title: ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO.
abstract: BACKGROUND
  Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO.
  
  
  METHODS
  This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO.
  
  
  CONCLUSIONS
  The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure.
  
  
  BACKGROUND
  ACTRN12612000559819.
authors.affiliation: Critical Care Research Group, Adult Intensive Care Services, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia. kiran_shekar@health.qld.gov.au.
authors.forename: Kiran
authors.initials: K
authors.lastname: Shekar
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Susan
authors.initials: S
authors.lastname: Welch
authors.forename: Hergen
authors.initials: H
authors.lastname: Buscher
authors.forename: Sam
authors.initials: S
authors.lastname: Rudham
authors.forename: Fay
authors.initials: F
authors.lastname: Burrows
authors.forename: Sussan
authors.initials: S
authors.lastname: Ghassabian
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.forename: Bianca
authors.initials: B
authors.lastname: Levkovich
authors.forename: Vin
authors.initials: V
authors.lastname: Pellegrino
authors.forename: Shay
authors.initials: S
authors.lastname: McGuinness
authors.forename: Rachael
authors.initials: R
authors.lastname: Parke
authors.forename: Eileen
authors.initials: E
authors.lastname: Gilder
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Barnett
authors.forename: James
authors.initials: J
authors.lastname: Walsham
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Mullany
authors.forename: Yoke L
authors.initials: YL
authors.lastname: Fung
authors.forename: Maree T
authors.initials: MT
authors.lastname: Smith
authors.forename: John F
authors.initials: JF
authors.lastname: Fraser