Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease

TLDR

Low cardiac output syndrome occurs in up to 25 % of neonates and young children after cardiac surgery, driving postoperative morbidity and mortality. This study assessed whether prophylactic milrinone improves safety and efficacy in pediatric patients at high risk for LCOS. In a double‑blind, placebo‑controlled trial, patients received either low‑dose (25 µg/kg bolus + 0.25 µg/kg/min infusion) or high‑dose (75 µg/kg bolus + 0.75 µg/kg/min infusion) milrinone for 35 h, with death or LCOS as the composite endpoint evaluated up to 30 days. High‑dose milrinone lowered the risk of LCOS by 55 % (64 % in protocol‑compliant patients) and by 48 % through the final visit, with only two deaths occurring after drug infusion, demonstrating a significant reduction in LCOS incidence.

Abstract

Background— Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. Methods and Results— The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25-μg/kg bolus over 60 minutes followed by a 0.25-μg/kg per min infusion for 35 hours; high dose, 75-μg/kg bolus followed by a 0.75-μg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% ( P =0.023) in 238 treated patients and 64% ( P =0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% ( P =0.049). Conclusions— The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.