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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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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

In this cohort, nontherapeutic MBL were common. Further investigation of milrinone dosing recommendations may improve the postoperative outcomes of children.

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Acknowledgments

Financial support was provided by the Department of Pediatrics (University of Alberta) and Pediatric Critical Care Associates.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Pediatrics, University of Alberta, 3A3.07 Stollery Children’s Hospital, 8440-112 Street, Edmonton, AB, T6G 2B7, Canada

    Gonzalo Garcia Guerra & Ari R. Joffe

  2. Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada

    Ambikaipakan Senthilselvan

  3. Division of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada

    Demetrios J. Kutsogiannis

  4. Critical Care Medicine and Pediatrics, University of Toronto School of Public Health, Toronto, Canada

    Christopher S. Parshuram

Authors
  1. Gonzalo Garcia Guerra
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  2. Ari R. Joffe
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  3. Ambikaipakan Senthilselvan
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  4. Demetrios J. Kutsogiannis
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  5. Christopher S. Parshuram
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Corresponding authors

Correspondence to Gonzalo Garcia Guerra or Christopher S. Parshuram.

Appendix

Appendix

See Table 5.

Table 5 Definitions of tachycardia and hypotension used in this study
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Garcia Guerra, G., Joffe, A.R., Senthilselvan, A. et al. Incidence of milrinone blood levels outside the therapeutic range and their relevance in children after cardiac surgery for congenital heart disease. Intensive Care Med 39, 951–957 (2013). https://doi.org/10.1007/s00134-013-2858-3

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  • DOI: https://doi.org/10.1007/s00134-013-2858-3

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