7.7 ± 0.9 years, at which time 1 patient was taking a medication for recurrent PH, and 12 (28.6%) patients exhibited elevated blood pressure. Conventional 2-dimensional and Doppler echocardiography indicated normal ventricular function in all children. However, right ventricular longitudinal strains were decreased in children with previous PH. Conclusions: Subclinical ventricular dysfunction was detectable using sensitive echocardiographic techniques in children with previous BPD-associated PH. Long-term follow-up and meticulous cardiovascular function assessment are required in this population.

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“…As recently reviewed by Wardle et al (), sildenafil may possibly both safe and effective in infants with pulmonary hypertension in BPD, and may improve survival if continued until resolution of pulmonary hypertension. However, sildenafil did not improve short‐term respiratory outcomes in a pilot trial of extremely preterm infants as an attempt to prevent BPD (Konig et al, ), suggesting earlier use may not be beneficial. Mourani et al () did a retrospective review of 25 infants with BPD and pulmonary hypertension who received sildenafil, initiated at a median of 171 days (range, 14–673 days) for a median duration of 241 days (range, 28–940 days).…”

Section: Managementmentioning

confidence: 99%

Pulmonary hypertension in bronchopulmonary dysplasia

Ambalavanan

Mourani²

2014

Birth Defects Research

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Pulmonary hypertension is common in bronchopulmonary dysplasia and is associated with increased mortality and morbidity. This pulmonary hypertension is due to abnormal microvascular development and pulmonary vascular remodeling resulting in reduced cross-sectional area of pulmonary vasculature. The epidemiology, etiology, clinical features, diagnosis, suggested management, and outcomes of pulmonary hypertension in the setting of bronchopulmonary dysplasia are reviewed. In summary, pulmonary hypertension is noted in a fifth of extremely low birth weight infants, primarily those with moderate or severe bronchopulmonary dysplasia, and persists to discharge in many infants. Diagnosis is generally by echocardiography, and some infants require cardiac catheterization to identify associated anatomic cardiac lesions or systemic-pulmonary collaterals, pulmonary venous obstruction or myocardial dysfunction. Serial echocardiography and B-type natriuretic peptide measurement may be useful for following the course of pulmonary hypertension. Currently, there is not much evidence to indicate optimal management approaches, but many clinicians maintain oxygen saturation in the range of 91 to 95%, avoiding hypoxia and hyperoxia, and often provide inhaled nitric oxide, sometimes combined with sildenafil, prostacyclin, or its analogs, and occasionally endothelin-receptor antagonists.

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The effect of sildenafil on evolving bronchopulmonary dysplasia in extremely preterm infants: a randomised controlled pilot study

Abstract: In this pilot study, oral sildenafil treatment did not improve any short-term respiratory outcomes in extremely preterm infants.

Cited by 21 publications

References 29 publications

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

Long-Term Outcomes of Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia

Pulmonary hypertension in bronchopulmonary dysplasia

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