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.

Retrospective review of neonates with persistent pulmonary hypertension of the newborn at Charlotte Maxeke Johannesburg Academic Hospital

“…[2] PPHN is associated with a high mortality rate, especially in resource-limited settings. [4] Of the 72 neonates included in this study, 25 (34.7%) did not survive. Similar mortality rates, either directly or indirectly related to PPHN, were reported in previous studies across the world, e.g.…”

“…[2,3] Despite the progress in treating PPHN, it remains a potentially fatal disease, especially in resource-limited settings. [4] The reported overall mortality ranges from 4% to 33% in developed countries [2] and from 25% to 48% in developing countries. [5,6] In South Africa (SA), previous studies reported the incidence of PPHN to be 1.1%, with a mortality rate of 31% at Tygerberg Children's Hospital [7] and 48% at Chris Hani Baragwanath Academic Hospital.…”

Using Simulated Transport Calls to Identify Diversity of Knowledge and Care Plans among the Multidisciplinary Team

“…The management of PPHN is widely varied with the ideal combination and doses of therapeutic agents unknown [11]. The results from the preliminary study looking at variance among disciplines in the preparation and management of a critically ill infant with PPHN show a trend toward alignment of attendings and NNPs.…”

Outcomes of Newborn Infants With Pulmonary Hypertension Treated With Oral Sildenafil

“…Clinical diagnosis of pulmonary hypertension was based on persistent hypoxemia despite ventilation with 100% oxygen, and a difference in oxygen saturation between the upper and lower limbs of ≥ 10% [8], which is usually seen in highrisk term or late preterm infants [9]. Echocardiography criteria for diagnosis of PPHN were based on both qualitative and Neonatal Pulmonary Hypertension Int J Clin Pediatr.…”