• The Journal of pediatrics · Feb 1998

    Randomized Controlled Trial Clinical Trial

    Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock.

    • C A Lindsay, P Barton, S Lawless, L Kitchen, A Zorka, J Garcia, A Kouatli, and B Giroir.
    • Division of Pediatric Critical Care, University of Texas Southwestern Medical Center and Children's Medical Center of Dallas, 75235-9063, USA.
    • J. Pediatr. 1998 Feb 1;132(2):329-34.

    ObjectivesThe objectives of this study were to determine the pharmacokinetics of milrinone lactate in pediatric patients with septic shock and to determine whether a relationship exists between steady-state plasma milrinone concentrations and changes in hemodynamic variables.Study DesignThis was a randomized, double-blind, placebo-controlled, interventional study. In study phase 1 patients were randomized and underwent loading and infusion with milrinone lactate (50 microg/kg, then 0.5 microg/kg/min), and invasive hemodynamic values were determined. Steady-state was determined by obtaining plasma samples at 30, 15, and 0 minutes before the end of the milrinone infusion. Study phase 2 started when milrinone was discontinued by the patient care team. Steady-state was reaffirmed and plasma samples were obtained at 0.5, 1, 2, 4, 6, and 8 hours after the end of the infusion.ResultsThe average plasma concentration at steady-state (Css avg) and total body clearance for phase 1 were 81.3+/-38.6 ng/ml (mean +/- SD) and 0.0106+/-0.0053 L/kg/min, respectively (n = 9). All but two patients underwent reloading with milrinone. In phase 2 Css avg and total body clearance were 65.8+/-42.1 ng/ml and 0.0110+/-0.0096 L/kg/min, respectively (n = 11). The average time of infusion was 51+/-21 hours. Eight patients were evaluated for phase 2 elimination. The mean elimination rate constant was 0.0091+/-0.0061 min(-1) (n = 8). The median half-life was 1.47 hours (range, 0.62 to 10.85 hours). All patients had creatinine clearances greater than 61 ml/min/1.73 m2. The volume of distribution at steady-state was 1.47+/-1.03 L/kg. No correlation existed between age and the elimination rate constant or the volume of distribution at steady-state. All patients achieved at least a 20% change in cardiac index and systemic vascular resistance index while maintaining a Css avg of 35 to 160 ng/ml. No adverse effects were noted. All patients achieved primary hemodynamic end points (cardiac index and systemic vascular resistance index) during the milrinone infusion.ConclusionsLoading doses of 75 microg/kg milrinone lactate and starting infusion rates of 0.75 to 1.0 microg/kg/min for patients with normal renal function should be used; the infusion rate should then be titrated to effect. We recommend that for every increase of 0.25 microg/kg/min, a 25 microg/kg bolus dose be given. Because the median half-life is 1.47 hours, immediate hemodynamic effects may not be seen unless appropriate loading doses and infusion adjustments are made.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

What will the 'Medical Journal of You' look like?

Start your free 21 day trial now.

We guarantee your privacy. Your email address will not be shared.