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Sildenafil therapy in bronchopulmonary dysplasia-associated pulmonary hypertension: a retrospective study of efficacy and safety

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Abstract

Bronchopulmonary dysplasia (BPD) is associated with a high incidence of pulmonary artery hypertension (PAH) and is frequently treated with sildenafil. The objective was to investigate the echocardiographic and clinical efficacy and safety of sildenafil in this setting. The hypothesis was that treatment would result in significant echocardiographic and clinical improvements. This was a retrospective study of the cohort of infants who were born between 2004 and 2012 and administered sildenafil as in-patients for BPD-associated PAH. Medical records and archived echocardiographic data were reviewed. Twenty-two infants fulfilled the inclusion criteria and had a mean (±SD) gestation age and birth weight of 25.6 (±1.3) weeks and 631 (±181) g, respectively. Six (27 %) infants died before discharge (predominantly due to respiratory failure; in three of them, a concomitant viral respiratory infection was thought to be an aggravating factor). Amongst survivors, no mortality was noted up to 1 year follow-up. Significant improvement in echocardiographic markers of pulmonary hypertension was noted in the echocardiogram performed 27.5 days (interquartile range 24, 31) post-initiation of therapy, two thirds showing ≥20 % decline in the right ventricular systolic pressure. Left ventricular fractional shortening did not alter significantly. At initiation, all infants had ‘severe’ BPD. The fraction of inspired oxygen (FiO2) decreased significantly from 0.57 (SE ± 0.05) to 0.42 (SE ± 0.03) (p = 0.02), and no significant alteration was noted over the timeframe in mean pCO2 (64.4 ± 3.3 to 63.2 ± 3.3 mmHg). The number of infants needing endotracheal intubation and mechanical ventilation decreased (from 3 to 1) over the same time. No serious adverse effects were noted.

Conclusion: Sildenafil therapy was associated with a significant improvement in the echocardiographic markers of PAH and a reduction in FiO2. The medication was well tolerated.

What is known:

• Sildenafil is used to treat severe bronchopulmonary dysplasia-associated pulmonary hypertension, and pharmacologic effects make it a suitable drug.

• Improvement in echocardiographic parameters has been shown, though many infants were on additional pulmonary vasodilators.

What is new:

• Pulmonary and systemic echocardiographic parameters improved with sildenafil as the sole pulmonary vasodilator.

• It also highlights accompanying clinical improvements, tolerance, and long-term outcomes.

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Abbreviations

ANZNN:

Australia and New Zealand Neonatal Network

BPD:

Bronchopulmonary dysplasia

CPAP:

Continuous positive airway pressure

cGMP:

Cyclic guanosine monophosphate

FS:

Fractional shortening

iNO:

Inhaled nitric oxide

IQR:

Interquartile

IVS:

Interventricular septal

IUGR:

Intrauterine growth restriction

PAH:

Pulmonary artery hypertension

PVD:

Pulmonary vascular disease

PVR:

Pulmonary vascular resistance

RVETc:

Right ventricular ejection time

RVSP:

Right ventricular systolic pressure

TPV:

Time to peak velocity

TRJVmax:

Tricuspid regurgitation jet velocity

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Conflict of interest

No financial relationship with the organisation that sponsored the research.

Author’s contributions

Kenneth Tan: Conceptualised the study, wrote the first draft. Mohan B. Krishnamurthy: Data collection for the clinical arm of the study, input into editing the manuscript. Josie L. O’Heney: Data collection for the clinical arm of the study, input into editing the manuscript. Eldho Paul: Statistical analysis of data and important intellectual input into the manuscript. Arvind Sehgal: Performed echocardiographic analysis, and important intellectual editing input into the manuscript.

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Authors and Affiliations

  1. Monash Newborn, Monash Children’s Hospital, Melbourne, Australia

    Kenneth Tan, Mohan B. Krishnamurthy, Josie L. O’Heney & Arvind Sehgal

  2. Department of Pediatrics, Monash University, Melbourne, Australia

    Kenneth Tan & Arvind Sehgal

  3. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

    Eldho Paul

  4. Monash Children’s Hospital, Monash University, 246, Clayton Road, Clayton, Melbourne, VIC, 3168, Australia

    Arvind Sehgal

Authors
  1. Kenneth Tan
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  2. Mohan B. Krishnamurthy
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  3. Josie L. O’Heney
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  4. Eldho Paul
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  5. Arvind Sehgal
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Correspondence to Arvind Sehgal.

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Communicated by Patrick Van Reempts

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Tan, K., Krishnamurthy, M.B., O’Heney, J.L. et al. Sildenafil therapy in bronchopulmonary dysplasia-associated pulmonary hypertension: a retrospective study of efficacy and safety. Eur J Pediatr 174, 1109–1115 (2015). https://doi.org/10.1007/s00431-015-2515-7

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  • DOI: https://doi.org/10.1007/s00431-015-2515-7

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