Use of milrinone in critically ill children

Optimal dose adjustment of milrinone in critically ill children is challenging because of conflicting information about the association between dose and outcomes in this age group.

To describe the use of milrinone in critically ill children and to explore associations between milrinone dosing and clinical outcomes, specifically effectiveness and adverse events.

This retrospective cohort study was performed in a consecutive sample of children admitted to a university-affiliated critical care unit (January to June 2004). The relations between milrinone dosing and its effectiveness (based on prevention of low cardiac output syndrome, defined as a difference in oxygen saturation between arterial and mixed venous blood of at least 30% or an increase in serum lactate > 2 mmol/L) and its adverse effects (thrombocytopenia, arrhythmia) were evaluated by logistic regression.

A total of 197 children from 213 admissions (ranging in age from newborn to 18 years) were included in the study. Milrinone was initiated with a median loading dose of 99.2 μg/kg (range 22.1-162.2 μg/kg). The initial loading dose was higher if given in the operating room rather than the Critical Care Unit (median 99.7 versus 51.0 μg/kg; p < 0.001). Subsequent loading doses, for patients who received them, were lower (median 49 μg/kg). Milrinone was infused at a median rate of 0.64 μg/kg per minute (range 0.13-2.08 μg/kg per minute) for a median of 43.1 h. There was no relation between serum creatinine level and the maintenance dose of milrinone (r2 ≤ 0.0335). Low cardiac output syndrome was relatively frequent (166 [77.9%] of the 213 admissions). There was a trend for occurrence of this syndrome in patients with greater average milrinone dose rate (odds ratio [OR] 8.21, 95% confidence interval [CI] 0.98-69.15, p = 0.053) and with longer duration of milrinone therapy (OR 1.01, 95% CI 1.01-1.02, p < 0.05). Adverse events were relatively frequent (thrombocytopenia for 27 admissions [12.7%], arrhythmia for 82 admissions [38.5%]) but were not significantly associated with milrinone dosing.

A retrospective evaluation of milrinone use in critically ill children revealed variable utilization and frequent occurrence of both low cardiac output syndrome and adverse events. Further prospective research is needed to understand the impact of individual pharmacokinetic differences on pharmacodynamic responses, to guide optimal dose adjustment, improve outcomes, and minimize toxic effects.