Levosimendan versus milrinone in children undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Background Patients undergoing ventricular septal defect or tetralogy of Fallot correction receive inotropic agents that are often required after corrective surgery to support cardiac function. However, the optimal choice between levosimendan and milrinone remains controversial. Purpose We aimed to conduct a meta-analysis to access the main comparison between the effect and safety of prophylactically administered levosimendan and milrinone about patient’s clinical and laboratory improvement Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing levosimendan and milrinone about patients undergoing ventricular septal defect or tetralogy of Fallot correction. The outcomes analyzed were: cardiac index, cardiac index in 12h, cardiac index in 24h, lactate, lactate in 12h and lactate in 24h. Statistical analyses were performed using R software version 5.4.1. We assessed mean differences (MD) for continuous outcomes under a random effects model with 95% Confidence Intervals (CI), with a p-value < 0.05 considered for statistical significance. Results We included 4 RCTs, comprising 135 children, of whom 68 (50.3%) received levosimendan. There were no significant differences between groups regarding cardiac index (0.09; 95% CI -0.18 to 0.37; p=0.62; I²=0%; Figure 2.A) and lactate (-0.04; 95% CI -0.18 to 0.10; p=0.22; I²=26%, Figure 1.A). Furthermore, there was no statistically significant difference between the groups in the subgroup analysis for the cardiac index in 12 hours ( -0.01; 95% CI -0.54 to 0.52; p=0.19; I²=41%, Figure 2.B) and 24 hours ( 0.21; 95% CI -0.25 to 0.66; p=0.47; I²=0%, Figure 2.C) and lactate in 12 hours (0.12; 95% CI -0.13 to 0.37; p=0.79; I²=0%, Figure 1.B) and in 24 hours ( -0.21; 95% CI -0.55 to 0.13; p=0.43; I²=0%, Figure 1.C). Conclusion Our study demonstrated no significant differences between levosimendan and milrinone regarding cardiac index and lactate in children undergoing ventricular septal defect or tetralogy of Fallot correction.