Dexmedetomidine in Children on Extracorporeal Membrane Oxygenation: Pharmacokinetic Data Exploration Using Previously Published Models

被引:4
作者
Thibault, Celine [1 ]
Zuppa, Athena F. [1 ]
机构
[1] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA
关键词
extracorporeal membrane oxygenation; neonates; sedation; dexmedetomidine; pediatrics; pharmacokinetics; pharmacology; analgesia; AUGMENTED RENAL CLEARANCE; PEDIATRIC INTENSIVE-CARE; POPULATION PHARMACOKINETICS; PREDICTIVE PERFORMANCE; PROLONGED SEDATION; INFUSION; INFANTS; SAFETY; PICU;
D O I
10.3389/fped.2022.924829
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
BackgroundDexmedetomidine is a sedative and analgesic increasingly used in children supported with extracorporeal membrane oxygenation (ECMO). No data is available to describe the pharmacokinetics (PK) of dexmedetomidine in this population. MethodsWe performed a single-center prospective PK study. Children <18 years old, supported with ECMO, and on a dexmedetomidine infusion as part of their management were prospectively included. PK samples were collected. Dexmedetomidine dosing remained at the discretion of the clinical team. Six population PK models built in pediatrics were selected. Observed concentrations were compared with population predicted concentrations using the PK models. ResultsEight children contributed 30 PK samples. None of the PK models evaluated predicted the concentrations with acceptable precision and bias. Four of the six evaluated models overpredicted the concentrations. The addition of a correction factor on clearance improved models' fit. Two of the evaluated models were not applicable to our whole population age range because of their structure. ConclusionMost of the evaluated PK models overpredicted the concentrations, potentially indicating increased clearance on ECMO. Population PK models applicable to a broad spectrum of ages and pathologies are more practical in pediatric critical care settings but challenging to develop.
引用
收藏
页数:7
相关论文
共 36 条
[1]   Population Pharmacokinetics of Midazolam and Its Metabolites during Venoarterial Extracorporeal Membrane Oxygenation in Neonates [J].
Ahsman, Maurice J. ;
Hanekamp, Manon ;
Wildschut, Enno D. ;
Tibboel, Dick ;
Mathot, Ron A. A. .
CLINICAL PHARMACOKINETICS, 2010, 49 (06) :407-419
[2]   Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube [J].
Ahsman, Maurice J. ;
Witjes, Bregje C. ;
Wildschut, Enno D. ;
Sluiter, Ilona ;
Vulto, Arnold G. ;
Tibboel, Dick ;
Mathot, Ron A. .
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, 2010, 95 (02) :F109-F114
[3]   Pharmacokinetics and Safety of Micafungin in Infants Supported With Extracorporeal Membrane Oxygenation [J].
Autmizguine, Julie ;
Hornik, Christoph P. ;
Benjamin, Daniel K., Jr. ;
Brouwer, Kim L. R. ;
Hupp, Susan R. ;
Cohen-Wolkowiez, Michael ;
Watt, Kevin M. .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2016, 35 (11) :1204-1210
[4]   Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically III Pediatric Patients [J].
Avedissian, Sean N. ;
Bradley, Erin ;
Zhang, Diana ;
Bradley, John S. ;
Nazer, Lama H. ;
Tran, Tri M. ;
Nguyen, Austin ;
Le, Jennifer .
PEDIATRIC CRITICAL CARE MEDICINE, 2017, 18 (09) :E388-E394
[5]   Dexmedetomidine Use in a Pediatric Intensive Care Unit: A Retrospective Cohort Study [J].
Banasch, Heidi L. ;
Dersch-Mills, Deonne A. ;
Boulter, Leah L. ;
Gilfoyle, Elaine .
ANNALS OF PHARMACOTHERAPY, 2018, 52 (02) :133-139
[6]   The effect of pathophysiology on pharmacokinetics in the critically ill patient - Concepts appraised by the example of antimicrobial agents [J].
Blot, Stijn I. ;
Pea, Federico ;
Lipman, Jeffrey .
ADVANCED DRUG DELIVERY REVIEWS, 2014, 77 :3-11
[7]   Cytochrome P450 mediated-drug metabolism is reduced in children with sepsis-induced multiple organ failure [J].
Carcillo, JA ;
Doughty, L ;
Kofos, D ;
Frye, RF ;
Kaplan, SS ;
Sasser, H ;
Burckart, GJ .
INTENSIVE CARE MEDICINE, 2003, 29 (06) :980-984
[8]   Dexmedetomidine extraction by the extracorporeal membrane oxygenation circuit: results from an in vitro study [J].
Dallefeld, Samantha H. ;
Sherwin, Jennifer ;
Zimmerman, Kanecia O. ;
Watt, Kevin M. .
PERFUSION-UK, 2020, 35 (03) :209-216
[9]   Pharmacokinetics of Dexmedetomidine in Infants and Children After Orthotopic Liver Transplantation [J].
Damian, Mihaela A. ;
Hammer, Gregory B. ;
Elkomy, Mohammed H. ;
Frymoyer, Adam ;
Drover, David R. ;
Su, Felice .
ANESTHESIA AND ANALGESIA, 2020, 130 (01) :209-216
[10]   Dexmedetomidine for Prolonged Sedation in the PICU: A Systematic Review and Meta-Analysis* [J].
Daverio, Marco ;
Sperotto, Francesca ;
Zanetto, Lorenzo ;
Coscini, Nadia ;
Frigo, Anna Chiara ;
Mondardini, Maria Cristina ;
Amigoni, Angela .
PEDIATRIC CRITICAL CARE MEDICINE, 2020, 21 (07) :E467-E474