Advances in Neonatal Pulmonary Hypertension

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a surprisingly common event in the neonatal intensive care unit, and affects both term and preterm infants. Recent studies have begun to elucidate the maternal, fetal and genetic risk factors that trigger PPHN. There have been numerous therapeutic advances over the last decade. It is now appreciated that oxygen supplementation, particularly for the goal of pulmonary vasodilation, needs to be approached as a therapy that has risks and benefits. Administration of surfactant or inhaled nitric oxide (iNO) therapy at a lower acuity of illness can decrease the risk of extracorporeal membrane oxygenation/death, progression of disease and duration of hospital stay. Milrinone may have specific benefits as an ‘inodilator', as prolonged exposure to iNO plus oxygen may activate phosphodiesterase (PDE) 3A. Additionally, sildenafil and hydrocortisone may benefit infants exposed to hyperoxia and oxidative stress. Continued investigation is likely to reveal new therapies such as citrulline and cinaciguat that will enhance NO synthase and soluble guanylate cyclase function. Continued laboratory and clinical investigation will be needed to optimize treatment and improve outcomes.

Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension

“…Vasopressin improved P a O 2 in PHC. These results are consistent with previous reports showing improved oxygenation in PH in infants with congenital heart disease 38,39 and in adults undergoing cardiac surgery. 13 Vasopressin also improved oxygenation more than epinephrine did in a postresuscitation model, because of a lower ventilation-perfusion mismatch.…”

Continuous intravenous sildenafil as an early treatment in neonates with congenital diaphragmatic hernia

“…Although the improved oxygenation is most likely caused by sildenafil treatment, we cannot deny that increased vasopressor support might have beneficially effect oxygenation and PH status in our cohort . The inclusion criteria used in our study were in accordance with previously published studies . However, these criteria might be too liberal and bear the risk of overtreatment.…”

Análogos de prostaglandinas I2 (epoprostenol y treprostinil) para el tratamiento de la hipertensión pulmonar refractaria secundaria a displasia broncopulmonar en un lactante

“…En relación con el tratamiento farmacológico, el óxido nítrico inhalado y el sildenafilo son los fármacos más usados; ambos son eficaces y seguros en niños pretérmino, según los datos disponibles. 5,6 En los adultos, se han descrito resultados eficaces con el uso del bosentán, antagonista de la endotelina-1, pero la experiencia en los pacientes con hipertensión pulmonar secundaria a la displasia broncopulmonar se limita a series de casos. 7 El epoprostenol es un análogo de las prostanglandinas I2 que activa la adenilato ciclasa e incrementa el adenosín monofosfato cíclico (AMPc) de las células musculares lisas de la arteria pulmonar.…”