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Antimicrobial Dosing during Extracorporeal Membrane Oxygenation

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Annual Update in Intensive Care and Emergency Medicine 2014

Part of the book series: Annual Update in Intensive Care and Emergency Medicine ((AUICEM,volume 2014))

Abstract

Extracorporeal membrane oxygenation (ECMO) is increasingly used to support cardiac and respiratory function in critically ill patients [1]. As in continuous renal replacement therapy (CRRT), antimicrobial dose adaptation during ECMO has been completely neglected for decades [2, 3]. However, ECMO has been shown to enhance the already profound physiologic derangements in critically ill patients, thereby significantly altering drug pharmacokinetics (PK) [4].

Common mechanisms that influence PK during ECMO are sequestration in the circuit, increased volume of distribution (Vd), decreased drug elimination and, in analogy with CRRT [5, 6], direct adsorption to the membrane [7]. Lipophilic highly protein-bound antimicrobials with a large Vd (e. g., voriconazole) are markedly sequestered in the circuit [4, 8–11]. In contrast, hydrophilic antimicrobials with a small Vd (e. g., β-lactams and glycopeptides) are more prone to hemodilution and direct adsorption by the membrane [4, 8–12].

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References

  1. Bartlett RH, Gattinoni L (2010) Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol 76:534–540

    CAS  PubMed  Google Scholar 

  2. Honore PM, Jacobs R, Spapen HD (2012) Use of antifungal drugs during continuous hemofiltration therapies. In: Vincent JL (ed) Annual Update in Intensive Care and Emergency Medicine. Springer, Heidelberg, pp 337–347

    Google Scholar 

  3. Maynar JM, Honore PM, Sanchez-Izquierdo JA, Herrera M, Spapen HD (2012) Handling RRT-related adverse effects in ICU patients: the Dialytrauma concept. Blood Purif 34:177–176

    Article  Google Scholar 

  4. Shekar K, Fraser JF, Smith MT, Roberts JA (2012) Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J Crit Care 27:e9–18

    Article  PubMed  Google Scholar 

  5. Honore PM, Jacobs R, Spapen HD (2013) Antibiotic Adsorption on CRRT Membranes. Relevance and impact on antibiotic dosing in critically ill patients. In: Vincent JL (ed) Annual Update in Intensive Care and Emergency Medicine. Springer, Heidelberg, pp 123–135

    Google Scholar 

  6. Honore PM, Jacobs R, Lochy S et al (2013) Acute respiratory muscle weakness and apnea in a critically ill patient induced by colistin neurotoxicity: key potential role of hemoadsorption elimination during continuous venovenous hemofiltration. Int J Nephrol Renovasc Dis 6:107–111

    Article  PubMed Central  PubMed  Google Scholar 

  7. Nakabayashi N, Iwasaki Y (2004) Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) as biomaterials. Biomed Mater Eng 14:345–354

    CAS  PubMed  Google Scholar 

  8. Shekar K, Mullany DV, Corley A et al (2012) Increased sedation requirements in patients receiving extracorporeal life support for respiratory and cardio-respiratory failure. Anaesth Intensive Care 40:648–655

    CAS  PubMed  Google Scholar 

  9. MacLaren G, Combes A, Bartlett RH (2012) Contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era. Intensive Care Med 38:210–220

    Article  PubMed  Google Scholar 

  10. Shekar K, Roberts JA, McDonald CI et al (2012) Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care 16:R194

    Article  PubMed  Google Scholar 

  11. Shekar K, Roberts JA, Ghassabian S et al (2013) Altered antibiotic pharmacokinetics during extracorporeal membrane oxygenation: cause for concern? J Antimicrob Chemother 68:726–727

    Article  CAS  PubMed  Google Scholar 

  12. Wildschut ED, Ahsman MJ, Allegaert K, Mathot RA, Tibboel D (2010) Determinants of drug absorption in different ECMO circuits. Intensive Care Med 36:2109–2116

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Mousavi S, Levcovich B, Mojtahedzadeh M (2011) A systematic review on pharmacokinetic changes in critically ill patients: role of extracorporeal membrane oxygenation. Daru 19:312–321

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Shekar K, Roberts JA, Welch S et al (2012) ASAP ECMO: Antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation: a multi-centre study to optimise drug therapy during ECMO. BMC Anesthesiol 12:29

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Muellenbach RM, Kredel M, Kranke P, Kunze E et al (2012) Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury. J Trauma Acute Care Surg 72:1444–1447

    PubMed  Google Scholar 

  16. Jamal JA, Economou CJ, Lipman J, Roberts JA (2012) Improving antibiotic dosing in special situations in the ICU: burns, renal replacement therapy and extracorporeal membrane oxygenation. Curr Opin Crit Care 18:460–471

    Article  PubMed  Google Scholar 

  17. Taccone FS, Laterre PF, Spapen H et al (2010) Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care 14:R53

    Article  PubMed  Google Scholar 

  18. Bělohlávek J, Springer D, Mlček M, et al (2013) Early vancomycin, amikacin and gentamicin concentrations in pulmonary artery and pulmonary tissue are not affected by VA ECMO (venoarterial extracorporeal membrane oxygenation) in a pig model of prolonged cardiac arrest. Pulm Pharmacol Ther 26:655–660

    Google Scholar 

  19. Lovering AM, Vickery CJ, Watkin DS et al (1995) The pharmacokinetics of meropenem in surgical patients with moderate or severe infections. J Antimicrob Chemother 36:165–172

    Article  CAS  PubMed  Google Scholar 

  20. Taccone FS, Laterre PF, Dugernier T et al (2010) Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care 14:R126

    Article  PubMed  Google Scholar 

  21. Roberts JA, Kirkpatrick CM, Roberts MS, Robertson TA, Dalley AJ, Lipman J (2009) Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 64:142–150

    Article  CAS  PubMed  Google Scholar 

  22. Jaruratanasirikul S, Sriwiriyajan S, Punyo J (2005) Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection. Antimicrob Agents Chemother 49:1337–1339

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Varghese JM, Roberts JA, Lipman J (2010) Pharmacokinetics and pharmacodynamics in critically ill patients. Curr Opin Anaesthesiol 23:472–478

    Article  PubMed  Google Scholar 

  24. Gonçalves-Pereira J, Póvoa P (2011) Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Crit Care 15:R206

    Article  PubMed  Google Scholar 

  25. Berthoin K, Le Duff CS, Marchand-Brynaert J, Carryn S, Tulkens PM (2010) Stability of meropenem and doripenem solutions for administration by continuous infusion. J Antimicrob Chemother 65:1073

    Article  CAS  PubMed  Google Scholar 

  26. Hsaiky L, Murray KP, Kokoska L, Desai N, Cha R (2013) Standard versus prolonged doripenem infusion for treatment of gram-negative infections. Ann Pharmacother 47:999–1006

    Article  PubMed  Google Scholar 

  27. Goncalves-Pereira J, Paiva JA (2013) Dose modulation: a new concept of antibiotic therapy in the critically ill patient ? J Crit Care 28:341–346

    Article  PubMed  Google Scholar 

  28. Roberts JA, Webb S, Paterson D, Ho KM, Lipman J (2009) A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med 37:2071–2078

    Article  CAS  PubMed  Google Scholar 

  29. Lorente L, Jimenez A, Martin MM et al (2009) Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents 33:464–468

    Article  CAS  PubMed  Google Scholar 

  30. Rafati MR, Rouini MR, Mojtahedzadeh M et al (2006) Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients. Int J Antimicrob Agents 28:122–127

    Article  CAS  PubMed  Google Scholar 

  31. Jehl F, Muller-Serieys C, de Larminat V, Monteil H, Bergogne-Berezin E (1994) Penetration of piperacillin-tazobactam into bronchial secretions after multiple doses to intensive care patients. Antimicrob Agents Chemother 38:2780–2784

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Boselli E, Breilh D, Cannesson M et al (2004) Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia. Intensive Care Med 30:976–979

    Article  PubMed  Google Scholar 

  33. Boselli E, Breilh D, Rimmelé T et al (2008) Alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to patients with ventilator-associated pneumonia. Crit Care Med 36:1500–1506

    Article  CAS  PubMed  Google Scholar 

  34. Mulla H, Pooboni S (2005) Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 60:265–275

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Beumier M, Roberts JA, Kabtouri H, et al (2013) A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy. J Antimicrob Chemother 68:2859–2865

    Google Scholar 

  36. Spapen HD, van Janssen Doorn K, Diltoer M et al (2011) Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. Ann Intensive Care 1:26

    Article  PubMed Central  PubMed  Google Scholar 

  37. Ulldemolins M, Roberts JA, Rello J et al (2011) The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill patients. Clin Pharmacokinet 50:99–110

    Article  CAS  PubMed  Google Scholar 

  38. Wolter K, Claus M, Wagner K, Fritschka E (1994) Teicoplanin pharmacokinetics and dosage recommendations in chronic hemodialysis patients and in patients undergoing continuous veno-venous hemodialysis. Clin Nephrol 42:389–397

    CAS  PubMed  Google Scholar 

  39. Matthews PC, Chue AL, Wyllie D et al (2014) Increased teicoplanin doses are associated with improved serum levels but not drug toxicity. J Infect 68:43–49

    Google Scholar 

  40. Matsumoto K, Kanazawa N, Watanabe E et al (2013) Development of initial loading procedure for teicoplanin in critically ill patients with severe infections. Biol Pharm Bull 36:1024–1026

    Article  CAS  PubMed  Google Scholar 

  41. Shiraishi Y, Okajima M, Sai Y, Miyamoto K, Inaba H (2012) Elimination of teicoplanin by adsorption to the filter membrane during haemodiafiltration: screening experiments for linezolid, teicoplanin and vancomycin followed by in vitro haemodiafiltration models for teicoplanin. Anaesth Intensive Care 40:442–449

    CAS  PubMed  Google Scholar 

  42. De Rosa FG, Corcione S, Baietto L et al (2013) Pharmacokinetics of linezolid during extracorporeal membrane oxygenation. Int J Antimicrob Agents 41:590–591

    Article  PubMed  Google Scholar 

  43. Veinstein A, Debouverie O, Gregoire N et al (2012) Lack of effect of extracorporeal membrane oxygenation on tigecycline pharmacokinetics. J Antimicrob Chemother 67:1047–1048

    Article  CAS  PubMed  Google Scholar 

  44. Muralidharan G, Micalizzi M, Speth J, Raible D, Troy S (2005) Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob Agents Chemother 44(49):220–229

    Article  Google Scholar 

  45. Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC (2013) Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother 57:1756–1762

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Markou N, Fousteri M, Markantonis SL et al (2012) Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study. J Antimicrob Chemother 67:2459–2462

    Article  CAS  PubMed  Google Scholar 

  47. Dudhani RV, Turnidge JD, Coulthard K et al (2010) Elucidation of the pharmacokinetic/pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob Agents Chemother 54:1117–1124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Mehta NM, Halwick DR, Dodson BL et al (2007) Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment. Intensive Care Med 33:1018–1024

    Article  CAS  PubMed  Google Scholar 

  49. Spriet I, Annaert P, Meersseman P et al (2009) Pharmacokinetics of caspofungin and voriconazole in critically ill patients during extracorporeal membrane oxygenation. J Antimicrob Chemother 63:767–770

    Article  CAS  PubMed  Google Scholar 

  50. Askenazi DJ, Selewski DT, Paden ML et al (2012) Renal replacement therapy in critically ill patients receiving extracorporeal membrane oxygenation. Clin. J Am Soc Nephrol 7:1328–1336

    Article  Google Scholar 

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Authors and Affiliations

  1. Intensive Care Dept, University Hospital, Vrije Universiteit Brussel, Brussels, Belgium

    P. M. Honoré, R. Jacobs & H.D. Spapen

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  1. P. M. Honoré
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  2. R. Jacobs
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  3. H.D. Spapen
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Correspondence to P. M. Honoré .

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  1. Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium

    Jean-Louis Vincent Prof.

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Honoré, P.M., Jacobs, R., Spapen, H. (2014). Antimicrobial Dosing during Extracorporeal Membrane Oxygenation. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2014. Annual Update in Intensive Care and Emergency Medicine, vol 2014. Springer, Cham. https://doi.org/10.1007/978-3-319-03746-2_4

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  • DOI: https://doi.org/10.1007/978-3-319-03746-2_4

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-03745-5

  • Online ISBN: 978-3-319-03746-2

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