Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn

Abstract

Persistent pulmonary hypertension in newborn (PPHN) is a serious and possibly fatal syndrome characterized by sustained foetal elevation of pulmonary vascular resistance at birth. PPHN may manifest secondary to other conditions as meconium aspiration syndrome, infection and congenital diaphragmatic hernia. This MiniReview provides the reader with an overview of current and future treatment options for patients with PPHN without congenital diaphragmatic hernia. The study is based on systematic searches in the databases PubMed and Cochrane Library and registered studies on Clinicaltrials.gov investigating PPHN. Inhaled nitric oxide (iNO) is well documented for treatment of PPHN, but 30% fail to respond to iNO. Other current treatment options could be sildenafil, milrinone, prostaglandin analogues and bosentan. There are several ongoing trials with sildenafil, but evidence is lacking for the other treatments and/or for the combination with iNO. Currently, there is no evidence for effect in PPHN of other treatments, for example tadalafil, macitentan, ambrisentan, riociguat and selexipag used for pulmonary arterial hypertension in adults. Experimental studies in animal models for PPHN suggest effect of a series of approaches including recombinant human superoxide dismutase, L-citrulline, Rho-kinase inhibitors and peroxisome proliferator-activated receptor-γ agonists. We conclude that iNO is the most investigated and the only approved pulmonary vasodilator for infants with PPHN. In the iNO non-responders, sildenafil currently seems to be the best alternative either alone or in combination with iNO. Systematic and larger clinical studies are required for testing the other potential treatments of PPHN.

Infecciones respiratorias virales en pacientes hospitalizados en una unidad de cuidados intensivos neonatales

“…También se encontró que más de la mitad de los pacientes presentó algún grado de hipertensión pulmonar previo a la adquisición de la infección viral. Se plantea que las infecciones respiratorias, así como otras afecciones del recién nacido, producen de forma secundaria aumento de la presión pulmonar, en consecuencia, la hipertensión pulmonar podría acompañar el curso de una infección respiratoria viral y no ser (18) precisamente la causa de éstas .…”

Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches

“…Selexipag, an orally administered prodrug of a PGI2 receptor agonist, has been recently studied, and showing encouraging results, for use in the treatment of PAH in adults (55,82). However, no animal (or human) studies investigating selexipag use in PPHN have been found, although theoretically it may have potential for the treatment of this condition.…”

Inhaled Pulmonary Vasodilators in the Neonatal and Pediatric ICU

“…Data from adult drug trials list the side effects as hypotension, drug tolerance, nausea or vomiting, headache, cough, flushing, and jaw pain. 114 Please see Table 3 for observed adverse events associated with inhaled prostacyclins.…”