Prophylactic milrinone for the prevention of low cardiac output syndrome and mortality in children undergoing surgery for congenital heart disease

Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents

“…Milrinone is a type 3 phosphodiesterase inhibitor approved by the US Food and Drug Administration (FDA) for up to 48 hours of intravenous (IV) treatment in adults with acute decompensated heart failure . Milrinone is not approved for use in patients under 18 years of age, but is frequently administered off‐label to infants and children for the treatment of pulmonary hypertension, low cardiac output, and shock with vasoconstriction . Phosphodiesterase inhibition by milrinone raises intracellular cyclic adenosine monophosphate levels, which increases intracellular calcium concentrations and promotes contractile protein phosphorylation, resulting in improved systolic cardiac contractility, diastolic cardiac relaxation, and vascular relaxation .…”

“…1 Milrinone is not approved for use in patients under 18 years of age, but is frequently administered off-label to infants and children for the treatment of pulmonary hypertension, low cardiac output, and shock with vasoconstriction. [2][3][4][5] Phosphodiesterase inhibition by milrinone raises intracellular cyclic adenosine monophosphate levels, which increases intracellular calcium concentrations and promotes contractile protein phosphorylation, resulting in improved systolic cardiac contractility, diastolic cardiac relaxation, and vascular relaxation. 6,7 Due to a lack of direct adrenoreceptor stimulation, milrinone does not raise myocardial oxygen consumption, a particularly favorable property in the setting of impaired myocardial oxygen delivery.…”

“…All subjects received IV milrinone at a median infusion rate of 0.5 µg/kg/min (range, 0.1-41 µg/kg/min) for a median duration of 12 hours (range, 0.02-2647 hours). The median number of dose adjustments per pediatric patient, including bolus doses, defined as infusions of ࣘ1 hour duration, or changes in infusion rate, was 2.5 (range,[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Renal function as assessed by serum creatinine and estimated CrCl varied across subjects…”

Micro-RNA-208a, -208b, and -499 as Biomarkers for Myocardial Damage After Cardiac Surgery in Children

“…Many factors are known to contribute to the perioperative myocardial damage that leads to a low cardiac output state and end-organ dysfunction in up to 25% of the operated children (21). The ability to diagnose the affected patient in a timely manner will enable the provision of tailored and more effective treatment.…”

Utilisation du levosimendan chez l’enfant

“…Si dans le groupe des inodilatateurs (dobutamine, enoximone, milrinone, levosimendan), le levosimendan semble donc particulièrement efficace pour le traitement du choc cardiogénique post-cardiotomie, les rares études randomisées ne permettent pas de conclure à une différence d'efficacité par rapport aux autres traitements inotropes [4,24,37,38]. Pour autant, une méta-analyse récente a également échoué à mettre en évidence un effet bénéfique de l'administration prophylactique de la milrinone, pourtant considérée comme traitement inotrope de référence dans le contexte de la chirurgie cardiaque pédiatrique [39]. Ceci s'explique par le très faible nombre d'études randomisées réalisées chez l'enfant (en l'occurrence seulement 5 pour la milrinone, ne différenciant ni les cardiopathies ni les âges).…”