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Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Adults During Extracorporeal Membrane Oxygenation: A Systematic Review

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Abstract

Purpose

Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for antimicrobial dosing adjustments in patients requiring extracorporporeal membrane oxygenation (ECMO) therapy. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill adult patients requiring ECMO.

Methods

Medline, EMBASE, Global Health, and All EBM Reviews databases were searched. Grey literature was examined. All studies reporting PK/PD parameters of antimicrobials in critically ill adults treated with ECMO were included, except for case reports and congress abstracts. Ex vivo studies were included. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently abstract data and evaluate methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK guidelines. Patients’ and studies’ characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Dosing recommendations were formulated based on data from controlled studies.

Results

Thirty-two clinical studies were included; most were observational and uncontrolled. Fourteen ex vivo studies were analysed. Information on patient characteristics and co-treatments was often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the studied drugs. Few dosing recommendations could be formulated given the lack of good quality data.

Conclusion

Limited data exist on the PK/PD of antimicrobials during ECMO therapy. Rigorously designed and well powered populational PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring ECMO support.

PROSPERO Registration Number

CRD42018099992 (Registered: July 24th 2018).

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Author notes

  1. Gordan Samoukovic and David R. Williamson contributed equally to this article.

Authors and Affiliations

  1. Department of Pharmacy, McGill University Health Centre, 1001 Boul. DĂ©carie, Local C-RC 6004, Montreal, QC, H4A 3J1, Canada

    Marc-Alexandre Duceppe, Anh Thu Do & Ni Ruo

  2. Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada

    Salmaan Kanji

  3. Faculty of Medicine, University of Ottawa, Ottawa, Canada

    Salmaan Kanji

  4. Faculté de Pharmacie, Université de Montréal, Montreal, Canada

    Salmaan Kanji & David R. Williamson

  5. Department of Medicine, Division of Critical Care, Hôpital du Sacré-Coeur de Montréal Research Centre, Montreal, Canada

    Yiorgos Alexandros Cavayas & Martin Albert

  6. Department of Surgery, Division of Critical Care, Montreal Heart Institute, Montreal, Canada

    Yiorgos Alexandros Cavayas & Martin Albert

  7. Département de Médecine, Faculté de Médecine, Université de Montréal, Montreal, Canada

    Yiorgos Alexandros Cavayas & Martin Albert

  8. Department of Medicine, Division of Cardiology, Centre Hospitalier de l’Université de Montréal, Montreal, Canada

    Maxime Robert-Halabi

  9. Department of Pediatrics, Division of Pediatric Critical Care, McGill University Health Centre, Montreal, Canada

    Samara Zavalkoff

  10. Faculty of Medicine, McGill University, Montreal, Canada

    Samara Zavalkoff & Gordan Samoukovic

  11. Bibliothèque de la santé, Université de Montréal, Montreal, Canada

    Patrice Dupont

  12. Department of Surgery, Division of Critical Care, McGill University Health Centre, Montreal, Canada

    Gordan Samoukovic

  13. Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada

    David R. Williamson

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  1. Marc-Alexandre Duceppe
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Correspondence to Marc-Alexandre Duceppe.

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Authors’ contributions

Marc-Alexandre Duceppe (ORCID: 0000-0001-5211-2600): This author had the idea for the article, helped in the research design, created and performed the search strategy, screened for citations, prepiloted the case report forms, evaluated selected citations, and participated in the writing and revision of the manuscript. Salmaan Kanji (ORCID: 0000-0003-0594-0360): This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Anh Thu Do: This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Ni Ruo: This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Yiorgos Alexandros Cavayas (ORCID: 0000-0001-7664-2104): This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Martin Albert (ORCID: 0000-0001-8364-4335): This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Maxime Robert-Halabi (ORCID: 0000-0002-3813-0965): This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Samara Zavalkoff (ORCID: 0000-0002-4447-1977): This author helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. Patrice Dupont (ORCID: 0000-0003-3634-6858): This author helped in the research design, assisted with the creation and launch of the search strategy, and participated in the writing and revision of the manuscript. Gordan Samoukovic (ORCID: 0000-0002-9169-2158): This author had the idea for the article, helped in the research design, evaluated selected citations, and participated in the writing and revision of the manuscript. David Williamson (ORCID: 0000-0003-3360-4831): This author helped in the research design, screened for citations, prepiloted the case report forms, evaluated selected citations, and participated in the writing and revision of the manuscript.

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Duceppe, MA., Kanji, S., Do, A.T. et al. Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Adults During Extracorporeal Membrane Oxygenation: A Systematic Review. Drugs 81, 1307–1329 (2021). https://doi.org/10.1007/s40265-021-01557-3

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