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Extracorporeal Membrane Oxygenation Can Affect Posaconazole Exposure in Critically Ill Patients
Ming G Chai1,2, Rekha P Mangalore3,4, Joshua F Ihle2,5
1Pharmacy Department, Alfred Health, Melbourne, Victoria, Australia.
Background:
Posaconazole is an antifungal agent used to prevent or treat invasive fungal infections (IFIs) in critically ill patients, including those receiving extracorporeal membrane oxygenation (ECMO). However, in vitro data suggest that posaconazole is extensively sequestered in ECMO circuits. The aim of this study was to determine the impact of ECMO on posaconazole concentrations in critically ill patients.
Methods:
The authors conducted a retrospective cohort study involving patients receiving intravenous posaconazole in the intensive care unit from January 2014 to July 2024. Posaconazole concentrations at the first sampling and the proportion of patients achieving target concentrations for prophylaxis (>0.7 mg/L) and treatment (>1 mg/L) of IFI were assessed. Patients receiving ECMO were compared with non-ECMO patients. In addition, the impact of ECMO initiation or decannulation on posaconazole concentrations was examined.
Results:
In total, 19 patients (8 ECMO and 11 non-ECMO) were included. ECMO patients had lower posaconazole concentrations (median [interquartile range], 0.7 [0.5-0.7] mg/L versus 1.2 [0.7-1.4] mg/L, P = 0.04) and were less likely to reach therapeutic concentrations (13% versus 64%, P = 0.04). Fewer ECMO patients achieved concentrations required for prophylaxis, although this difference was not statistically significant (50% versus 82%, P = 0.17). ECMO initiation was associated with a reduction in posaconazole concentration (n = 1), whereas decannulation was associated with an increase (n = 3).
Conclusions:
ECMO patients may be at an increased risk of subtherapeutic posaconazole concentrations for treating IFI, and ECMO decannulation may increase concentrations. Close therapeutic drug monitoring is recommended, especially during ECMO initiation and decannulation, to ensure posaconazole concentrations are appropriate for treating or preventing IFI.
Insights
Extracorporeal membrane oxygenation (ECMO) significantly reduces posaconazole levels in critically ill patients, increasing the risk of subtherapeutic antifungal concentrations. Therapeutic drug monitoring is crucial, especially during ECMO initiation and decannulation.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Posaconazole is vital for preventing and treating invasive fungal infections (IFIs) in critically ill patients.
- Extracorporeal membrane oxygenation (ECMO) circuits may sequester posaconazole, potentially reducing its efficacy.
- Understanding ECMO's impact on posaconazole levels is crucial for patient management.
Purpose of the Study:
- To evaluate the effect of ECMO on posaconazole concentrations in critically ill patients.
- To compare posaconazole levels and target attainment between ECMO and non-ECMO patients.
- To assess changes in posaconazole concentrations during ECMO initiation and decannulation.
Main Methods:
- Retrospective cohort study of critically ill patients receiving intravenous posaconazole.
- Comparison of posaconazole concentrations and achievement of target levels (>0.7 mg/L for prophylaxis, >1 mg/L for treatment) between ECMO and non-ECMO groups.
- Analysis of posaconazole concentration changes related to ECMO initiation and decannulation.
Main Results:
- ECMO patients exhibited significantly lower posaconazole concentrations (0.7 mg/L vs. 1.2 mg/L) compared to non-ECMO patients.
- A lower proportion of ECMO patients achieved therapeutic posaconazole concentrations (13% vs. 64%).
- ECMO initiation was linked to decreased posaconazole levels, while decannulation was associated with increased levels.
Conclusions:
- Critically ill patients on ECMO are at higher risk of subtherapeutic posaconazole concentrations, potentially compromising IFI treatment.
- ECMO decannulation may lead to increased posaconazole concentrations.
- Intensive therapeutic drug monitoring of posaconazole is essential in ECMO patients, particularly around ECMO initiation and decannulation.
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