Gordan Samoukovic1,2, David R Williamson3,4, Marc-Alexandre Duceppe5, Salmaan Kanji6,7,3, Anh Thu Do8, Ni Ruo8, Yiorgos Alexandros Cavayas9,10,11, Martin Albert9,10,11, Maxime Robert-Halabi12, Samara Zavalkoff13,1, Patrice Dupont14. 1. Faculty of Medicine, McGill University, Montreal, Canada. 2. Department of Surgery, Division of Critical Care, McGill University Health Centre, Montreal, Canada. 3. Faculté de Pharmacie, Université de Montréal, Montreal, Canada. 4. Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada. 5. Department of Pharmacy, McGill University Health Centre, 1001 Boul. Décarie, Local C-RC 6004, Montreal, QC, H4A 3J1, Canada. duceppe.marc.alexandre@gmail.com. 6. Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada. 7. Faculty of Medicine, University of Ottawa, Ottawa, Canada. 8. Department of Pharmacy, McGill University Health Centre, 1001 Boul. Décarie, Local C-RC 6004, Montreal, QC, H4A 3J1, Canada. 9. Department of Medicine, Division of Critical Care, Hôpital du Sacré-Coeur de Montréal Research Centre, Montreal, Canada. 10. Department of Surgery, Division of Critical Care, Montreal Heart Institute, Montreal, Canada. 11. Département de Médecine, Faculté de Médecine, Université de Montréal, Montreal, Canada. 12. Department of Medicine, Division of Cardiology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada. 13. Department of Pediatrics, Division of Pediatric Critical Care, McGill University Health Centre, Montreal, Canada. 14. Bibliothèque de la santé, Université de Montréal, Montreal, Canada.
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).
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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