Copyright © American Society of Artificial Internal Organs. Unauthorized reproduction of this article is prohibited. 1 ASAIO Journal 2018 Pediatric Circulatory Support From the *Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Bos- ton, Massachusetts; †Department of Anesthesiology, Maine Medical Center, Portland, Maine; ‡Pharmacometrics Research Core, Pharma- cokinetic Laboratory, Boston Children’s Hospital, Boston, Massachu- setts; §Department of Anesthesia and Pain Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada; and ¶Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts. Submitted for consideration December 2017; accepted for publica- tion 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, Perioperative and Pain Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. Email: viviane.nasr@child- rens.harvard.edu. 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 utiliz- ing 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 polymethylpen- tene 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 sam- ples 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 Phisio-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. ASAIO Journal XXX; XX:00–00. Key Words: extracorporeal membrane oxygenation, ECMO, sequestration, adsorption, sedation, ex vivo, dexmedetomi- dine, fentanyl, morphine Since its implementation in 1972, extracorporeal membrane oxygenation (ECMO) has been used in thousands of neonates and children with life-threatening cardiac or respiratory failure unresponsive to conventional therapies. 1 Children supported with ECMO require analgesia, sedation and in some instances neuromuscular blockade as part of routine care. Require- ments for sedation and analgesia vary among patients based on indication for ECMO, severity of illness, and risk of cannula dislodgement. Managing sedation and analgesia for patients on ECMO has become an important aspect of care both in the operating room and in the intensive care unit. Although multiple pharmacolog- ical therapies exist, achieving the desired level of sedation and analgesia while on ECMO remains a challenge. Extracorpo- real membrane oxygenation circuits have been shown to alter drug pharmacokinetics by increasing volume of distribution, decreasing systemic clearance and elimination, and through drug adsorption onto the ECMO circuit itself. 2–6 Sequestration of drugs in the tubing and membrane com- ponents of the ECMO circuit can result in lower drug concen- trations reaching the patient despite adjustment of drug doses to account for the larger volume of distribution associated with the ECMO circuit. Prior investigations utilizing ECMO circuits incorporating traditional silicone membrane oxygen- ators (MO), and nonheparin-coated polyvinylchloride (PVC) tubing have shown that lipophilic drugs such as midazolam and fentanyl are rapidly and thoroughly adsorbed by ECMO circuits with sequestration of as much as 100% of fentanyl at 24 hours after single bolus injection. 7,8 In current clinical prac- tice, PVC tubing is heparin coated and silicone MO have been replaced with polymethylpentene (PMP) MO to decrease size and increase efficiency. As such, previous studies character- izing the pharmacokinetic changes in ex vivo ECMO circuits may be less applicable to current clinical practice. In addition, in studies involving mixtures of medications, it is difficult to distinguish the relative contributions of drug–drug interaction from the net adsorption to the ECMO circuit vis-a-vis observed alterations in pharmacokinetics. 9,10 We sought to better characterize the individual adsorption of commonly used sedative and analgesic drugs fentanyl, mid- azolam, morphine, and dexmedetomidine in infant ECMO circuits utilizing a PMP membrane oxygenator and surface- coated PVC tubing. Materials and Methods This study was exempted from research approval by the institutional review board at Boston Children’s Hospital (BCH). Sedative and Analgesic Drug Sequestration After a Single Bolus Injection in an Ex Vivo Extracorporeal Membrane Oxygenation Infant Circuit VIVIANE G. NASR,* JONATHAN MESERVE,† LUIS M. PEREIRA,*‡ DAVID FARAONI,§ STEVE BREDIGER,¶ SUSAN GOOBIE,* RAVI THIAGARAJAN,¶ AND JAMES A. DINARDO* Copyright © 2018 by the ASAIO DOI: 10.1097/MAT.0000000000000793