Ketamine Extraction by Extracorporeal Life Support Circuits

Monday, January 22, 2024

9:40 AM – 9:50 AM MT

Location: Connections Central - Star Research Theater

Star Research Presenters(s)

AC

Andrew Chevalier

University of Utah
Salt Lake City, UT

Co-Author(s)

Danielle J. Green, MD

PICU Attending
Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, USA; Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, USA
Salt Lake City, UT, United States
RH

Rachel Hudson, PhD

Postdoc
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA, United States
JH

J. Porter Hunt, PhD

Postdoc
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, USA, United States
AM

Autumn McKnite, BS

Phd Candidate
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA, United States
AW

Aviva Whelan, MD

PICU Fellow
Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, USA, United States
KW

Kevin Watt, MD, PhD

PICU Attending
Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, USA; Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, USA, United States

Introduction: Patients supported with extracorporeal life support (ECLS) circuits such as ECMO and CRRT often require high doses of sedatives and analgesics for patient tolerance, leading to the increased use of ketamine for its opioid and benzodiazepine sparing effects. Ketamine concentrations are likely affected by ECLS circuits through adsorption to the circuit components, clearance by the CRRT filter, as well as the large volume of blood used to prime the circuits. However, the impact of ECLS circuits on ketamine pharmacokinetics has not been well described. This study will determine ketamine extraction by extracorporeal circuits in an ex vivo model.

Methods: Ketamine was administered at physiologic concentration to blood-primed, closed-loop ex vivo ECMO and CRRT circuits. ECMO experiments (n=3) were performed with a Maquet Bioline centrifugal pump, Medtronix custom perfusion tubing, and a Maquet adult Quadrox iD Bioline oxygenator. CRRT experiments (n=3) were performed with the Baxter Prismax dialysis machine, using HF-1000 filters in a continuous hemodiafiltration (CVVHDF) configuration. Drug concentrations were measured in plasma, hemofiltrate, and control samples at multiple time points over the course of the experiments (8h ECMO, 5h CRRT). At each sample time point, percent of drug recovery and CRRT saturation coefficient was calculated. Two-sample t-tests were used to compare the recovery at the end of the experiment between the ECLS circuits and the control samples.

Results: Ketamine plasma concentration in the ECMO circuits decreased rapidly, with 43.8% recovery (SD=0.5%) after 8 hours. Clearance by the CRRT circuit was more complete, with around 5% recovery (SD=1%) after 5 hours. In contrast, ketamine concentrations were very stable in the control samples, with approximately 100% drug recovery after 8 hours. At the end of the experiment, ketamine plasma concentrations differed significantly between ECLS circuits and the control samples for both ECMO (p < 0.0001) and CRRT (p < 0.0001). Average saturation coefficient was 68% (SD=10%).

Conclusions: Ketamine concentrations are significantly affected by both ECMO and CRRT circuits. These data can be incorporated into a pharmacokinetic model to optimize dosing in patients supported with ECLS.