Presenter Status
Fellow
Abstract Type
Clinical Research
Primary Mentor or Principal Investigator
Kathryn Pavia, MD
Presentation Type
Poster
Start Date
19-5-2026 12:00 PM
End Date
19-5-2026 1:00 PM
Abstract Text
Background:
Dexmedetomidine is a highly hydrophilic alpha-2 agonist commonly used for sedation in critically ill patients to maintain devices and support. However, critical illness can prolong its elimination in the critically ill child. A problem that is likely due to reduced metabolic metabolism and increased volume of distribution.
Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO), further alters drug pharmacokinetics through increased distribution volume, reduced clearance, and drug sequestration with the circuit. Dexmedetomidine is known to adsorb to ECMO components; however, it currently comes from ex vivo studies circuit studies. Prospective data in vivo, particularly in pediatric populations and patients receiving multiple therapies (e.g., ECMO), remain sparse. Therefore, significant knowledge gaps persist regarding optimal dexmedetomidine dosing during ECMO treatment.
Objectives/Goal:
The primary goal of this study is to characterize the concentrations of dexmedetomidine in pediatric patients cannulated onto ECMO and describe major PK parameters in this population. The objective of this interim analysis is to describe the acceptability and feasibility of this sampling strategy in this population and to characterize the degree of interindividual variability among ECMO patients
This objective will test the hypothesis, dexmedetomidine concentrations will decrease immediately following ECMO cannulation and will then have a continued clearance
Methods/Design:
This is a prospective cohort study at a single tertiary care center which enrolls and stores samples under Critical and Acute Medication Pharmacology Repository (CAMPR) biorepository. Participants were eligible for inclusion if they were on a dexmedetomidine infusion at the time of cannulation onto ECMO. Parents or guardians provided consent. Samples were obtained using scavenged samples of blood. Dexmedetomidine concentrations were determined from plasma using a LC MS/MS assay with a lower limit of quantification of 0.1 ng/mL
Results:
Six patients were included in the primary analysis. Four patients (66%) are male, ages 1 day of life to 16 years, and all ICU’s are represented (3 NICU, 2 CICU, 1 PICU). All six patients were cannulated onto Veno/Arterial ECMO (5 peripheral and 1 central). Patients had a median of 1.5 (range 1-3) concentrations measured before cannulation and a median of 6.5 (range 6-10) concentrations measured in the 60 hours following cannulation. Dexmedetomidine infusion rates varied from 0.1 to 1.2 mcg/kg/hr.
Overall, 42/56 (75%) dexmedetomidine concentrations were quantifiable. Among quantifiable samples, the median dexmedetomidine concentration was 0.93 g/mL (range 0.112 - 4.88). Intra-individual variability was high with up to ~5 fold differences within samples obtained from the same patient receiving dexmedetomidine at the same infusion rate.
Conclusions:
This interim analysis demonstrates acceptability and feasibility of using scavenged sampling to study dexmedetomidine pharmacokinetics in the pediatric ECMO population. The variability thus far shows the importance of further analysis and more patient enrollment to identify the relative contributions of patient and circuit characteristics. And contrary to the hypothesis, the preliminary results do not support a consistent decline in dexmedetomidine around and following cannulation.
One prior study has evaluated plasma ECMO concentrations using 30 samples from 8 patients. Compared to the published literature, our cohort has greater variability in dexmedetomidine concentrations, potentially related to more diverse range of age and medical comorbidities in our study population.
Pharmacokinetic Profiles of Dexmedetomidine during Pediatric ECMO
Background:
Dexmedetomidine is a highly hydrophilic alpha-2 agonist commonly used for sedation in critically ill patients to maintain devices and support. However, critical illness can prolong its elimination in the critically ill child. A problem that is likely due to reduced metabolic metabolism and increased volume of distribution.
Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO), further alters drug pharmacokinetics through increased distribution volume, reduced clearance, and drug sequestration with the circuit. Dexmedetomidine is known to adsorb to ECMO components; however, it currently comes from ex vivo studies circuit studies. Prospective data in vivo, particularly in pediatric populations and patients receiving multiple therapies (e.g., ECMO), remain sparse. Therefore, significant knowledge gaps persist regarding optimal dexmedetomidine dosing during ECMO treatment.
Objectives/Goal:
The primary goal of this study is to characterize the concentrations of dexmedetomidine in pediatric patients cannulated onto ECMO and describe major PK parameters in this population. The objective of this interim analysis is to describe the acceptability and feasibility of this sampling strategy in this population and to characterize the degree of interindividual variability among ECMO patients
This objective will test the hypothesis, dexmedetomidine concentrations will decrease immediately following ECMO cannulation and will then have a continued clearance
Methods/Design:
This is a prospective cohort study at a single tertiary care center which enrolls and stores samples under Critical and Acute Medication Pharmacology Repository (CAMPR) biorepository. Participants were eligible for inclusion if they were on a dexmedetomidine infusion at the time of cannulation onto ECMO. Parents or guardians provided consent. Samples were obtained using scavenged samples of blood. Dexmedetomidine concentrations were determined from plasma using a LC MS/MS assay with a lower limit of quantification of 0.1 ng/mL
Results:
Six patients were included in the primary analysis. Four patients (66%) are male, ages 1 day of life to 16 years, and all ICU’s are represented (3 NICU, 2 CICU, 1 PICU). All six patients were cannulated onto Veno/Arterial ECMO (5 peripheral and 1 central). Patients had a median of 1.5 (range 1-3) concentrations measured before cannulation and a median of 6.5 (range 6-10) concentrations measured in the 60 hours following cannulation. Dexmedetomidine infusion rates varied from 0.1 to 1.2 mcg/kg/hr.
Overall, 42/56 (75%) dexmedetomidine concentrations were quantifiable. Among quantifiable samples, the median dexmedetomidine concentration was 0.93 g/mL (range 0.112 - 4.88). Intra-individual variability was high with up to ~5 fold differences within samples obtained from the same patient receiving dexmedetomidine at the same infusion rate.
Conclusions:
This interim analysis demonstrates acceptability and feasibility of using scavenged sampling to study dexmedetomidine pharmacokinetics in the pediatric ECMO population. The variability thus far shows the importance of further analysis and more patient enrollment to identify the relative contributions of patient and circuit characteristics. And contrary to the hypothesis, the preliminary results do not support a consistent decline in dexmedetomidine around and following cannulation.
One prior study has evaluated plasma ECMO concentrations using 30 samples from 8 patients. Compared to the published literature, our cohort has greater variability in dexmedetomidine concentrations, potentially related to more diverse range of age and medical comorbidities in our study population.
Comments
Poster Board Number: 20