Extracorporeal Membrane Oxygenation and Drug Clearance

  • Peter D. Wearden
  • Victor O. Morell
  • Ricardo Munoz

The prolonged use of extracorporeal membrane oxygenation (ECMO) in the pediatric, and particularly neonatal, population to support patients for days to weeks has become increasingly commonplace over the past two decades. Along with little advancement in the underlying technology, there has been a relative paucity of research into the effects of ECMO on drug metabolism and elimination in children. By its very nature, ECMO is used in the most critically ill children, those who are often already receiving maximal pharmacological support with multiple vasoactive agents to improve their circulation. High doses of sedatives and muscle relaxants are common adjuncts to the management of the child on ECMO. The increased risk of infection requires the use of prophylactic or therapeutic antibiotics, and diuretics are frequently used to maintain fluid balance. Unlike most patients in the intensive care unit (ICU) setting, the successful use of ECMO generally requires full anticoagulation with heparin. This chapter reviews the general ways in which ECMO may affect drug clearance, and summarizes specific information regarding selected drugs that are used frequently in clinical practice.


Pulsatile Flow Extracorporeal Membrane Oxygenation ECMO Support Neonatal Abstinence Syndrome Drug Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Vrancken SL, Heijst, AF, Zegers M, et al. Influence of volume replacement with colloids versus crystalloids in neonates on venoarterial extracorporeal membrane oxygenation on fluid retention, fluid balance, and ECMO runtime. ASAIO J 2005; 51: 808–812.PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson HL, Coran AG, Drongowski RA, et al. Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation. J Pediatr Surg 1992; 27: 1003–1008.PubMedCrossRefGoogle Scholar
  3. 3.
    Kazzi NJ, Schwartz CA, Palder SB, et al. Effect of extracorporeal membrane oxygenation on body water content and distribution in lambs. ASAIO Transactions 1990; 36: 817–820.PubMedGoogle Scholar
  4. 4.
    Rosen DA, Rosen KR, Leong P. Uptake of lorazepam and midazolam by the Scimed membrane oxygenator. Anesthesiology 1990; 73: A474.Google Scholar
  5. 5.
    Dagan O, Klein J, Greunwald C, et al. Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs. Ther Drug Monit 1993; 15: 233–236.CrossRefGoogle Scholar
  6. 6.
    Mulla H, Lawson G, von Anrep C, et al. In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion 2000; 15: 21–26.PubMedGoogle Scholar
  7. 7.
    Hoie EB, Hall MC, Schaff LJ. Effects of injection site and flow rate on the distribution of injected solutions in an extracorporeal membrane oxygenation circuit. Am J Hosp Pharm 1993; 50: 1902–1906.PubMedGoogle Scholar
  8. 8.
    Shevde, K, DuBois WJ. Pro: pulsatile flow is preferable to nonpulsatile flow during cardiopulmonary bypass. J Cardiothorac Anesth 1987; 1: 165–168.PubMedCrossRefGoogle Scholar
  9. 9.
    Mavroudis C: To pulse or not to pulse. Ann Thorac Surg 1978, 25: 259–271.PubMedCrossRefGoogle Scholar
  10. 10.
    Hynynen M, Olkkola KT, Naveri E, et al. Thiopentone pharmacokinetics during cardiopulmonary bypass with a nonpulsatile or pulsatile flow. Acta Anaesthesiol Scand 1989; 33:554–560.PubMedCrossRefGoogle Scholar
  11. 11.
    Bartlett RH. Extracorporeal life support for cardiopulmonary failure. Curr Prob Surg 1990; 27: 621–705.CrossRefGoogle Scholar
  12. 12.
    Bentley JB, Conahan TJ III, Cork RC. Fentanyl sequestration in the lungs during cardiopulmonary bypass. Clin Pharmacol Ther 1983; 34: 703–706.PubMedGoogle Scholar
  13. 13.
    Green PT, Isham-Schopf B, Irmiter JR, et al. Inactivation of heparin during extracorporeal circulation in infants. Clin Pharmacol Ther 1990; 48: 148–153.PubMedGoogle Scholar
  14. 14.
    Southgate WM, DiPiro JT, Robertson AF. Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother 1989; 33: 817–819.PubMedGoogle Scholar
  15. 15.
    Cohen P, Collart L, Prober CG, et al. Gentamicin pharmacokinetics in neonates undergoing extracorporeal membrane oxygenation. Pediatr Infect Dis J 1990; 9: 562–566.PubMedCrossRefGoogle Scholar
  16. 16.
    Dodge WF, Jeliffe RW, Zwichenberger JB, et al. Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. Ther Drug Monit 1994; 16:552–559.PubMedCrossRefGoogle Scholar
  17. 17.
    Bhatt-Metta V, Johnson CE, Schumacher RE. Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 1992; 12: 28–32.Google Scholar
  18. 18.
    Munzenberger PJ, Massoud N. Pharmacokinetics of gentamicin in neonatal patients supported with extracorporeal membrane oxygenation. ASAIO Transactions 1991; 37: 16–18.PubMedCrossRefGoogle Scholar
  19. 19.
    Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy in neonates. Clin Pharmacokinet 2003; 42: 403–417.PubMedCrossRefGoogle Scholar
  20. 20.
    Hoie EB, Swigart SA, Leuschen MP, et al. Vancomycin pharmacokinetics in patients undergoing extracorporeal membrane oxygenation. Clin Pharm 1990; 9: 711–715.PubMedGoogle Scholar
  21. 21.
    Amaker RD, DiPiro JT, Bhatia J. Pharmacokinetics in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 1996; 40: 1139–1142.PubMedGoogle Scholar
  22. 22.
    Buck ML. Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 1998; 18: 1082–1086.PubMedGoogle Scholar
  23. 23.
    Mulla H, Pooboni S. Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 2005; 60: 265–275.PubMedCrossRefGoogle Scholar
  24. 24.
    Wells TG, Fasules JW, Taylor BJ, et al. Pharmacokinetics and pharmacodynamics of bumetanide in neonates treated with extracorporeal membrane oxygenation. J Pediatr 1992; 121: 974–980.PubMedCrossRefGoogle Scholar
  25. 25.
    Scala JL, Jew RK, Poon CY, et al. In vitro analysis of furosemide disposition during extracorporeal membrane oxygenation (ECMO) [abstract]. Pediatr Res 1996; 39: 78A.CrossRefGoogle Scholar
  26. 26.
    Wells TG, Heulitt M, Taylor BJ, et al. Pharmacokinetics and pharmacodynamics of ranitidine in neonates treated with extracorporeal membrane oxygenation. J Clin Pharmacol 1998; 38: 402–407.PubMedGoogle Scholar
  27. 27.
    Dasta JF, Jacobi J, Wu LS, et al. Loss of nitroglycerin in the cardiopulmonary bypass apparatus. Crit Care Med 1983; 11: 50–52.PubMedCrossRefGoogle Scholar
  28. 28.
    Williams GD, Sorensen GK, Oakes R, et al. Amrinone loading during cardiopulmonary bypass in neonates, infants and children. J Cardiothorac Vasc Anesth 1995; 9: 278–282.PubMedCrossRefGoogle Scholar
  29. 29.
    Bailey JM, Levy JH, Kikura M, et al. Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery. Anesthesiology 1994; 81: 616–622.PubMedCrossRefGoogle Scholar
  30. 30.
    Bogaert WA, Herregods LL, Mortierr EP. Cardiopulmonary bypass and pharmacokinetics of drugs. Clin Pharmacokinet 1989; 17: 10–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Weekes LM, Keneally JP, Goonetillek PH, Ramzan IM. Pharmacokinetics of alcuronium in children with acyanotic and cyanotic cardiac disease undergoing cardiopulmonary bypass surgery. Paediatr Anaesth 1995; 5: 369–374.PubMedCrossRefGoogle Scholar
  32. 32.
    Caron E, Maguire DP. Current management of pain, sedation and narcotic physical dependency of the infant on ECMO. J Perinat Neonatal Nurs 1990; 4: 63–74.PubMedGoogle Scholar
  33. 33.
    Arnold JH, Truog RD, Orav EJ, et al. Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 1990; 73: 1136–1140.PubMedCrossRefGoogle Scholar
  34. 34.
    Arnold JH, Truog RD, Scavone JM, et al. Changes in pharmacodynamic response to fentanyl in neonates during continuous infusion. J Pediatr 1991; 119: 639–643.PubMedCrossRefGoogle Scholar
  35. 35.
    Burda G, Trittenwein G. Issues of pharmacology in pediatric cardiac extracorporeal membrane oxygenation with special reference to analgesia and sedation. Artif Organs 1999; 23: 1015–1019.PubMedCrossRefGoogle Scholar
  36. 36.
    Franck LS, Vilardi J, Durand D, et al. Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation. Am J Crit Care 1998; 7: 364–369.PubMedGoogle Scholar
  37. 37.
    Bhatt-Mehta V, Annich G. Sedative clearance during extracorporeal membrane oxygenation. Perfusion, 2005; 20: 309–315.CrossRefGoogle Scholar
  38. 38.
    Dagan O, Klein J, Bohn D, et al. Effects of extracorporeal membrane oxygenation on morphine pharmacokinetics in infants. Crit Care Med 1994; 22: 1099–1101.PubMedCrossRefGoogle Scholar
  39. 39.
    Rosen DA, Rosen KR. A comparison of fentanyl uptake by three different membrane oxygenators. Anesthesiology 1986, 65: A128.Google Scholar
  40. 40.
    Koren G, Crean P, Klein J, et al. Sequestration of fentanyl by the cardiopulmonary bypass. Eur J Clin Pharmacol 1984; 27: 51–56.PubMedGoogle Scholar
  41. 41.
    Hynynen M. Binding of fentanyl and alfentanil to the extracorporeal circuit. Acta Anaesthesiol Scand 1987; 31: 706–710.PubMedCrossRefGoogle Scholar
  42. 42.
    Leuschen MP, Willett LD, Hoie EB, et al. Plasma fentanyl levels in infants undergoing extracorporeal membrane oxygenation. J Thorac Cardiovasc Surg 1993; 105: 885–891.PubMedGoogle Scholar
  43. 43.
    Rosen DA, Rosen KR. Midazolam for sedation in the pediatric intensive care unit. Intens Care Med 1991; 17: S15–19.CrossRefGoogle Scholar
  44. 44.
    Mulla H, Lawson G, Peek GJ, et al. Plasma concentrations of midazolam in neonates receiving extracorporeal membrane oxygenation. ASAIO J 2003; 49: 41–47.PubMedCrossRefGoogle Scholar
  45. 45.
    Mulla H, McCormack P, Lawson G, et al. Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation. Anesthesiology 2003; 99: 275–282.PubMedCrossRefGoogle Scholar
  46. 46.
    Hynynen M, Hammaren E, Rosenberg PH. Propofol sequestration within the extracorporeal circuit. Can J Anaesth 1994; 41: 583–588.PubMedCrossRefGoogle Scholar
  47. 47.
    Marx C, et al. Investigation of increased phenobarbital dose requirement for newborn infants on ECMO. In vitro adsorption in ECMO circuit. Pharmacotherapy 1991; 11: 270.Google Scholar
  48. 48.
    Elliot ES, Buck ML. Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation. Ann Pharmacother, 1999; 33: 419–422.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2008

Authors and Affiliations

  • Peter D. Wearden
    • 1
  • Victor O. Morell
    • 1
  • Ricardo Munoz
    • 2
  1. 1.Department of Cardiothoracic SurgeryChildren's Hospital of PittsburghPittsburghUSA
  2. 2.Critical Care Medicine, Pediatrics and SurgeryChildren's Hospital of Pittsburgh of UPMCPittsburghUSA

Personalised recommendations