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A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients

STUDY OBJECTIVE: Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response c...

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Autores principales: Gallaway, Katherine A., Skaar, Todd C., Biju, Ashwin, Slaven, James, Tillman, Emma M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325491/
https://www.ncbi.nlm.nih.gov/pubmed/35429176
http://dx.doi.org/10.1002/phar.2684
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author Gallaway, Katherine A.
Skaar, Todd C.
Biju, Ashwin
Slaven, James
Tillman, Emma M.
author_facet Gallaway, Katherine A.
Skaar, Todd C.
Biju, Ashwin
Slaven, James
Tillman, Emma M.
author_sort Gallaway, Katherine A.
collection PubMed
description STUDY OBJECTIVE: Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children. DESIGN: We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children. MEASUREMENTS AND MAIN RESULTS: Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom‐designed TaqMan® Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3–1.2), GC (1, 0.3–1.3), and GG (0.8, 0.3–1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24–1.07), 0.72 (0.22–0.98), 0.58 (0.3–0.94), (p = 0.67). CONCLUSIONS: These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics.
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spelling pubmed-93254912022-07-30 A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients Gallaway, Katherine A. Skaar, Todd C. Biju, Ashwin Slaven, James Tillman, Emma M. Pharmacotherapy Original Research Articles STUDY OBJECTIVE: Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children. DESIGN: We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children. MEASUREMENTS AND MAIN RESULTS: Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom‐designed TaqMan® Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3–1.2), GC (1, 0.3–1.3), and GG (0.8, 0.3–1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24–1.07), 0.72 (0.22–0.98), 0.58 (0.3–0.94), (p = 0.67). CONCLUSIONS: These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics. John Wiley and Sons Inc. 2022-04-20 2022-06 /pmc/articles/PMC9325491/ /pubmed/35429176 http://dx.doi.org/10.1002/phar.2684 Text en © 2022 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research Articles
Gallaway, Katherine A.
Skaar, Todd C.
Biju, Ashwin
Slaven, James
Tillman, Emma M.
A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients
title A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients
title_full A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients
title_fullStr A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients
title_full_unstemmed A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients
title_short A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients
title_sort pilot study of adra2a genotype association with doses of dexmedetomidine for sedation in pediatric patients
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325491/
https://www.ncbi.nlm.nih.gov/pubmed/35429176
http://dx.doi.org/10.1002/phar.2684
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