Efficacy and Safety of Pulmonary Vasodilator and Inodilator Drugs in Congenital Heart Disease Surgery: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Background: Perioperative management of congenital heart disease (CHD) surgery presents a unique challenge due to significant pathophysiological alterations, with pulmonary hypertension contributing substantially to morbidity and mortality. Although pulmonary vasodilators and inodilators are commonly used, evidence of their efficacy and safety remains limited. Objectives: To evaluate the effectiveness and safety of vasodilators and inodilators in pediatric patients undergoing CHD surgery. Design: Systematic review with network meta-analysis. Data Sources: PubMed, CENTRAL, and Embase. Eligibility Criteria: We included single- or double-blind, parallel-group, randomized controlled trials comparing the perioperative use of vasodilators and inodilators in pediatric CHD surgery. We selected only English-language studies. We excluded crossover, non randomized trials and trials comparing the same drugs in all study arms. Results: We included 28 randomized controlled trials involving 3118 patients. Intravenous levosimendan ranked highest in decreasing postoperative mortality, although the effect was not statistically significant. Intravenous sildenafil and inhaled nitric oxide (NO) significantly reduced the duration of mechanical ventilation, and inhaled NO also significantly shortened the length of intensive care unit stay. Inhaled iloprost, NO, and enteral sildenafil reduced mean pulmonary artery pressure. No intervention significantly affected the incidence of acute kidney injury. Conclusions: Vasodilators and inodilators did not significantly decrease perioperative mortality in pediatric CHD. Some agents, such as intravenous sildenafil and inhaled NO, demonstrated modest benefits of questionable clinical significance regarding duration of mechanical ventilation, intensive care unit stay, and pulmonary pressure. The results are limited by small sample sizes, study heterogeneity, variability in standard care, and risk of bias, requiring cautious interpretation. Registration: CRD42024552531.