Milrinone pharmacokinetics in critically ill children

J. Scott Baird, Henry Michael Ushay, Daniel A. Notterman

Research output: Contribution to journalArticle

Abstract

Introduction: We investigated the pharmacokinetic characteristics of loading and continuous infusion therapy with railrinone in critically ill children, a group in which pharmacokinetic data are limited. Method: Fourteen children (10 after cardiac surgery, 4 with presumed septic shock, age: 0.75 to 166 months) were enrolled and received a loading dose followed by a continuous infusion of milrinone. Four to 9 timed blood samples were collected from each patient: prior to milrinone, at the end of the loading dose (Cl), -24 hours later (C2), prior to (C3), and after stopping the infusion. Milrinone concentration of extracted serum samples was measured by HPLC. The milrinone half-life (ti/z), steady state clearance (CLss), and volume of distribution (Vd) were calculated assuming Istorder elimination with an open 1-compartment model. Results: The loading dose of milrinone (48.5 ±1.9 meg/kg) resulted in Cl of 185 ± 60 ng/ml and continuous infusion (0.5 mcg/kg/min) was associated with C2 of 83.4 ± 29.1 ng/ml. At discontinuation of the drug (in 5.3 ±2.7 days) C3 was 61.4 ±18 ng/ml (C2 v C3, p-ns). CLss was 8.2 ±2.7 ml/kg/min, Vd was 0.66 ±0.38 Meg, and tm was 58 ±38 minutes. One patient developed multi-organ system failure (MOSF) and received an infusion of 0.25 mcg/kg/min: C3 was 241 ng/ml, milrinone concentration was >200 ng/ml 2 hours after stopping the infusion, CLss was 1.0 ml/kg/min and \\n was markedly prolonged (> 8 hours). Excluding the patient with MOSF, age was not correlated with any kinetic parameter. However, C2 increased with increasing serum creatinine and bilirubin (p<0.05) and Vd increased with increasing bilirubin (p<0.05). Conclusions: Milrinone pharmacokinetics in this group of critically ill children are similar to those in a small group of pédiatrie cardiac surgery patients [1]. A loading dose of 50 meg/kg followed by continuous infusion of 0.5 mcg/kg/min yielded drug concentrations initially in the range associated with effective therapy in adults (>100 ng/ml) [2]. However, the milrinone concentration declined to <100 ng/ A Huring the. infusion, suggesting the need to study increased infusion rates in children Milrinone clearance was substantially impaired in a child with MOSF. Until further kinetic data can be developed, milrinone should be used with great care, or avoided entirely, in children with MOSF.

Original languageEnglish (US)
JournalCritical Care Medicine
Volume26
Issue number1 SUPPL.
StatePublished - 1998
Externally publishedYes

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Milrinone
Critical Illness
Pharmacokinetics
Septic Shock
Serum
Bilirubin
Thoracic Surgery
Half-Life
Creatinine
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Scott Baird, J., Ushay, H. M., & Notterman, D. A. (1998). Milrinone pharmacokinetics in critically ill children. Critical Care Medicine, 26(1 SUPPL.).

Milrinone pharmacokinetics in critically ill children. / Scott Baird, J.; Ushay, Henry Michael; Notterman, Daniel A.

In: Critical Care Medicine, Vol. 26, No. 1 SUPPL., 1998.

Research output: Contribution to journalArticle

Scott Baird, J, Ushay, HM & Notterman, DA 1998, 'Milrinone pharmacokinetics in critically ill children', Critical Care Medicine, vol. 26, no. 1 SUPPL..
Scott Baird, J. ; Ushay, Henry Michael ; Notterman, Daniel A. / Milrinone pharmacokinetics in critically ill children. In: Critical Care Medicine. 1998 ; Vol. 26, No. 1 SUPPL.
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abstract = "Introduction: We investigated the pharmacokinetic characteristics of loading and continuous infusion therapy with railrinone in critically ill children, a group in which pharmacokinetic data are limited. Method: Fourteen children (10 after cardiac surgery, 4 with presumed septic shock, age: 0.75 to 166 months) were enrolled and received a loading dose followed by a continuous infusion of milrinone. Four to 9 timed blood samples were collected from each patient: prior to milrinone, at the end of the loading dose (Cl), -24 hours later (C2), prior to (C3), and after stopping the infusion. Milrinone concentration of extracted serum samples was measured by HPLC. The milrinone half-life (ti/z), steady state clearance (CLss), and volume of distribution (Vd) were calculated assuming Istorder elimination with an open 1-compartment model. Results: The loading dose of milrinone (48.5 ±1.9 meg/kg) resulted in Cl of 185 ± 60 ng/ml and continuous infusion (0.5 mcg/kg/min) was associated with C2 of 83.4 ± 29.1 ng/ml. At discontinuation of the drug (in 5.3 ±2.7 days) C3 was 61.4 ±18 ng/ml (C2 v C3, p-ns). CLss was 8.2 ±2.7 ml/kg/min, Vd was 0.66 ±0.38 Meg, and tm was 58 ±38 minutes. One patient developed multi-organ system failure (MOSF) and received an infusion of 0.25 mcg/kg/min: C3 was 241 ng/ml, milrinone concentration was >200 ng/ml 2 hours after stopping the infusion, CLss was 1.0 ml/kg/min and \\n was markedly prolonged (> 8 hours). Excluding the patient with MOSF, age was not correlated with any kinetic parameter. However, C2 increased with increasing serum creatinine and bilirubin (p<0.05) and Vd increased with increasing bilirubin (p<0.05). Conclusions: Milrinone pharmacokinetics in this group of critically ill children are similar to those in a small group of p{\'e}diatrie cardiac surgery patients [1]. A loading dose of 50 meg/kg followed by continuous infusion of 0.5 mcg/kg/min yielded drug concentrations initially in the range associated with effective therapy in adults (>100 ng/ml) [2]. However, the milrinone concentration declined to <100 ng/ A Huring the. infusion, suggesting the need to study increased infusion rates in children Milrinone clearance was substantially impaired in a child with MOSF. Until further kinetic data can be developed, milrinone should be used with great care, or avoided entirely, in children with MOSF.",
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N2 - Introduction: We investigated the pharmacokinetic characteristics of loading and continuous infusion therapy with railrinone in critically ill children, a group in which pharmacokinetic data are limited. Method: Fourteen children (10 after cardiac surgery, 4 with presumed septic shock, age: 0.75 to 166 months) were enrolled and received a loading dose followed by a continuous infusion of milrinone. Four to 9 timed blood samples were collected from each patient: prior to milrinone, at the end of the loading dose (Cl), -24 hours later (C2), prior to (C3), and after stopping the infusion. Milrinone concentration of extracted serum samples was measured by HPLC. The milrinone half-life (ti/z), steady state clearance (CLss), and volume of distribution (Vd) were calculated assuming Istorder elimination with an open 1-compartment model. Results: The loading dose of milrinone (48.5 ±1.9 meg/kg) resulted in Cl of 185 ± 60 ng/ml and continuous infusion (0.5 mcg/kg/min) was associated with C2 of 83.4 ± 29.1 ng/ml. At discontinuation of the drug (in 5.3 ±2.7 days) C3 was 61.4 ±18 ng/ml (C2 v C3, p-ns). CLss was 8.2 ±2.7 ml/kg/min, Vd was 0.66 ±0.38 Meg, and tm was 58 ±38 minutes. One patient developed multi-organ system failure (MOSF) and received an infusion of 0.25 mcg/kg/min: C3 was 241 ng/ml, milrinone concentration was >200 ng/ml 2 hours after stopping the infusion, CLss was 1.0 ml/kg/min and \\n was markedly prolonged (> 8 hours). Excluding the patient with MOSF, age was not correlated with any kinetic parameter. However, C2 increased with increasing serum creatinine and bilirubin (p<0.05) and Vd increased with increasing bilirubin (p<0.05). Conclusions: Milrinone pharmacokinetics in this group of critically ill children are similar to those in a small group of pédiatrie cardiac surgery patients [1]. A loading dose of 50 meg/kg followed by continuous infusion of 0.5 mcg/kg/min yielded drug concentrations initially in the range associated with effective therapy in adults (>100 ng/ml) [2]. However, the milrinone concentration declined to <100 ng/ A Huring the. infusion, suggesting the need to study increased infusion rates in children Milrinone clearance was substantially impaired in a child with MOSF. Until further kinetic data can be developed, milrinone should be used with great care, or avoided entirely, in children with MOSF.

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