Introduction: Lipophilic drugs are shown to be degraded/sequestered in extracorporeal membrane oxygenation (ECMO) circuits. However, the circuit behaviour of protein bound drugs is not fully elucidated. Study objectives: This ex vivo experiment aimed to investigate the disposition of protein bound drugs in ECMO circuits. Methods: Four identical ECMO circuits comprising centrifugal pumps and polymethylpentene oxygenators were primed with crystalloid, albumin and fresh human whole blood and maintained at physiological conditions for 24 hours. After baseline sampling, known quantities of study drugs (ceftriaxone, ciprofloxacin, linezolid, fluconazole, caspofungin and thiopentone) were injected into the circuit. 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 controls and the ECMO circuits over 24 hours and the concentrations of the study drugs were quantified using validated chromatographic assays. Results: Four hundred and eighty samples were analysed. All of the study drugs were stable in controls (100% recovery at 24 hours). The mean total plasma protein and albumin concentration in the circuit were 33± 2.5 g/L and 25±0.9 g/L respectively. The average drug recoveries from the ECMO circuits at 24 hours respectively were ceftriaxone 80%, ciprofloxacin 96 %, linezolid 91 %, fluconazole 91%, caspofungin 56 % and thiopentone 12%. There was a significant reduction of ceftriaxone (p=0.01), caspofungin (p=0.01) and thiopentone (p <0.008) concentrations in the ECMO circuit at 24 hours. Circuit drug recovery correlated with degree of protein binding of drugs studied (Pearson r= -0.71, p < 0.05). Conclusion(s): Protein bound drugs may be significantly degraded/sequestered in ECMO circuits. The absence of data on unbound concentrations for these drugs limits any strong conclusions. Pending future clinical population PK studies, therapeutic drug monitoring should be considered for highly protein bound drugs where possible. Acknowledgements: This study was supported in part by funding provided by the National Health and Medical Research Council, the Australian and New Zealand College of Anaesthetists, the Intensive Care Foundation, The Prince Charles Hospital Foundation and the Australian Red Cross Blood Service (the Blood Service) and Australian governments that fully fund the Blood Service for the provision of blood products and services to the Australian community. We thank Ms. Suzie Parker-Scott for antibiotic drug assays.
40th Australian and New Zealand Intensive Care Society (ANZICS)/Australian College of Critical Care Nurses Annual (ACCCN) Scientific Meeting, Melbourne, Australia 9-11 October 2014
Anaesthesia and Intensive Care / Vol. 43, No. 2, pp.266