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Sedative and Analgesic Drug Sequestration After a Single Bolus Injection in an Ex Vivo Extracorporeal Membrane Oxygenation Infant Circuit

Nasr, Viviane G.*; Meserve, Jonathan; Pereira, Luis M.*,‡; Faraoni, David§; Brediger, Steve; Goobie, Susan*; Thiagarajan, Ravi; DiNardo, James A.*

doi: 10.1097/MAT.0000000000000793
Pediatric Circulatory Support

Patient sedation and analgesia on extracorporeal membrane oxygenation (ECMO) is vital for safety and comfort. However, adsorption to the circuit may alter drug pharmacokinetics and remains poorly characterized. This study characterizes drug adsorption of morphine, fentanyl, midazolam, and dexmedetomidine in an ex vivo infant ECMO circuit utilizing polymethylpentene (PMP) membrane oxygenator (MO) with protein-bounded polyvinylchloride (PVC) tubing. Twelve closed-loop ex vivo ECMO circuits were prepared using P.h.i.s.i.o (phosphorylcholine)-coated PVC tubing (Sorin Group USA, Inc.) and a Quadrox-iD pediatric polymethylpentene MO (Maquet Cardiopulmonary AG). Once the circuits were primed and running, a single medication was injected as a bolus into the circuit with three circuits per drug. Drug samples were drawn following injection, at 2, 5, 15, 30, 60, 120 minutes and at 4, 12, 24, 36, and 48 hours and analyzed using ultra high-performance liquid chromatography with mass spectrometry. Compared with morphine, the other drugs are highly sequestered with fentanyl 68.5%, dexmedetomidine 50.8%, and midazolam 26.2% affecting the availability of free drug in the circuit. Sequestration of fentanyl, midazolam, and dexmedetomidine in an ECMO circuit with P.h.i.s.i.o-coated PVC tubing and PMP MO may limit drug delivery to infants. Future in vivo studies are needed to determine the clinical impact of sequestration.

From the *Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts

Department of Anesthesiology, Maine Medical Center, Portland, Maine

Pharmacometrics Research Core, Pharmacokinetic Laboratory, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts

§Department of Anesthesia and Pain Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada

Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts.

Submitted for consideration December 2017; accepted for publication in revised form February 2018.

Disclosure: The authors have no conflicts of interest to report.

Supported by the Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA.

Correspondence: Viviane G. Nasr, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. Email: viviane.nasr@childrens.harvard.edu.

Copyright © 2019 by the American Society for Artificial Internal Organs