Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

Nyp, Michael F.; Sandritter, Tracy; Poppinga, N; Simon, Catherine; Truog, William E.

doi:10.1038/jp.2011.131

Cited by 75 publications

(73 citation statements)

References 19 publications

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“…23,24,28,32,33 However, the absence of long-term safety and efficacy data 34 may have contributed to the fact that the majority (83%) of infants with BPD-PH in this study population did not receive sildenafil. Clinicians seem to reserve sildenafil for a "sicker" subgroup of infants with BPD-PH: those receiving sildenafil were born more prematurely, were more likely to be SGA, had more severe lung disease, and had longer hospitalizations.…”

Section: Discussionmentioning

confidence: 95%

“…Steinhorn et al 28 described improvements in oxygenation status among infants 4 hours after sildenafil administration. Nyp et al 24 showed that, among 21 preterm infants with moderate or severe BPD, sildenafil exposure for a median of 167 days was associated with clinically significant reductions in estimated right ventricular peak systolic pressures. In our cohort, the median duration of sildenafil therapy was 52 days, with marked variation in the duration of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16][17][18][19][20] Early clinical experience indicates that sildenafil treatment may be efficacious for infants with BPD-PH, with evidence suggesting that sildenafil normalizes lung development and may improve outcomes. [21][22][23][24][25] However, practice patterns for sildenafil treatment in infants with BPD-PH have not been fully reported; these patterns include variables associated with exposure, timing of initiation, length of treatment, and interhospital variation in use. Current sildenafil exposure among infants with BPD-PH remains influenced largely by the personal preferences of individual physicians and single-center experiences of safety and efficacy.…”

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confidence: 99%

See 2 more Smart Citations

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Backes

Reagan

Smith

et al. 2016

Hospital Pediatrics

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OBJECTIVE: This study had 2 goals: (1) to identify clinical and demographic characteristics associated with sildenafil exposure for infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH); and (2) to characterize hospital-specific treatment frequency, age at first administration, and length of sildenafil treatment. METHODS: This retrospective cohort study used data from the Pediatric Health Information System to determine variables associated with sildenafil exposure and between-hospital variations in sildenafil utilization patterns. The study included infants with BPD-PH who were discharged between January 1, 2006, and December 31, 2013. RESULTS: Within 36 US pediatric hospitals, 3720 infants were diagnosed with BPD, of whom 598 (16%) also had a diagnosis of PH (BPD-PH). Among infants with BPD-PH, 104 infants (17%) received sildenafil. The odds for sildenafil treatment among infants born between 25 and 26 weeks’ gestational age (GA) and <24 weeks’ GA, respectively, were 2.26 (95% confidence interval [CI]: 1.20–4.24) and 3.21 (95% CI: 1.66–6.21) times those of infants born at 27 to 28 weeks’ GA. Severity of BPD correlated with sildenafil exposure, with adjusted odds ratios (ORs) for moderate BPD (OR: 3.03 [95% CI: 1.03–8.93]) and severe BPD (OR: 7.56 [95% CI: 2.50–22.88]), compared with mild BPD. Greater rates of sildenafil exposure were observed among small for GA neonates (OR: 2.32 [95% CI: 1.21–4.46]). The proportion of infants with BPD-PH exposed to sildenafil varied according to hospital (median: 15%; 25th–75th percentile: 0%–25%), as did the median duration of therapy (52 days; 25th–75th percentile: 28–109 days). CONCLUSIONS: The odds of sildenafil treatment were greatest among the most premature infants with severe forms of BPD. The frequency and duration of sildenafil exposure varied markedly according to institution. Patient-centered trials for infants with BPD-PH are needed to develop evidence-based practices.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

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Reagan

Smith

et al. 2016

Hospital Pediatrics

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“…Alterations of NO-cyclic guanosine monophosphate signaling disrupt lung and pulmonary vascular development in animal models of prematurity and lung injury (12)(13)(14), but these findings have not been successfully translated into therapeutic advances. Vascular agents such as iNO and sildenafil may acutely improve pulmonary artery pressure, but their long-term efficacy remains uncertain and poorly studied (15)(16)(17). A major barrier in conducting larger scale studies of promising therapies has been the identification of appropriate patients for inclusion.…”

Section: Sharpening the Tools Of Detectionmentioning

confidence: 99%

Pulmonary Hypertension in Premature Infants. Sharpening the Tools of Detection

Farrow

Steinhorn

2015

Am J Respir Crit Care Med

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measurements, as well as acceptable measurements in more than 1,000 children aged 5-12 years. A comparison of children living in a range of locations in India with those of Indian heritage who were living in London in the United Kingdom revealed significantly higher FEV 1 and FVC (per z-scores relative to reference values derived from Indian populations) in the London residents. However, when the India-resident children were subgrouped into urban, semiurban, and rural areas of residence, it was discovered that the urban-residing children from India had spirometric measures that were indistinguishable from those measured in the London contingent. In contrast, the rural-residing Indian children had FEV 1 and FVC measures that were 0.9 z-scores lower, and the semiurban Indian group had measures 0.5 z-scores lower, than the India urban and London groups. Assuming that the genetically determined physical characteristics relating predicted lung volumes to height, age, and sex are relatively constant for the general population of India, these results suggest strongly that differences in living conditions among these subpopulations have a significant effect on lung development or lung function. This is useful information, as it identifies a population that could hold clues to mechanisms by which environmental conditions may affect lung development in utero or in early life and that may benefit from interventions to improve lung health.The authors also report that the z-FEV 1 /FVC was not significantly different among the subpopulations, suggesting a restrictive (reduced lung size), rather than obstructive, pattern in the nonurban residents. This needs to be confirmed with a measure of total lung capacity (TLC), which would not be possible for population screening but could be attempted in a representative sample of participants. In persons with normal respiratory systems, the primary determinant of FEV 1 is FVC, the primary determinant of FVC is TLC, and the primary determinant of TLC is thoracic volume, which relates to height and chest dimensions. Thus, the surrogate measures (height, age, sex, ethnic heritage) that are used to compute reference ranges for spirometry mostly function as an estimate of TLC. If the actual TLC is significantly different from the expected TLC, this will affect the z-FEV 1 and z-FVC but will not affect the z-FEV 1 /FVC unless the TLC is altered by a process that also affects airway integrity or lung elastic recoil. The alternative scenario that may cause a proportional decrease of FEV 1 and FVC is premature airway closure during forced expiration (2), although this is unlikely in the absence of chronic respiratory symptoms.The authors employed a multivariate model that included family affluence score, exposure to household tobacco smoke, exposure to indoor biomass smoke, z-body weight, and z-body mass index, but these variables were nearly qualitatively associated with place of residence, so none emerged as strong correlates with the spirometric measures. Specific data regarding maternal to...

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“…Debido a esto último, se debe vigilar la aparición de hipotensión sistémica como efecto adverso a su uso. Con esta droga sólo existen series retrospectivas de menos de 25 pacientes cada una las que en grado variable han mostrado mejoría ecocardiográfica y clínica de su HP 22,23,24,25 . El estudio más completo parece ser el de Trottier-Boucher et al, que muestra una mejoría ecocardiográfica y clínica en 74 y 35% de sus pacientes respectivamente.…”

Section: Terapias Específicasunclassified

El rol de la hipertensión pulmonar en la displasia broncopulmonar

Valenzuela

Moya

Luco

et al. 2017

Rev. chil. pediatr.

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Palabras clave: Displasia broncopulmonar, Hipertensión pulmonar, enfermedad pulmonar crónica, recién nacido prematuro ResumenHace 50 años Northway describió la Displasia Broncopulmonar (DBP), en nacidos de pretérmino expuestos a ventilación mecánica. Desde entonces, ha aumentado la sobrevida de ellos; sin embargo, ha aparecido una "nueva DBP" y la incidencia de esta no ha disminuido. Una de las características de esta patología es la remodelación vascular anómala, que en su expresión más severa se conoce como Hipertensión Pulmonar (HP); con una incidencia de 17%, que es proporcional a la severidad de la DBP (33% en DBP severa); y como un factor de mortalidad (hasta un 48% mortalidad a 2 años con HP por DBP). Debido a esto resulta importante conocer los métodos diagnósticos y alternativas terapéuticas, tema que se discute en esta revisión. Considerando la alta mortalidad de la asociación HP-DBP, adquiere importancia una estrategia de tamizaje en la población de riesgo. El gold standard para el diagnóstico de HP es el cateterismo cardíaco, sin embargo, el ecocardiograma transtorácico es una herramienta útil para el tamizaje y diagnóstico de HP en pacientes displásicos, con mediciones cuantitativas y cambios cualitativos en la evaluación diagnóstica. A nivel sanguíneo el péptido natriurético tipo B (BNP), ha mostrado ser útil en el seguimiento; en cuanto a imágenes, la tomografía computarizada se utiliza en casos severos. En cuanto a las terapias, se han propuesto el óxido nítrico inhalado como vasodilatador pulmonar, los inhibidores de la fosfodiesterasas -sildenafil-, los antagonistas de la endotelina -bosentán-y los análogos de prostaciclinas -iloprost-. Aún no se cuenta con evidencia de alta calidad para su uso, dosis y duración del tratamiento, pero hay variadas experiencias clínicas. Además, es relevante el cuidado interdisciplinario, destacando optimizar la nutrición. El desafío es lograr una prevención efectiva de la DBP y de sus complicaciones. Un protocolo de tamizaje de HP debe asociarse a una estratificación de riesgo y directrices de tratamiento.

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Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

Cited by 75 publications

References 19 publications

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Pulmonary Hypertension in Premature Infants. Sharpening the Tools of Detection

El rol de la hipertensión pulmonar en la displasia broncopulmonar

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