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The relationship between simulated milrinone exposure and hypotension in children.

Publication ,  Journal Article
Commander, SJ; Gonzalez, D; Kumar, KR; Spears, T; Cohen-Wolkowiez, M; Zimmerman, KO; Balevic, SJ; Hornik, CP
Published in: Cardiol Young
May 2022

INTRODUCTION: Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure-safety relationship is unknown. METHODS: Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines. Clinically significant hypotension was defined as hypotension with concomitant lactate >3 mg/dl. A prior population pharmacokinetic model was used to simulate milrinone exposures to evaluate exposure-safety relationships. RESULTS: We included 399 children with a median (quarter 1, quarter 3) age of 1 year (0,5) who received 428 intravenous doses of milrinone (median infusion rate 0.31 mcg/kg/min [0.29,0.5]). Median maximum plasma milrinone concentration was 110.7 ng/ml (48.4,206.2). Median lowest systolic and diastolic blood pressures were 74 mmHg (60,85) and 35 mmHg (25,42), respectively. At least 1 episode of hypotension occurred in 178 (45%) subjects; clinically significant hypotension occurred in 10 (2%). The maximum simulated milrinone plasma concentrations were higher in subjects with clinically significant hypotension (251 ng/ml [129,329]) versus with hypotension alone (86 ng/ml [44, 173]) versus without hypotension (122 ng/ml [57, 208], p = 0.002); however, this relationship was not retained on multivariable analysis (odds ratio 1.01; 95% confidence interval 0.998, 1.01). CONCLUSIONS: We successfully leveraged a population pharmacokinetic model and electronic health record data to evaluate the relationship between simulated plasma concentration of milrinone and systemic hypotension occurrence, respectively, supporting the broader applicability of our novel, efficient, and cost-effective study design for examining drug exposure-response and -safety relationships.

Duke Scholars

Published In

Cardiol Young

DOI

EISSN

1467-1107

Publication Date

May 2022

Volume

32

Issue

5

Start / End Page

782 / 788

Location

England

Related Subject Headings

  • Milrinone
  • Hypotension
  • Humans
  • Hemodynamics
  • Child
  • Cardiovascular System & Hematology
  • Cardiotonic Agents
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Commander, S. J., Gonzalez, D., Kumar, K. R., Spears, T., Cohen-Wolkowiez, M., Zimmerman, K. O., … Hornik, C. P. (2022). The relationship between simulated milrinone exposure and hypotension in children. Cardiol Young, 32(5), 782–788. https://doi.org/10.1017/S1047951121003103
Commander, Sarah Jane, Daniel Gonzalez, Karan R. Kumar, Tracy Spears, Michael Cohen-Wolkowiez, Kanecia O. Zimmerman, Stephen J. Balevic, and Christoph P. Hornik. “The relationship between simulated milrinone exposure and hypotension in children.Cardiol Young 32, no. 5 (May 2022): 782–88. https://doi.org/10.1017/S1047951121003103.
Commander SJ, Gonzalez D, Kumar KR, Spears T, Cohen-Wolkowiez M, Zimmerman KO, et al. The relationship between simulated milrinone exposure and hypotension in children. Cardiol Young. 2022 May;32(5):782–8.
Commander, Sarah Jane, et al. “The relationship between simulated milrinone exposure and hypotension in children.Cardiol Young, vol. 32, no. 5, May 2022, pp. 782–88. Pubmed, doi:10.1017/S1047951121003103.
Commander SJ, Gonzalez D, Kumar KR, Spears T, Cohen-Wolkowiez M, Zimmerman KO, Balevic SJ, Hornik CP. The relationship between simulated milrinone exposure and hypotension in children. Cardiol Young. 2022 May;32(5):782–788.
Journal cover image

Published In

Cardiol Young

DOI

EISSN

1467-1107

Publication Date

May 2022

Volume

32

Issue

5

Start / End Page

782 / 788

Location

England

Related Subject Headings

  • Milrinone
  • Hypotension
  • Humans
  • Hemodynamics
  • Child
  • Cardiovascular System & Hematology
  • Cardiotonic Agents
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology