Incidence of milrinone blood levels outside the therapeutic range and their relevance in children after cardiac surgery for congenital heart disease
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To evaluate whether variability in milrinone blood levels (MBL) occurs during administration to critically ill children after surgical repair of congenital heart disease, and the clinical relevance of this variability.
Prospective cohort study conducted in the pediatric intensive care unit of a tertiary care teaching and referral hospital. MBL were measured at three time periods after starting milrinone infusion (9–12, 18–24, 40–48 h) and at the end of the infusion. MBL were categorized as within (100–300 ng/ml) or outside the therapeutic range. Low cardiac output syndrome was defined by elevation of either lactate (>2 mmol/l) or arteriovenous oxygen difference (>30 %). Five other clinical outcomes were evaluated. Regression analyses evaluated the relationships between MBL and outcomes.
Sixty-three patients were included with a total of 220 MBL. Quantification of MBL was by high-performance liquid chromatography. Overall, 114 (52 %) MBL were outside the therapeutic range: 78 (36 %) subtherapeutic, and 36 (16 %) supratherapeutic. Repeated-measures analysis found a significant association between supratherapeutic MBL and low cardiac output syndrome (p = 0.02), and supratherapeutic MBL were associated with arterial–central venous oxygen saturation difference >30 % at time 3 (p = 0.007).
In this cohort, nontherapeutic MBL were common. Further investigation of milrinone dosing recommendations may improve the postoperative outcomes of children.
KeywordsMilrinone Congenital heart disease Child Critical care Pharmacology
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