Effects of Long-Term Sildenafil Treatment for Pulmonary Hypertension in Infants with Chronic Lung Disease

Abstract

Objective-To determine the clinical course and outcomes of infants with chronic lung disease (CLD) and pulmonary hypertension (PH) who received prolonged sildenafil therapy.Study design-Retrospective review of 25 patients < 2 years of age with CLD in whom sildenafil was initiated for the treatment of PH while hospitalized from January 2004 -October 2007. Hemodynamic improvement was defined by a 20% decrease in the ratio of pulmonary to systemic systolic arterial pressure or improvement in the degree of ventricular septal flattening by serial echocardiograms.Results-Chronic sildenafil therapy (dose range: 1.5-8 mg/kg/d) was initiated at a median of 171 days of age (range: 14-673) for a median duration of 241 days (range: 28-950). Twenty-two patients (88%) achieved hemodynamic improvement after a median treatment duration of 40 days (range: 6-600). Eleven of the 13 patients with interval estimates of systolic pulmonary artery pressure by echocardiogram showed clinically significant reductions in PH. Five patients (20%) died during the follow up period. Adverse events leading to cessation or interruption of therapy occurred in 2 patients, one for recurrent erections, and the other had the medication held briefly due to intestinal pneumatosis.Conclusions-These data suggest that chronic sildenafil therapy is well-tolerated, safe and effective for infants with PH and CLD. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Pulmonary hypertension (PH) complicates the course of chronic lung disease (CLD) in newborns and contributes to late morbidity and mortality during infancy, especially in the setting of bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension of the newborn, (PPHN) and pulmonary hypoplasia. [1][2][3][4][5] Infants with BPD and late PH have a mortality of 52% within 2 years after diagnosis, which is strongly associated with the severity of PH. 5 Although recent advances in vascular biology have led to new therapeutic strategies for the treatment of chronic PH, few studies have investigated the efficacy of these strategies for infants with CLD. NIH Public AccessInhaled nitric oxide (iNO) has become the standard therapy for PH shortly after birth in term and near-term infants. 6 However, its effectiveness during long-term treatment of PH beyond the immediate neonatal period remains unclear. Although several medications for the chronic treatment of PH have been studied in adults and older children, the utility of these medications in infants, especially with CLD, remains uncertain. Oral calcium channel blocker...

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

“…Estimated right ventricular peak systolic pressure greater than half the systemic systolic blood pressure was considered to be consistent with PH. 1,8 A tricuspid regurgitation jet was measured to calculate estimated right ventricular peak systolic pressure using the Bernoulli equation and then adding the assumed right atrial pressures. 11,12 When a tricuspid regurgitation jet was not visualized, then degree of septal flattening and presence of bidirectional shunting was felt to be consistent with PH.…”

“…Previous data suggest that sildenafil citrate has a rapid onset of action, which is evident in treatment of neonatal persistent pulmonary arterial hypertension. 8,9 FiO 2 requirement and highest capillary pCO 2 within the 24 h before starting, 24 h after starting and 48 h after starting sildenafil citrate were also recorded.…”

“…6,7 Sildenafil citrate has also been used in infants with BPD-associated PH, focusing on long-term treatment and improvement in hemodynamics. 8,9 However, to our knowledge, no reports have described concomitant changes in pulmonary gas exchange at initiation of sildenafil citrate in infants treated for BPD-associated PH. We report a 5-year experience of treating BPD-associated PH with sildenafil citrate.…”

El rol de la hipertensión pulmonar en la displasia broncopulmonar

“…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.…”

Managing Children with Bronchopulmonary Dysplasia

“…Силденафил (код АТХ: G04BE03) используется у детей с БЛД при стойкой ЛГ, рефрактерной к стандарт-ной терапии, особенно при отсутствии возможности проведения ингаляций оксида азота (NO) и экстракорпо-ральной мембранной оксигенации (ранее допускалось применение в режиме off label после получения инфор-мированного согласия родителей, согласия Локального этического и Формулярного комитетов в условиях специ-ализированного стационара, с вариабельностью дозы от 1 до 8 мг/кг в сут) [62][63][64]. Однако, было отмечено, что силденафил увеличивает риск тяжелой ретинопатии недоношенных [65].…”