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

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.