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Published in: Intensive Care Medicine 12/2010

Open Access 01-12-2010 | Pediatric Original

Determinants of drug absorption in different ECMO circuits

Authors: E. D. Wildschut, M. J. Ahsman, K. Allegaert, R. A. A. Mathot, D. Tibboel

Published in: Intensive Care Medicine | Issue 12/2010

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Abstract

Purpose

The aim of this in vitro study was to evaluate potential determinants of drug loss in different ECMO circuits.

Methods

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.

Results

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.

Conclusions

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.
Literature
1.
go back to reference Buck ML (2003) Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet 42:403–417CrossRefPubMed Buck ML (2003) Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet 42:403–417CrossRefPubMed
2.
go back to reference Mulla H, McCormack P, Lawson G, Firmin RK, Upton DR (2003) Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation. Anesthesiology 99:275–282CrossRefPubMed Mulla H, McCormack P, Lawson G, Firmin RK, Upton DR (2003) Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation. Anesthesiology 99:275–282CrossRefPubMed
3.
go back to reference Peters JW, Anderson BJ, Simons SH, Uges DR, Tibboel D (2005) Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 31:257–263CrossRefPubMed Peters JW, Anderson BJ, Simons SH, Uges DR, Tibboel D (2005) Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 31:257–263CrossRefPubMed
4.
go back to reference Mulla H, Pooboni S (2005) Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 60:265–275CrossRefPubMed Mulla H, Pooboni S (2005) Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 60:265–275CrossRefPubMed
5.
go back to reference Amaker RD, DiPiro JT, Bhatia J (1996) Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 40:1139–1142PubMed Amaker RD, DiPiro JT, Bhatia J (1996) Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 40:1139–1142PubMed
6.
go back to reference Rayyan M, Allegaert K (2007) Pharmacotherapy during neonatal extracorporeal membrane oxygenation: toward an evidence-based approach. Crit Care 11:107CrossRefPubMed Rayyan M, Allegaert K (2007) Pharmacotherapy during neonatal extracorporeal membrane oxygenation: toward an evidence-based approach. Crit Care 11:107CrossRefPubMed
7.
go back to reference Mulla H, Lawson G, von Anrep C, Burke M, Upton D, Firmin R, Killer H (2000) In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion 15:21–26PubMed Mulla H, Lawson G, von Anrep C, Burke M, Upton D, Firmin R, Killer H (2000) In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion 15:21–26PubMed
8.
go back to reference Mehta NM, Halwick DR, Dodson BL, Thompson JE, Arnold JH (2007) Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment. Intensive Care Med 33:1018–1024CrossRefPubMed Mehta NM, Halwick DR, Dodson BL, Thompson JE, Arnold JH (2007) Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment. Intensive Care Med 33:1018–1024CrossRefPubMed
9.
go back to reference Dagan O, Klein J, Gruenwald C, Bohn D, Barker G, Koren G (1993) Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs. Ther Drug Monit 15:263–266CrossRefPubMed Dagan O, Klein J, Gruenwald C, Bohn D, Barker G, Koren G (1993) Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs. Ther Drug Monit 15:263–266CrossRefPubMed
10.
go back to reference Koren G, Crean P, Klein J, Goresky G, Villamater J, MacLeod SM (1984) Sequestration of fentanyl by the cardiopulmonary bypass (CPBP). Eur J Clin Pharmacol 27:51–56PubMed Koren G, Crean P, Klein J, Goresky G, Villamater J, MacLeod SM (1984) Sequestration of fentanyl by the cardiopulmonary bypass (CPBP). Eur J Clin Pharmacol 27:51–56PubMed
11.
go back to reference Bhatt-Meht V, Annich G (2005) Sedative clearance during extracorporeal membrane oxygenation. Perfusion 20:309–315CrossRefPubMed Bhatt-Meht V, Annich G (2005) Sedative clearance during extracorporeal membrane oxygenation. Perfusion 20:309–315CrossRefPubMed
12.
go back to reference Ahsman MJ, Wildschut ED, Tibboel D, Mathot RA (2009) Microanalysis of beta-lactam antibiotics and vancomycin in plasma for pharmacokinetic studies in neonates. Antimicrob Agents Chemother 53:75–80CrossRefPubMed Ahsman MJ, Wildschut ED, Tibboel D, Mathot RA (2009) Microanalysis of beta-lactam antibiotics and vancomycin in plasma for pharmacokinetic studies in neonates. Antimicrob Agents Chemother 53:75–80CrossRefPubMed
13.
go back to reference Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M, Res NA (2008) DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res 36(Database issue):D901–D906PubMed Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M, Res NA (2008) DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res 36(Database issue):D901–D906PubMed
14.
go back to reference Rosen DA, Rosen KR, Silvasi DL (1990) In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth 4:332–335CrossRefPubMed Rosen DA, Rosen KR, Silvasi DL (1990) In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth 4:332–335CrossRefPubMed
15.
go back to reference Skacel M, Knott C, Reynolds F, Aps C (1986) Extracorporeal circuit sequestration of fentanyl and alfentanil. Br J Anaesth 58:947–949CrossRefPubMed Skacel M, Knott C, Reynolds F, Aps C (1986) Extracorporeal circuit sequestration of fentanyl and alfentanil. Br J Anaesth 58:947–949CrossRefPubMed
16.
go back to reference Ahsman MJ, Hanekamp M, Wildschut ED, Tibboel D, Mathot RAA (2010) Population pharmacokinetics of midazolam and metabolites during venoarterial extracorporeal membrane oxygenation in neonates. Clin Pharmacokinet 49(6):407–419CrossRefPubMed Ahsman MJ, Hanekamp M, Wildschut ED, Tibboel D, Mathot RAA (2010) Population pharmacokinetics of midazolam and metabolites during venoarterial extracorporeal membrane oxygenation in neonates. Clin Pharmacokinet 49(6):407–419CrossRefPubMed
17.
go back to reference Mulla HLG, Woodland ED, Peek GJ, Killer H, Firmin RK, Upton DR (2000) Effects of neonatal extracorporeal membrane oxygenation circuits on drug disposition. Curr Ther Res 61:11CrossRef Mulla HLG, Woodland ED, Peek GJ, Killer H, Firmin RK, Upton DR (2000) Effects of neonatal extracorporeal membrane oxygenation circuits on drug disposition. Curr Ther Res 61:11CrossRef
18.
go back to reference Hoover NG, Heard M, Reid C, Wagoner S, Rogers K, Foland J, Paden ML, Fortenberry JD (2008) Enhanced fluid management with continuous venovenous hemofiltration in pediatric respiratory failure patients receiving extracorporeal membrane oxygenation support. Intensive Care Med 34:2241–2247CrossRefPubMed Hoover NG, Heard M, Reid C, Wagoner S, Rogers K, Foland J, Paden ML, Fortenberry JD (2008) Enhanced fluid management with continuous venovenous hemofiltration in pediatric respiratory failure patients receiving extracorporeal membrane oxygenation support. Intensive Care Med 34:2241–2247CrossRefPubMed
19.
go back to reference Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard ML, Rogers K, Reid C, Tanner AJ, Easley KA (2004) Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med 32:1771–1776CrossRefPubMed Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard ML, Rogers K, Reid C, Tanner AJ, Easley KA (2004) Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med 32:1771–1776CrossRefPubMed
20.
go back to reference Blijdorp KCK, Wildschut ED, Gischler SJ, Houmes RJ, Wolff ED, Tibboel D (2009) Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison study. Crit Care 13:R48CrossRefPubMed Blijdorp KCK, Wildschut ED, Gischler SJ, Houmes RJ, Wolff ED, Tibboel D (2009) Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison study. Crit Care 13:R48CrossRefPubMed
21.
go back to reference Rosen DA, Rosen KR (1997) Elimination of drugs and toxins during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 11:337–340CrossRefPubMed Rosen DA, Rosen KR (1997) Elimination of drugs and toxins during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 11:337–340CrossRefPubMed
22.
go back to reference Bjorksten AR, Crankshaw DP, Morgan DJ, Prideaux PR (1988) The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopental. J Cardiothorac Anesth 2:281–289CrossRefPubMed Bjorksten AR, Crankshaw DP, Morgan DJ, Prideaux PR (1988) The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopental. J Cardiothorac Anesth 2:281–289CrossRefPubMed
Metadata
Title
Determinants of drug absorption in different ECMO circuits
Authors
E. D. Wildschut
M. J. Ahsman
K. Allegaert
R. A. A. Mathot
D. Tibboel
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 12/2010
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-010-2041-z

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