Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

doi:10.1007/s40262-023-01264-0

Review

. 2023 Jul;62(7):931-942.

doi: 10.1007/s40262-023-01264-0. Epub 2023 Jun 10.

Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

Haifa Lyster^{1

2}, Kiran Shekar^{3

4

5

6}, Kevin Watt^{7

8}, Anna Reed^{1

9}, Jason A Roberts^{10

11

12

13

14}, Mohd-Hafiz Abdul-Aziz¹⁵

Affiliations

¹ Royal Brompton and Harefield Hospitals, Part of Guy's and St Thomas' NHS Foundation Trust, London, UK.
² University of Portsmouth, Portsmouth, UK.
³ Adult Intensive Care Services and Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.
⁴ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁵ Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
⁶ Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia.
⁷ School of Pharmacy, University of Waterloo, 10 Victoria St S. Kitchener, Waterloo, ON, N2G 1C5, Canada.
⁸ Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁹ Imperial College London, London, SW3 6NP, UK.
¹⁰ Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia. j.roberts2@uq.edu.au.
¹¹ Herston Infectious Diseases (HeIDI), Metro North Health, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
¹² Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia. j.roberts2@uq.edu.au.
¹³ Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. j.roberts2@uq.edu.au.
¹⁴ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France. j.roberts2@uq.edu.au.
¹⁵ Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

PMID: 37300631
PMCID: PMC10338597
DOI: 10.1007/s40262-023-01264-0

Review

Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

Haifa Lyster et al. Clin Pharmacokinet. 2023 Jul.

. 2023 Jul;62(7):931-942.

doi: 10.1007/s40262-023-01264-0. Epub 2023 Jun 10.

Authors

Haifa Lyster^{1

2}, Kiran Shekar^{3

4

5

6}, Kevin Watt^{7

8}, Anna Reed^{1

9}, Jason A Roberts^{10

11

12

13

14}, Mohd-Hafiz Abdul-Aziz¹⁵

Affiliations

¹ Royal Brompton and Harefield Hospitals, Part of Guy's and St Thomas' NHS Foundation Trust, London, UK.
² University of Portsmouth, Portsmouth, UK.
³ Adult Intensive Care Services and Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.
⁴ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁵ Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
⁶ Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia.
⁷ School of Pharmacy, University of Waterloo, 10 Victoria St S. Kitchener, Waterloo, ON, N2G 1C5, Canada.
⁸ Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁹ Imperial College London, London, SW3 6NP, UK.
¹⁰ Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia. j.roberts2@uq.edu.au.
¹¹ Herston Infectious Diseases (HeIDI), Metro North Health, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
¹² Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia. j.roberts2@uq.edu.au.
¹³ Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. j.roberts2@uq.edu.au.
¹⁴ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France. j.roberts2@uq.edu.au.
¹⁵ Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

PMID: 37300631
PMCID: PMC10338597
DOI: 10.1007/s40262-023-01264-0

Abstract

Extracorporeal membrane oxygenation (ECMO) is an established advanced life support system, providing temporary cardiac and/or respiratory support in critically ill patients. Fungal infections are associated with increased mortality in patients on ECMO. Antifungal drug dosing for critically ill patients is highly challenging because of altered pharmacokinetics (PK). PK changes during critical illness; in particular, the drug volume of distribution (V_d) and clearance can be exacerbated by ECMO. This article discusses the available literature to inform adequate dosing of antifungals in this patient population. The number of antifungal PK studies in critically ill patients on ECMO is growing; currently available literature consists of case reports and studies with small sample sizes providing inconsistent findings, with scant or no data for some antifungals. Current data are insufficient to provide definitive empirical drug dosing guidance and use of dosing strategies derived from critically patients not on ECMO is reasonable. However, due to high PK variability, therapeutic drug monitoring should be considered where available in critically ill patients receiving ECMO to prevent subtherapeutic or toxic antifungal exposures.

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Conflict of interest statement

There are no conflicts of interest known for this manuscript.

Figures

**Fig. 1**
Pharmacokinetic changes in critically ill patients receiving ECMO and alternative dosing strategies

See this image and copyright information in PMC

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References

1. Bartlett RH. Extracorporeal life support: history and new directions. ASAIO J. 2005;51(5):487–489. doi: 10.1097/01.mat.0000179141.08834.cb. - DOI - PubMed
1. Bartlett RH, Gattinoni L. Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76(7):534–540. - PubMed
1. Zangrillo A, Landoni G, Biondi-Zoccai G, Greco M, Greco T, Frati G, et al. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc. 2013;15(3):172–178. - PubMed
1. Bizzarro MJ, Conrad SA, Kaufman DA, Rycus P. Infections acquired during extracorporeal membrane oxygenation in neonates, children, and adults. Pediatr Crit Care Med. 2011;12(3):277–281. doi: 10.1097/PCC.0b013e3181e28894. - DOI - PubMed
1. Vogel AM, Lew DF, Kao LS, Lally KP. Defining risk for infectious complications on extracorporeal life support. J Pediatr Surg. 2011;46(12):2260–2264. doi: 10.1016/j.jpedsurg.2011.09.013. - DOI - PubMed

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[1] Bartlett RH. Extracorporeal life support: history and new directions. ASAIO J. 2005;51(5):487–489. doi: 10.1097/01.mat.0000179141.08834.cb. - DOI - PubMed

[2] Bartlett RH. Extracorporeal life support: history and new directions. ASAIO J. 2005;51(5):487–489. doi: 10.1097/01.mat.0000179141.08834.cb. - DOI - PubMed

[3] Bartlett RH, Gattinoni L. Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76(7):534–540. - PubMed

[4] Bartlett RH, Gattinoni L. Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76(7):534–540. - PubMed

[5] Zangrillo A, Landoni G, Biondi-Zoccai G, Greco M, Greco T, Frati G, et al. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc. 2013;15(3):172–178. - PubMed

[6] Zangrillo A, Landoni G, Biondi-Zoccai G, Greco M, Greco T, Frati G, et al. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc. 2013;15(3):172–178. - PubMed

[7] Bizzarro MJ, Conrad SA, Kaufman DA, Rycus P. Infections acquired during extracorporeal membrane oxygenation in neonates, children, and adults. Pediatr Crit Care Med. 2011;12(3):277–281. doi: 10.1097/PCC.0b013e3181e28894. - DOI - PubMed

[8] Bizzarro MJ, Conrad SA, Kaufman DA, Rycus P. Infections acquired during extracorporeal membrane oxygenation in neonates, children, and adults. Pediatr Crit Care Med. 2011;12(3):277–281. doi: 10.1097/PCC.0b013e3181e28894. - DOI - PubMed

[9] Vogel AM, Lew DF, Kao LS, Lally KP. Defining risk for infectious complications on extracorporeal life support. J Pediatr Surg. 2011;46(12):2260–2264. doi: 10.1016/j.jpedsurg.2011.09.013. - DOI - PubMed

[10] Vogel AM, Lew DF, Kao LS, Lally KP. Defining risk for infectious complications on extracorporeal life support. J Pediatr Surg. 2011;46(12):2260–2264. doi: 10.1016/j.jpedsurg.2011.09.013. - DOI - PubMed

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Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

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Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

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