J Extra Corpor Technol 2023 , 55 , 194 – 196 Ó The Author ( s ), published by EDP Sciences , 2023 https :// doi . org / 10.1051 / ject / 2023036
Available online at : ject . edpsciences . org
TECHNIQUE OR APPLICATION
Direct and continuous dosing of propofol can saturate Ex vivo ECMO circuit to improve propofol recovery
Nitish Khurana ( PhD ) 1 , Till Sünner 2 , Oliver Hubbard 3 , Carina E . Imburgia 4 , Venkata Yellepeddi ( PhD ) 1 , 4 , Hamidreza Ghandehari ( PhD ) 1 , 3 , and Kevin M . Watt ( PhD ) 4 ,*
1 Utah Center for Nanomedicine , Department of Molecular Pharmaceutics , College of Pharmacy , University of Utah , Salt Lake City , Utah 84112 , USA 2 Philipps Universität Marburg , Institut für Pharmazeutische Technologie und Biopharmazie , Robert-Koch-Straße 4 , 35037 Marburg ,
Germany 3 Department of Biomedical Engineering , College of Engineering , University of Utah , 36 S . Wasatch , Salt Lake City , Utah 84112 , USA 4 Division of Clinical Pharmacology , Department of Pediatrics , School of Medicine , University of Utah , 295 Chipeta Way ,
Salt Lake City , Utah 84108 , USA Received 30 March 2023 , Accepted 28 July 2023
Abstract – Background : Extracorporeal membrane oxygenation ( ECMO ) is a cardiopulmonary bypass device that provides life-saving complete respiratory and cardiac support in patients with cardiorespiratory failure . The majority of drugs prescribed to patients on ECMO lack a dosing strategy optimized for ECMO patients . Several studies demonstrated that dosing is different in this population because the ECMO circuit components can adsorb drugs and affect drug exposure substantially . Saturation of ECMO circuit components by drug disposition has been posited but has not been proven . In this study , we have attempted to determine if propofol adsorption is saturable in ex vivo ECMO circuits . Methods : We injected ex vivo ECMO circuits with propofol , a drug that is highly adsorbed to the ECMO circuit components . Propofol was injected as a bolus dose ( 50 lg / mL ) and a continuous infusion dose ( 6 mg / h ) to investigate the saturation of the ECMO circuit . Results : After the bolus dose , only 27 % of propofol was recovered after 30 minutes which is as expected . However , > 80 % propofol was recovered after the infusion dose which persisted even when the infusion dose was discontinued . Conclusion : Our results suggest that if ECMO circuits are dosed directly with propofol , drug adsorption can be eliminated as a cause for altered drug exposure .
Field of Research : Artificial Lung / ECMO Key words : ECMO , Propofol , Saturation , Dosing .
Overview
Extracorporeal membrane oxygenator ( ECMO ) is a cardiopulmonary bypass device that provides complete respiratory and cardiac support in patients with severe cardiopulmonary failure and is a lifesaving technology for critically ill patients . Critically ill patients on ECMO are prescribed multiple drugs but the dosing for most drugs is unknown . Dosing for this population is different due to 1 ) direct adsorption of drugs by the circuit , 2 ) clearance by the circuits ( e . g ., hemofiltration ), and 3 ) critical illness physiology which affects drug absorption , distribution , metabolism , and elimination [ 1 , 2 ]. Altered drug pharma- cokinetics ( PK ) can result in suboptimal dosing and place patients at risk for subtherapeutic exposure and toxicity [ 3 ].
Adsorption of the drug to circuit components is primarily driven by hydrophobic and electrostatic interactions [ 4 ]. Studies
* Corresponding author : kevin . watt @ hsc . utah . edu have suggested that this process might be saturable but this has never been proven [ 5 , 6 ]. Propofol is a commonly used sedative that is highly lipophilic ( logP = 3.8 ) and protein-bound ( 98 %) and is known to be adsorbed by the ECMO circuit . Prior studies have demonstrated that up to 70 % of propofol was adsorbed within 30 minutes of administering a bolus dose to the ex vivo ECMO circuit [ 7 – 9 ]. In this study , we repeated the single dose experiment and additionally gave a 2-hour infusion of propofol to determine if propofol adsorption was saturable in a pediatric ex vivo ECMO circuit .
Description
ECMO circuits were assembled according to standard practice with a Quadrox iD oxygenator with bioline coating , Rotaflow R32 pump with bioline coating and custom perfusion tubing . Circuits were set up in a closed loop with an IV bag
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