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Open Access Highly Accessed Study protocol

ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO

Kiran Shekar1*, Jason A Roberts2, Susan Welch3, Hergen Buscher3, Sam Rudham3, Fay Burrows3, Sussan Ghassabian4, Steven C Wallis2, Bianca Levkovich5, Vin Pellegrino5, Shay McGuinness6, Rachael Parke6, Eileen Gilder6, Adrian G Barnett7, James Walsham8, Daniel V Mullany1, Yoke L Fung1, Maree T Smith4 and John F Fraser1

Author Affiliations

1 Critical Care Research Group, Adult Intensive Care Services, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia

2 Burns Trauma and Critical Care Research Centre, Royal Brisbane and Women’s Hospital and The University of Queensland, Brisbane, Brisbane, Queensland, Australia

3 Intensive Care Services, St Vincent’s Hospital, Sydney, New South Wales, Australia

4 Centre for Integrated Preclinical Drug Development, University of Queensland, Brisbane, Queensland, Australia

5 Intensive Care Services, The Alfred Hospital, Melbourne, Victoria, Australia

6 Cardiothoracic & Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand

7 Institute of Health and Biomedical Innovation, School of Public Health & Social Work, Queensland University of Technology, Brisbane, Queensland, Australia

8 Intensive Care Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia

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BMC Anesthesiology 2012, 12:29  doi:10.1186/1471-2253-12-29

Published: 28 November 2012

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/Design

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.

Discussion

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.

Trial registration

ACTRN12612000559819

Keywords:
ECMO; Pharmacokinetics; Pharmacodynamics; Antibiotics; Sedatives; Analgesics; Therapeutic failure; Drug toxicity