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Published in: Intensive Care Medicine 6/2007

01-06-2007 | Pediatric Original

Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment

Authors: Nilesh M. Mehta, David R. Halwick, Brenda L. Dodson, John E. Thompson, John H. Arnold

Published in: Intensive Care Medicine | Issue 6/2007

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Abstract

Objective

Using an ex vivo simulation model we set out to estimate the amount of drug lost due to sequestration within the extracorporeal circuit over time.

Design

Simulated closed-loop extracorporeal membrane oxygenation (ECMO) circuits were prepared using a 1.5-m2 silicone membrane oxygenator. Group A consisted of heparin, dopamine, ampicillin, vancomycin, phenobarbital and fentanyl. Group B consisted of epinephrine, cefazolin, hydrocortisone, fosphenytoin and morphine. Drugs were tested in crystalloid and blood-primed circuits. After administration of a one-time dose of drugs in the priming fluid, baseline drug concentrations were obtained (P0). A simultaneous specimen was stored for stability testing at 24 h (P4). Serial post-membrane drug concentrations were then obtained at 30 min (P1), 3 h (P2) and 24 h (P3) from circuit fluid.

Measurements and results

One hundred and one samples were analyzed. At the end of 24 h in crystalloid-primed circuits, 71.8% of ampicillin, 96.7% of epinephrine, 17.6% of fosphenytoin, 33.3% of heparin, 17.5% of morphine and 87% of fentanyl was lost. At the end of 24 h in blood-primed extracorporeal circuits, 15.4% of ampicillin, 21% of cefazolin, 71% of voriconazole, 31.4% of fosphenytoin, 53.3% of heparin and 100% of fentanyl was lost. There was a significant decrease in overall drug concentrations from 30 min to 24 h for both crystalloid-primed circuits (p = 0.023) and blood-primed circuits (p = 0.04).

Conclusions

Our ex vivo study demonstrates serial losses of several drugs commonly used during ECMO therapy. Therapeutic concentrations of fentanyl, voriconazole, antimicrobials and heparin cannot be guaranteed in patients on ECMO.
Literature
1.
go back to reference Green TP, Timmons OD, Fackler JC, Moler FW, Thompson AE, Sweeney MF (1996) The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Crit Care Med 24:323–329PubMedCrossRef Green TP, Timmons OD, Fackler JC, Moler FW, Thompson AE, Sweeney MF (1996) The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Crit Care Med 24:323–329PubMedCrossRef
2.
go back to reference Lequier L (2004) Extracorporeal life support in pediatric and neonatal critical care: a review. J Intensive Care Med 19:243–258PubMedCrossRef Lequier L (2004) Extracorporeal life support in pediatric and neonatal critical care: a review. J Intensive Care Med 19:243–258PubMedCrossRef
3.
go back to reference Mulla H, Lawson G, von Anrep C, Burke MD, Upton DU, Firmin RK, 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 MD, Upton DU, Firmin RK, Killer H (2000) In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion 15:21–26PubMed
4.
go back to reference Buck ML (2003) Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet 42:403–417PubMedCrossRef Buck ML (2003) Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet 42:403–417PubMedCrossRef
5.
go back to reference Mehta NM, Halwick DR, Dodson BL, Thompson JE, Arnold JH (2006). Pharmacokinetic considerations during extracorporeal membrane oxygenation – results from an in vitro simulation model. Paper presented at: American Thoracic Society, International Conference (San Diego, CA, USA) Mehta NM, Halwick DR, Dodson BL, Thompson JE, Arnold JH (2006). Pharmacokinetic considerations during extracorporeal membrane oxygenation – results from an in vitro simulation model. Paper presented at: American Thoracic Society, International Conference (San Diego, CA, USA)
6.
go back to reference Pennick GJ, Clark M, Sutton DA, Rinaldi MG (2003) Development and validation of a high-performance liquid chromatography assay for voriconazole. Antimicrob Agents Chemother 47:2348–2350PubMedCrossRef Pennick GJ, Clark M, Sutton DA, Rinaldi MG (2003) Development and validation of a high-performance liquid chromatography assay for voriconazole. Antimicrob Agents Chemother 47:2348–2350PubMedCrossRef
7.
go back to reference Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J (2006) DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 34:D668–672PubMedCrossRef Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J (2006) DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 34:D668–672PubMedCrossRef
8.
go back to reference Ball D, Tisocki K (1999) PVC bags considerably reduce availability of diazepam. Cent Afr J Med 45:105PubMed Ball D, Tisocki K (1999) PVC bags considerably reduce availability of diazepam. Cent Afr J Med 45:105PubMed
9.
go back to reference Mahomed K, Nyamurera T, Tarumbwa A (1998) PVC bags considerably reduce availability of diazepam. Cent Afr J Med 44:171–173PubMed Mahomed K, Nyamurera T, Tarumbwa A (1998) PVC bags considerably reduce availability of diazepam. Cent Afr J Med 44:171–173PubMed
10.
go back to reference Airaudo CB, Gayte-Sorbier A, Bianchi C, Verdier M (1993) Interactions between six psychotherapeutic drugs and plastic containers. Influence of plastic material and infusion solutions. Int J Clin Pharmacol Ther Toxicol 31:261–266PubMed Airaudo CB, Gayte-Sorbier A, Bianchi C, Verdier M (1993) Interactions between six psychotherapeutic drugs and plastic containers. Influence of plastic material and infusion solutions. Int J Clin Pharmacol Ther Toxicol 31:261–266PubMed
11.
go back to reference Martens HJ, De Goede PN, Van Loenen AC (1990) Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers. Am J Hosp Pharm 47:369–373PubMed Martens HJ, De Goede PN, Van Loenen AC (1990) Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers. Am J Hosp Pharm 47:369–373PubMed
12.
go back to reference Coffin SE, Bell LM, Manning M, Polin R (1997) Nosocomial infections in neonates receiving extracorporeal membrane oxygenation. Infect Control Hosp Epidemiol 18:93–96PubMedCrossRef Coffin SE, Bell LM, Manning M, Polin R (1997) Nosocomial infections in neonates receiving extracorporeal membrane oxygenation. Infect Control Hosp Epidemiol 18:93–96PubMedCrossRef
13.
go back to reference Burket JS, Bartlett RH, Vander Hyde K, Chenoweth CE (1999) Nosocomial infections in adult patients undergoing extracorporeal membrane oxygenation. Clin Infect Dis 28:828–833PubMed Burket JS, Bartlett RH, Vander Hyde K, Chenoweth CE (1999) Nosocomial infections in adult patients undergoing extracorporeal membrane oxygenation. Clin Infect Dis 28:828–833PubMed
14.
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
15.
go back to reference Bhatt-Mehta V, Johnson CE, Schumacher RE (1992) Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 12:28–32PubMed Bhatt-Mehta V, Johnson CE, Schumacher RE (1992) Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 12:28–32PubMed
16.
go back to reference Buck ML (1998) Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 18:1082–1086PubMed Buck ML (1998) Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 18:1082–1086PubMed
17.
go back to reference Moller JC, Gilman JT, Kearns GL, Sussmane JB, Raszynski A, Wolfsdorf J, Reed MD (1992) Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep. Crit Care Med 20:1454–1458PubMedCrossRef Moller JC, Gilman JT, Kearns GL, Sussmane JB, Raszynski A, Wolfsdorf J, Reed MD (1992) Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep. Crit Care Med 20:1454–1458PubMedCrossRef
18.
go back to reference Southgate WM, DiPiro JT, Robertson AF (1989) Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother 33:817–819PubMed Southgate WM, DiPiro JT, Robertson AF (1989) Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother 33:817–819PubMed
19.
go back to reference Wyatt RG, Okamoto GA, Feigin RD (1972) Stability of antibiotics in parenteral solutions. Pediatrics 49:22–29PubMed Wyatt RG, Okamoto GA, Feigin RD (1972) Stability of antibiotics in parenteral solutions. Pediatrics 49:22–29PubMed
20.
go back to reference Shanley CJ, Hirschl RB, Schumacher RE, Overbeck MC, Delosh TN, Chapman RA, Coran AG, Bartlett RH (1994) Extracorporeal life support for neonatal respiratory failure. A 20-year experience. Ann Surg 220:269–280; discussion 281–282PubMedCrossRef Shanley CJ, Hirschl RB, Schumacher RE, Overbeck MC, Delosh TN, Chapman RA, Coran AG, Bartlett RH (1994) Extracorporeal life support for neonatal respiratory failure. A 20-year experience. Ann Surg 220:269–280; discussion 281–282PubMedCrossRef
21.
go back to reference Elliott ES, Buck ML (1999) Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation. Ann Pharmacother 33:419–422PubMedCrossRef Elliott ES, Buck ML (1999) Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation. Ann Pharmacother 33:419–422PubMedCrossRef
22.
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 15:263–266PubMedCrossRef 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 15:263–266PubMedCrossRef
23.
go back to reference DeBerry BB, Lynch JE, Chernin JM, Zwischenberger JB, Chung DH (2005) A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation. Perfusion 20:139–143PubMedCrossRef DeBerry BB, Lynch JE, Chernin JM, Zwischenberger JB, Chung DH (2005) A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation. Perfusion 20:139–143PubMedCrossRef
24.
go back to reference Hynynen M (1987) Binding of fentanyl and alfentanil to the extracorporeal circuit. Acta Anaesthesiol Scand 31:706–710PubMedCrossRef Hynynen M (1987) Binding of fentanyl and alfentanil to the extracorporeal circuit. Acta Anaesthesiol Scand 31:706–710PubMedCrossRef
25.
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
26.
go back to reference Arnold JH, Truog RD, Orav EJ, Scavone JM, Hershenson MB (1990) Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 73:1136–1140PubMedCrossRef Arnold JH, Truog RD, Orav EJ, Scavone JM, Hershenson MB (1990) Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 73:1136–1140PubMedCrossRef
27.
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 31:257–263PubMedCrossRef Peters JW, Anderson BJ, Simons SH, Uges DR, Tibboel D (2005) Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 31:257–263PubMedCrossRef
28.
go back to reference Geiduschek JM, Lynn AM, Bratton SL, Sanders JC, Levy FH, Haberkern CM, O'Rourke PP (1997) Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation. Crit Care Med 25:360–364PubMedCrossRef Geiduschek JM, Lynn AM, Bratton SL, Sanders JC, Levy FH, Haberkern CM, O'Rourke PP (1997) Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation. Crit Care Med 25:360–364PubMedCrossRef
29.
go back to reference Rosen DA, Rosen KR, Silvasi DL (1990) In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth 4:332–335PubMedCrossRef Rosen DA, Rosen KR, Silvasi DL (1990) In vitro variability in fentanyl absorption by different membrane oxygenators. J Cardiothorac Anesth 4:332–335PubMedCrossRef
30.
go back to reference Grassi M, Coceani N, Magarotto L (2002) Modelling partitioning of sparingly soluble drugs in a two-phase liquid system. Int J Pharm 239:157–169PubMedCrossRef Grassi M, Coceani N, Magarotto L (2002) Modelling partitioning of sparingly soluble drugs in a two-phase liquid system. Int J Pharm 239:157–169PubMedCrossRef
31.
go back to reference Agus MS, Jaksic T (2004) Critically low hormone and catecholamine concentrations in the primed extracorporeal life support circuit. Asaio J 50:65–67PubMedCrossRef Agus MS, Jaksic T (2004) Critically low hormone and catecholamine concentrations in the primed extracorporeal life support circuit. Asaio J 50:65–67PubMedCrossRef
Metadata
Title
Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment
Authors
Nilesh M. Mehta
David R. Halwick
Brenda L. Dodson
John E. Thompson
John H. Arnold
Publication date
01-06-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 6/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0606-2

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