J Extra Corpor Technol 2024 , 56 , 101 – 107 Ó The Author ( s ), published by EDP Sciences , 2024 https :// doi . org / 10.1051 / ject / 2024016
Available online at : ject . edpsciences . org
ORIGINAL ARTICLE
Extraction of ketamine and dexmedetomidine by extracorporeal life support circuits w
Andrew Chevalier ( MD ) 1 , J . Porter Hunt ( PhD ) 2 , Aviva Whelan ( MD ) 1 , Autumn McKnite ( PhD ) 3 , Kevin M . Watt ( MD , PhD ) 1 , 2 ,* , and Danielle J . Green ( MD ) 1 , 2
1 Division of Pediatric Critical Care , Department of Pediatrics , University of Utah , Salt Lake City , UT 84132 , USA 2 Division of Clinical Pharmacology , Department of Pediatrics , University of Utah , Salt Lake City , UT 84132 , USA 3 Department of Pharmacology and Toxicology , University of Utah , Salt Lake City , UT 84132 , USA
Received 11 March 2024 , Accepted 12 June 2024
Abstract – Background : Patients supported with extracorporeal life support ( ECLS ) circuits such as ECMO and CRRT often require high doses of sedatives and analgesics , including ketamine and dexmedetomidine . Concentrations of many medications are affected by ECLS circuits through adsorption to the circuit components , dialysis , as well as the large volume of blood used to prime the circuits . However , the impact of ECLS circuits on ketamine and dexmedetomidine pharmacokinetics has not been well described . This study determined ketamine and dexmedetomidine extraction by extracorporeal circuits in an ex-vivo system . Methods : Medication was administered at therapeutic concentration to blood-primed , closed-loop ex-vivo ECMO and CRRT circuits . Drug concentrations were measured in plasma , hemofiltrate , and control samples at multiple time points throughout the experiments . At each sample time point , the percentage of drug recovery was calculated . Results : Ketamine plasma concentration in the ECMO and CRRT circuits decreased rapidly , with 43.8 % recovery ( SD = 0.6 %) from ECMO circuits after 8 h and 3.3 % ( SD = 1.8 %) recovery from CRRT circuits after 6 h . Dexmedetomidine was also cleared from CRRT circuits , with 20.3 % recovery ( SD = 1.8 %) after 6 h . Concentrations of both medications were very stable in the control experiments , with approximately 100 % drug recovery of both ketamine and dexmedetomidine after 6 h . Conclusion : Ketamine and dexmedetomidine concentrations are significantly affected by ECLS circuits , indicating that dosing adjustments are needed for patients supported with ECMO and CRRT .
Key words : ECMO , Pharmacology , Dialysis , Sedation , ECLS .
Introduction
Extracorporeal life support ( ECLS ) circuits , including extracorporeal membrane oxygenation ( ECMO ) and continuous renal replacement therapy ( CRRT ), are potentially life-saving therapies for patients with refractory organ failure [ 1 – 3 ]. Almost universally , patients who are supported with ECLS require sedation to maintain patient safety and comfort [ 4 ] Drug exposure resulting from standard dosing of these medications may be significantly affected by ECLS circuits . ECLS circuits alter medication concentrations in the following ways : 1 ) adsorption of medication to circuit components ; 2 ) clearance of medication via dialysis ; and 3 ) increased volume of distribution from a circuit prime [ 5 ]. Medications that are highly protein-bound and lipophilic tend to be most affected by adsorption ; hydrophilic , minimally protein-bound medications tend to be cleared by dialysis [ 5 , 6 ]. As sedatives tend to be lipophilic , a high degree of interaction with ECLS circuits is expected . Understanding these interactions is critical to avoiding treatment failure .
Ketamine and dexmedetomidine are two sedating medications that are recommended by national guidelines for use in critically ill patients [ 7 , 8 ]. Ketamine , an NMDA receptor antagonist , is a medication that has sedating , amnestic , and analgesic effects . In contrast to most sedatives , ketamine does not tend to lower blood pressure , making it especially useful for patients at risk of hemodynamic instability , such as those on ECLS . Additionally , ketamine confers the added benefit of bronchodilation , thus leading to its use in refractory status asthmaticus . Finally , ketamine has been demonstrated to have an opioid and benzodiazepine-sparing effect [ 9 ]. Unfortunately , if used in excess , ketamine may contribute to hypertension , tachycardia , excess pulmonary secretions , or worsened delirium . Dexmedetomidine , an agonist at central alpha-2 receptors ,
w Meeting : Critical Care Congress , Society of Critical Care Medicine , Phoenix , AZ , USA , 1 / 21-1 / 23 / 24 * Corresponding author : kevin . watt @ hsc . utah . edu
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