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Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation

Kiran Shekar1*, Jason A Roberts2, Charles I Mcdonald1, Stephanie Fisquet1, Adrian G Barnett3, Daniel V Mullany1, Sussan Ghassabian4, Steven C Wallis2, 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 & The University of Queensland, Rode Road, Chermiside, Queensland, Australia, 4032

2 Burns Trauma and Critical Care Research Centre, The University of Queensland, Cnr Butterfield St and Bowen Bridge Rd, Herston, Queensland, Australia, 4029

3 Institute of Health and Biomedical Innovation, School of Public Health & Social Work, Queensland University of Technology, Cnr Musk and Victoria Park Rd, Kelvin Grove, Queensland, Australia, 4059

4 Centre for Integrated Preclinical Drug Development, Cnr Butterfield St and Bowen Bridge Rd Herston, The University of Queensland, Queensland, Australia, 4029

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Critical Care 2012, 16:R194  doi:10.1186/cc11679

Published: 15 October 2012

Abstract

Introduction

Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits.

Methods

Four identical ECMO circuits were set up as per the standard protocol for adult patients on ECMO. The circuits were primed with crystalloid and albumin, followed by fresh human whole blood, and were maintained at a physiological pH and temperature for 24 hours. After baseline sampling, fentanyl, morphine, midazolam, meropenem and vancomycin were injected into the circuit at therapeutic concentrations. Equivalent doses of these drugs were also injected into four polyvinylchloride jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the ECMO circuits and the controls over 24 hours and the concentrations of the study drugs were quantified using validated assays.

Results

Four hundred samples were analyzed. All study drugs, except meropenem, were chemically stable. The average drug recoveries from the ECMO circuits and the controls at 24 hours relative to baseline, respectively, were fentanyl 3% and 82%, morphine 103% and 97%, midazolam 13% and 100%, meropenem 20% and 42%, vancomycin 90% and 99%. There was a significant loss of fentanyl (p = 0.0005), midazolam (p = 0.01) and meropenem (p = 0.006) in the ECMO circuit at 24 hours. There was no significant circuit loss of vancomycin at 24 hours (p = 0.26).

Conclusions

Sequestration of drugs in the circuit has implications on both the choice and dosing of some drugs prescribed during ECMO. Sequestration of lipophilic drugs such as fentanyl and midazolam appears significant and may in part explain the increased dosing requirements of these drugs during ECMO. Meropenem sequestration is also problematic and these data support a more frequent administration during ECMO.