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Perioperative Acetaminophen Dosing in Obese Children

Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1–10). Postoperative maintenance dosing is used to keep...

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Autores principales: Anderson, Brian Joseph, Cortinez, Luis Ignacio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136941/
https://www.ncbi.nlm.nih.gov/pubmed/37189874
http://dx.doi.org/10.3390/children10040625
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author Anderson, Brian Joseph
Cortinez, Luis Ignacio
author_facet Anderson, Brian Joseph
Cortinez, Luis Ignacio
author_sort Anderson, Brian Joseph
collection PubMed
description Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1–10). Postoperative maintenance dosing is used to keep this effect at a steady-state concentration. The loading dose in children is commonly prescribed per kilogram. That dose is consistent with the linear relationship between the volume of distribution and total body weight. Total body weight is made up of both fat and fat-free mass. The fat mass has little influence on the volume of distribution of acetaminophen but fat mass should be considered for maintenance dosing that is determined by clearance. The relationship between the pharmacokinetic parameter, clearance, and size is not linear. A number of size metrics (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale clearance and all consequent dosing schedules recognize curvilinear relationships between clearance and size. This relationship can be described using allometric theory. Fat mass also has an indirect influence on clearance that is independent of its effects due to increased body mass. Normal fat mass, used in conjunction with allometry, has proven a useful size metric for acetaminophen; it is calculated using fat-free mass and a fraction (Ffat) of the additional mass contributing to total body weight. However, the Ffat for acetaminophen is large (Ffat = 0.82), pharmacokinetic and pharmacodynamic parameter variability high, and the concentration–response slope gentle at the target concentration. Consequently, total body weight with allometry is acceptable for the calculation of maintenance dose. The dose of acetaminophen is tempered by concerns about adverse effects, notably hepatotoxicity associated with use after 2–3 days at doses greater than 90 mg/kg/day.
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spelling pubmed-101369412023-04-28 Perioperative Acetaminophen Dosing in Obese Children Anderson, Brian Joseph Cortinez, Luis Ignacio Children (Basel) Review Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1–10). Postoperative maintenance dosing is used to keep this effect at a steady-state concentration. The loading dose in children is commonly prescribed per kilogram. That dose is consistent with the linear relationship between the volume of distribution and total body weight. Total body weight is made up of both fat and fat-free mass. The fat mass has little influence on the volume of distribution of acetaminophen but fat mass should be considered for maintenance dosing that is determined by clearance. The relationship between the pharmacokinetic parameter, clearance, and size is not linear. A number of size metrics (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale clearance and all consequent dosing schedules recognize curvilinear relationships between clearance and size. This relationship can be described using allometric theory. Fat mass also has an indirect influence on clearance that is independent of its effects due to increased body mass. Normal fat mass, used in conjunction with allometry, has proven a useful size metric for acetaminophen; it is calculated using fat-free mass and a fraction (Ffat) of the additional mass contributing to total body weight. However, the Ffat for acetaminophen is large (Ffat = 0.82), pharmacokinetic and pharmacodynamic parameter variability high, and the concentration–response slope gentle at the target concentration. Consequently, total body weight with allometry is acceptable for the calculation of maintenance dose. The dose of acetaminophen is tempered by concerns about adverse effects, notably hepatotoxicity associated with use after 2–3 days at doses greater than 90 mg/kg/day. MDPI 2023-03-27 /pmc/articles/PMC10136941/ /pubmed/37189874 http://dx.doi.org/10.3390/children10040625 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Anderson, Brian Joseph
Cortinez, Luis Ignacio
Perioperative Acetaminophen Dosing in Obese Children
title Perioperative Acetaminophen Dosing in Obese Children
title_full Perioperative Acetaminophen Dosing in Obese Children
title_fullStr Perioperative Acetaminophen Dosing in Obese Children
title_full_unstemmed Perioperative Acetaminophen Dosing in Obese Children
title_short Perioperative Acetaminophen Dosing in Obese Children
title_sort perioperative acetaminophen dosing in obese children
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136941/
https://www.ncbi.nlm.nih.gov/pubmed/37189874
http://dx.doi.org/10.3390/children10040625
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