Persistent Pulmonary Hypertension of the Newborn: Recent Advances in the Management

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a medical emergency in the neonatal period, which occurs due to failure of normal postnatal transition of fetal circulation. Despite availability of numerous treatment modalities, associated mortality and morbidity remain high. Therefore, awareness of predisposing conditions, and early diagnosis and management may help improving outcome in PPHN. To provide an overview of anatomic and functional anomalies of PPHN, and available treatment options with special focus on recent advances in the diagnosis and management of this potentially lethal illness. MEDLINE, EMBASE, The Cochrane Library, and Google Scholar databases were searched (inception until Nov-2012) using terms persistent pulmonary hypertension of newborn, hypoxemic respiratory failure, nitric oxide, sildenafil, milrinone and prostacyclin without any language restriction. www.clinicaltrials.gov website was searched for relevant ongoing trials. Additionally, manual review of article bibliographies was done for potentially relevant studies. Strategies for the management of PPHN are undergoing metamorphosis. Gentle ventilation and high-frequency ventilation have replaced prior hyperventilation strategy. Currently, iNO is the only FDA-approved selective pulmonary vasodilator for infants with hypoxemic respiratory failure/PPHN; however, it has poor/no response in upto 30% cases. Recent studies have provided evidences for the use of other therapeutic agents such as PDE-inhibitors, magnesium sulphate and prostacyclin analogues. Finally, recent laboratory studies have demonstrated the role of oxidant stress as well as potential use of free radical scavengers for example, superoxide dismutase and catalase in the management of PPHN. Assisted ventilation and pharmacologic manipulation are the mainstays of treatment of PPHN. Limited availability of the gold standard treatment option namely iNO, especially in resource-limited countries, leads to increasing use of alternative therapeutic options such as PDE-inhibitors (sildenafil and milrinone). However, as any single therapy can not be labelled as a magic bullet for PPHN, further clinical trials are required to demonstrate the efficacy and safety of available therapeutic options as well as to develop newer strategies targeted to the underlying pathophysiology.




doi: http://dx.doi.org/10.4021/ijcp79w