AUTHOR=Shu Tingting , Chen Huaqiao , Wang Lu , Wang Wuwan , Feng Panpan , Xiang Rui , Wen Li , Huang Wei 

TITLE=The Efficacy and Safety of Pulmonary Vasodilators in Pediatric Pulmonary Hypertension (PH): A Systematic Review and Meta-analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.668902

DOI=10.3389/fphar.2021.668902

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> We performed a meta-analysis to evaluate the efficacy and safety of pulmonary vasodilators in pediatric pulmonary hypertension (PH) patients.</p><p><bold>Methods:</bold> We searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to May 2020, and conducted a subgroup analysis for pulmonary vasodilators or underlying disease.</p><p><bold>Results:</bold> Fifteen studies with 719 pediatric PH patients were included in the meta-analysis. Adverse events did not differ (<italic>p</italic> = 0.11, <italic>I</italic><sup>2</sup> = 15%) between the pulmonary vasodilators group and the control group, neither in the subgroups. In total, compared with the control group treatment, pulmonary vasodilators significantly decreased the mortality (<italic>p</italic> = 0.002), mean pulmonary artery pressure (mPAP, <italic>p</italic> = 0.02), and mechanical ventilation duration (<italic>p</italic> = 0.03), also improved the oxygenation index (OI, <italic>p</italic> = 0.01). In the persistent pulmonary hypertension of the newborn (PPHN) subgroup, phosphodiesterase type 5 inhibitors (PDE5i) significantly reduced mortality (<italic>p</italic> = 0.03), OI (<italic>p</italic> = 0.007) and mechanical ventilation duration (<italic>p</italic> = 0.004). Administration of endothelin receptor antagonists (ERAs) improved OI (<italic>p</italic> = 0.04) and mechanical ventilation duration (<italic>p</italic> &lt; 0.00001) in PPHN. We also found that in the pediatric pulmonary arterial hypertension (PPAH) subgroup, mPAP was pronouncedly declined with ERAs (<italic>p</italic> = 0.006). Systolic pulmonary artery pressure (sPAP, <italic>p</italic> &lt; 0.0001) and pulmonary arterial/aortic pressure (PA/AO, <italic>p</italic> &lt; 0.00001) were significantly relieved with PDE5i, partial pressure of arterial oxygen (PaO<sub>2</sub>) was improved with prostacyclin in postoperative PH (POPH) subgroup (<italic>p</italic> = 0.001). Compared with the control group, pulmonary vasodilators could significantly decrease PA/AO pressure (<italic>p</italic> &lt; 0.00001) and OI (<italic>p</italic> &lt; 0.00001) in the short-term (duration &lt;7 days) follow-up subgroup, improve mPAP (<italic>p</italic> = 0.03) and PaO<sub>2</sub> (<italic>p</italic> = 0.01) in the mid-term (7–30 days) follow-up subgroup, also decrease mortality, mPAP (<italic>p</italic> = 0.0001), PA/AO pressure (<italic>p</italic> = 0.0007), duration of mechanical ventilation (<italic>p</italic> = 0.004), and ICU stay (<italic>p</italic> &lt; 0.00001) in the long-term follow subgroup (&gt;30 days).</p><p><bold>Conclusion:</bold> Pulmonary vasodilators decrease the mortality in pediatric PH patients, improve the respiratory and hemodynamic parameters, reduce the mechanical ventilation duration.</p>