106 A . Chevalier et al .: J Extra Corpor Technol 2024 , 56 , 101 – 107
experiments were conducted using a single , identical dose . As such , these experiments did not determine whether circuit adsorption can be saturated . However , ECMO oxygenators and CRRT filters have very large surface areas with a high availability of binding sites ; thus , saturation of circuit binding sites would be unlikely without exceedingly large doses of medications [ 16 ].
Our findings indicate that patients supported with ECLS likely require higher than standard doses of ketamine and dexmedetomidine to achieve therapeutic effects . While these data cannot be directly extrapolated to quantitative dose adjustments , the results of these experiments can be used to calculate pharmacokinetic parameters for ECMO and CRRT , allowing for the generation of ECLS compartments in physiologicallybased pharmacokinetic models . These models can then be used to generate dosing recommendations , which can in turn be validated through clinical pharmacokinetic studies [ 36 ].
Funding
Andrew Chevalier receives research support from the National Heart , Lung , and Blood Institute , ( T32HL105321 ). J . Porter Hunt receives support from the Utah Clinical Pharmacology Fellowship Program and a Thrasher Research Fund Early Career Award . Aviva Whelan receives support from The Indiana University-Ohio State University Maternal and Pediatric Precision in Therapeutics Data , Model , Knowledge , and Research Coordination Center ( IU-OSU MPRINT DMKRCC ), in part by Grant Number P30HD106451 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) Obstetrics and Pediatric Pharmacology and Therapeutics Branch ( OPPTB ). Autumn McKnite receives support from the National Institute of Diabetes and Digestive and Kidney Diseases ( F31DK130542 ). Kevin Watt receives research support from the National Institute of Child Health and Human Development ( R01HD097775 ).
Conflicts of interest The authors declare no conflict of interest .
Data availability statement All data are available upon request to the corresponding author .
Author contributions statement
KW designed the studies . AC , AM , AW , DG , and JPH performed the research . AC analyzed the data and wrote the manuscript . All authors contributed to the final version .
Ethics approval
The research did not involve human or animal subjects and was not subject to IRB review .
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