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Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Pediatric Patients 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 exist for antimicrobial dosing adjustments in patients requiring extracorporeal membrane oxygenation (ECMO) therapy, particularly in the pediatric population. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill neonates and children requiring ECMO therapy.

Methods

Medline, EMBASE, Global Health and All EBM Reviews databases were queried. Grey literature was examined. All clinical studies reporting PK/PD parameters of antimicrobials in critically ill pediatric patients treated with ECMO were included, except for case reports and congress abstracts. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently extract data and evaluate the methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK reporting guidelines. Patient and study characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Broad dosing recommendations were formulated based on the available data for specific antimicrobials.

Results

Twenty-nine clinical studies were included; most were observational and uncontrolled. Patient characteristics and co-treatments were often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the drugs and population studied. It was only possible to formulate dosing recommendations for a few antimicrobials given the paucity of data, its overall low quality and heterogeneity in reporting.

Conclusion

Limited data exists on the PK/PD of antimicrobials during ECMO therapy in the pediatric population. Rigorously designed population PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring this therapeutic modality. The use of therapeutic drug monitoring for antimicrobials in pediatric patients on ECMO should be encouraged to optimize dosing.

Trial Registry

PROSPERO registration number: CRD42018099992 (Registered: July 24th 2018).

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Acknowledgements

We thank M. Patrice Dupont, librarian at the Université de Montréal, for his expertise and help with the literature search strategies.

Author information

Authors and Affiliations

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

    Marc-Alexandre Duceppe, Anh Thu Do & Ni Ruo

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

    Salmaan Kanji

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

    Salmaan Kanji

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

    Salmaan Kanji & David R. Williamson

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

    Yiorgos Alexandros Cavayas & Martin Albert

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

    Yiorgos Alexandros Cavayas & Martin Albert

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

    Yiorgos Alexandros Cavayas & Martin Albert

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

    Maxime Robert-Halabi

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

    Samara Zavalkoff

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

    Samara Zavalkoff & Gordan Samoukovic

  11. Faculté de Pharmacie, Université Paris Descartes, Paris, France

    Laura Benichou

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

    Gordan Samoukovic

  13. Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, Montreal, QC, 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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Marc-Alexandre Duceppe: No conflict of interest to declare. Salmaan Kanji: No conflict of interest to declare. Anh Thu Do: No conflict of interest to declare. Ni Ruo: No conflict of interest to declare. Yiorgos Alexandros Cavayas: No conflict of interest to declare. Martin Albert: No conflict of interest to declare. Maxime Robert-Halabi: No conflict of interest to declare. Samara Zavalkoff: No conflict of interest to declare. Laura Benichou: No conflict of interest to declare. Gordan Samoukovic: No conflict of interest to declare. David Williamson: No conflict of interest to declare.

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MAD: This author had the idea for the article, led 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. SK: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. ATD: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. NR: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. YAC: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. MA: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. MRH: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. SZ: This author helped in the research design, evaluated selected citations and participated in the writing and revision of the manuscript. LB: This author screened for citations, evaluated selected citations and participated in the writing and revision of the manuscript. GS: 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. DW: 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 Pediatric Patients During Extracorporeal Membrane Oxygenation: A Systematic Review. Pediatr Drugs 25, 515–535 (2023). https://doi.org/10.1007/s40272-023-00582-x

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