Log in | Register

Determinants of drug absorption in different ECMO circuitsOpen access

E. D. Wildschut| M. J. Ahsman| K. Allegaert| R. A. A. Mathot| D. Tibboel
Pediatric Original
Volume 36, Issue 12 / December , 2010

Pages 2109 - 2116

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.

Keywords

References

  1. Buck ML (2003) Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet 42:403–417
    • View reference on publisher's website
    • View reference on PubMed
  2. Mulla H, McCormack P, Lawson G, Firmin RK, Upton DR (2003) Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation. Anesthesiology 99:275–282
    • View reference on publisher's website
    • View reference on PubMed
  3. Peters JW, Anderson BJ, Simons SH, Uges DR, Tibboel D (2005) Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 31:257–263
  4. Mulla H, Pooboni S (2005) Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 60:265–275
    • View reference on publisher's website
    • View reference on PubMed
  5. Amaker RD, DiPiro JT, Bhatia J (1996) Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 40:1139–1142
    • View reference on PubMed
  6. Rayyan M, Allegaert K (2007) Pharmacotherapy during neonatal extracorporeal membrane oxygenation: toward an evidence-based approach. Crit Care 11:107
    • View reference on publisher's website
    • View reference on PubMed
  7. 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 15:21–26
    • View reference on PubMed
  8. 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 33:1018–1024
  9. 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 15:263–266
    • View reference on publisher's website
    • View reference on PubMed
  10. 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 27:51–56
    • View reference on PubMed
  11. Bhatt-Meht V, Annich G (2005) Sedative clearance during extracorporeal membrane oxygenation. Perfusion 20:309–315
    • View reference on publisher's website
    • View reference on PubMed
  12. 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 53:75–80
    • View reference on publisher's website
    • View reference on PubMed
  13. 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–D906
    • View reference on PubMed
  14. Rosen DA, Rosen KR, Silvasi DL (1990) In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth 4:332–335
    • View reference on publisher's website
    • View reference on PubMed
  15. Skacel M, Knott C, Reynolds F, Aps C (1986) Extracorporeal circuit sequestration of fentanyl and alfentanil. Br J Anaesth 58:947–949
    • View reference on publisher's website
    • View reference on PubMed
  16. 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):407–419
    • View reference on publisher's website
    • View reference on PubMed
  17. 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 61:11
    • View reference on publisher's website
  18. 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 34:2241–2247
  19. 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 32:1771–1776
    • View reference on publisher's website
    • View reference on PubMed
  20. 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:R48
    • View reference on publisher's website
    • View reference on PubMed
  21. Rosen DA, Rosen KR (1997) Elimination of drugs and toxins during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 11:337–340
    • View reference on publisher's website
    • View reference on PubMed
  22. 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 2:281–289
    • View reference on publisher's website
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement