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

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-g/kg bolus over 60 minutes followed by a 0.25-g/kg per min infusion for 35 hours; high dose, 75-g/kg bolus followed by a 0.75-g/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% (Pϭ0.023) in 238 treated patients and 64% (Pϭ0.007) 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% (Pϭ0.049). Conclusions-The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

Early extubation after congenital heart surgery

“…Study of the Neirotti et al (15) showed, as well as our research, that failure to thrive is one of the risk factor of prolonged ventilation [95%CI (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)]. …”

“…Longer CPB time is also repeatedly reported to be associated with prolonged mechanical ventilation following CHD surgery (17).…”

Use of Milrinone to Treat Cardiac Dysfunction in Infants with Pulmonary Hypertension Secondary to Congenital Diaphragmatic Hernia: A Review of Six Patients

“…In these, milrinone has been employed primarily as an inotrope and systemic vasodilator, rather than as a pulmonary vasodilator. Following cardiac surgery, milrinone appears effective in preventing low cardiac output states; however, in the preterm transitional circulation the same benefits were not observed [17,18]. …”

Comparison of early and late intravenous infusion of milrinone in pediatric patients undergoing cardiac surgery

“…The authors concluded that the use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS [15].…”

“…Milrinone is a drug commonly used to support cardiac output after congenital heart surgery in neonates, infants, and children. Pharmacokinetic studies suggest that milrinone clearance is greater and its volume of distribution larger in children than in adults [3,15], but infants appear to have lower milrinone clearance than children [3].…”