Efficacy And Safety Of Vasodilators For The Management Of Persistent Pulmonary Hypertension Of The Newborn: A Systematic Review And Network Meta-analysis

Abstract

Background

Persistent pulmonary hypertension of the newborn (PPHN) is a critical condition characterized by elevated pulmonary vascular resistance (PVR) with subsequent right-to-left shunting. PPHN is associated with significant increase in neonatal morbidity and mortality. While inhaled nitric oxide is the primary treatment, alternative pulmonary vasodilators are currently under investigation due to inhaled nitric oxide limitations. Our study aims to compare the efficacy of various vasodilators as a second-line therapy or adjunctive therapy for management of PPHN.

Methods

We conducted a network meta-analysis to analyze nine treatment options, including inhaled nitric oxide, phosphodiesterase inhibitors, and endothelin-1 receptor antagonists. The outcomes analyzed in our study included oxygenation index, length of hospital stay, side effects, treatment failure, and mortality. Statistical analyses were performed using R software with the netmeta package.

Results

We included 12 randomized controlled trials involving 2,911 patients. Milrinone and sildenafil demonstrated statistically significant reduction in thge length of hospital stay in the treatment group when compared to the placebo group, with mean difference (MD) of -6.9 days (95% confidence interval (CI): -12.7 to -1.36) and -6.3 days (95% CI: -12.0 to -0.6), respectively. While surfactant and nitric oxide were the most effective in reducing treatment failure, with statistically significant MDs of -0.734 (95% CI: -1.30; -0.17) and -0.6 (95% CI: -0.81; -0.38) respectively. There were no statistically significant difference among the treatment group when compared to the control group in improving oxygenation index, lowering side effects or improving mortality.

Conclusion

This network meta-analysis provides insights into the comparative efficacy of various pulmonary vasodilators for PPHN management. While some treatment options showed promising results in particular outcomes, further research is needed to confirm these findings and identify optimal strategies for improving neonatal outcomes in PPHN.