A Population Pharmacokinetic Model of Intravenous Dexmedetomidine for Mechanically Ventilated Children after Neurosurgery

Autor: Jin-Tae Kim, Hee-Soo Kim, Sojeong Yi, Hyeong-Seok Lim, Joo Youn Cho, Eun Hee Kim, Ji Hyun Lee, In-Kyung Song, Min-Chang Kim
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Medicine
Volume 8
Issue 10
Journal of Clinical Medicine, Vol 8, Iss 10, p 1563 (2019)
ISSN: 2077-0383
DOI: 10.3390/jcm8101563
Popis: Dexmedetomidine is a selective alpha-2 adrenergic agonist with concurrent sedative and analgesic effects, and it is being increasingly used in pediatric anesthesia and intensive care. This study aimed to investigate the pharmacokinetics of intravenous dexmedetomidine in mechanically ventilated children in the intensive care unit (ICU) after neurosurgery. Pediatric patients aged 2&ndash
12 years, who were mechanically ventilated in ICU after neurosurgery, were allocated into a low-dose (n = 15) or high-dose (n = 14) group. The low-dose group received dexmedetomidine at a loading dose of 0.25 µ
g/kg for 10 min, followed by a maintenance dose of 0.25 µ
g/kg/h for 50 min, whereas the high-dose group received dexmedetomidine at a loading dose of 0.5 µ
g/kg for 10 min, followed by a maintenance dose of 0.5 µ
g/kg/h for 50 min. Serial blood samples were collected for a pharmacokinetic analysis up to 480 min after the end of the infusion. The sedative effect of dexmedetomidine was assessed using the Bispectral Index and University of Michigan Sedation Scale. Adverse reactions, electrocardiography findings, and vital signs were monitored for a safety assessment. A population pharmacokinetic analysis was performed using non-linear mixed effects modeling. Dexmedetomidine induced a moderate-to-deep degree of sedation during infusion in both groups. The pharmacokinetics of dexmedetomidine were best described by a two-compartment disposition model with first-order elimination kinetics. The parameters were standardized for a body weight of 70 kg using an allometric power model. The population estimates (95% confidence interval) per 70 kg body weight were as follows: clearance of 81.0 (72.9&ndash
90.9) L/h, central volume of distribution of 64.2 (50.6&ndash
81.0) L, intercompartment clearance of 116.4 (90.6&ndash
156.0) L/h, and peripheral volume of distribution of 167 (132&ndash
217) L. No serious adverse reactions or hemodynamic changes requiring the discontinuation of dexmedetomidine were observed. Dexmedetomidine had increased clearance and volume of distribution in mechanically ventilated children in ICU after neurosurgery, thereby indicating the need to adjust the dosage to obtain a target plasma concentration.
Databáze: OpenAIRE
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