Determinants of drug absorption in different ECMO circuits
Open Access
- 23 September 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Intensive Care Medicine
- Vol. 36 (12), 2109-2116
- https://doi.org/10.1007/s00134-010-2041-z
Abstract
The aim of this in vitro study was to evaluate potential determinants of drug loss in different ECMO circuits. Midazolam, morphine, fentanyl, paracetamol, cefazolin, meropenem and vancomycin were injected into three neonatal roller pump, two paediatric roller pump and two clinically used neonatal roller pump circuits, all with a silicone membrane, and two neonatal centrifugal pump circuits with polypropylene hollow-fibre membranes. Serial blood samples were taken from a post-oxygenator site. Drug recovery was calculated as the ratio between the determined and the theoretical maximum concentration. The latter was obtained by dividing dose by theoretical circuit volume. Average drug recoveries at 180 min in three neonatal silicone membrane roller pump circuits were midazolam 0.62%, morphine 23.9%, fentanyl 0.35%, paracetamol 34.0%, cefazolin 84.3%, meropenem 82.9% and vancomycin 67.8%. There was a significant correlation between the lipophilicity of the drug expressed as log P and the extent of drug absorption, p < 0.001. The recovery of midazolam and fentanyl in centrifugal pump circuits with hollow-fibre membrane oxygenator was significantly higher compared to neonatal roller pump circuits with silicone membranes: midazolam 63.4 versus 0.62%, fentanyl 33.8 versus 0.35%, p < 0.001. Oxygenator size and used circuits do not significantly affect drug losses. Significant absorption of drugs occurs in the ECMO circuit, correlating with increased lipophilicity of the drug. Centrifugal pump circuits with hollow-fibre membrane oxygenators show less absorption for all drugs, most pronounced for lipophilic drugs. These results suggest that pharmacokinetics and hence optimal doses of these drugs may be altered during ECMO.Keywords
This publication has 21 references indexed in Scilit:
- Population Pharmacokinetics of Midazolam and Its Metabolites during Venoarterial Extracorporeal Membrane Oxygenation in NeonatesClinical Pharmacokinetics, 2010
- Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison studyCritical Care, 2009
- Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in NeonatesAntimicrobial Agents and Chemotherapy, 2009
- DrugBank: a knowledgebase for drugs, drug actions and drug targetsNucleic Acids Research, 2007
- Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenationBritish Journal of Clinical Pharmacology, 2005
- Pharmacokinetic Changes During Extracorporeal Membrane OxygenationClinical Pharmacokinetics, 2003
- Effects of neonatal extracorporeal membrane oxygenation circuits on drug dispositionCurrent Therapeutic Research, 2000
- Preliminary Studies of the Effects of Extracorporeal Membrane Oxygenator on the Disposition of Common Pediatric DrugsTherapeutic Drug Monitoring, 1993
- In vitro variability in fentanyl absorption by different membrane oxygenatorsJournal of Cardiothoracic Anesthesia, 1990
- The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopentalJournal of Cardiothoracic Anesthesia, 1988