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Objective:  To evaluate the efficacy and safety of different doses of sildenafil for persistent pulmonary hypertension of the newborn (PPHN) with Bayesian random effects network meta-analysis.    Methods:  We searched Chinese and English databases for randomized controlled trials (RCTs) concerning sildenafil in newborns with persistent pulmonary hypertension from 1998 to December 2020.    Results:  Twenty-two RCTs including over 2131 patients were included. Sildenafil was administered by nasal feeding at 0.3–2 mg/kg every 4–6 h. The network meta-analysis revealed that 1.5 mg/kg of sildenafil led to a significant decrease in pulmonary artery systolic pressure (PASP) compared with 0.3 and 0.6 mg/kg ( p  < 0.05); 1.5 mg/kg was better than 0.3, 0.5, and 1.0 mg/kg at increasing the partial pressure of oxygen (PaO 2 ) ( p  < 0.05); 1.5 mg/kg was better than 0.5, 0.6 and 1.0 mg/kg at reducing the partial pressure of carbon dioxide (PaCO 2 ) ( p  < 0.05); and 1.2 mg/kg was better than 0.3, 0.5 and 1.0 mg/kg at increasing the arterial oxygen saturation (SaO 2 ) ( p  < 0.05). The surface under the cumulative ranking analysis (SUCRA) results showed that 1.5 mg/kg had the best effect in reducing PASP (SUCRA = 92.0%, moderate certainty evidence) and PaCO 2  (91.1%) and increasing PaO 2  (SUCRA = 79.3%, moderate certainty evidence), 2.0 mg/kg had the best effect in increasing SaO 2  (SUCRA = 88.6%, moderate certainty evidence) and total effective rate (SUCRA = 93.5%, low certainty of evidence)). No severe adverse effects were observed with the different doses of sildenafil.    Conclusion:  Different doses of sildenafil can significantly improve PPHN, and 1.5 mg/kg of sildenafil has better clinical efficacy and does not increase the probability of adverse reactions.

frontiers in pharmacology

Clinical Efficacy and Safety of Different Doses of Sildenafil in the Treatment of Persistent Pulmonary Hypertension of the Newborn: A Network Meta-analysis