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Voriconazole Pharmacokinetics in Critically Ill Patients and Extracorporeal Membrane Oxygenation Support: A

Mar Ronda1, Josep Manuel Llop-Talaveron2,3, MariPaz Fuset4

  • 1Infectious Disease Department, Hospital Universitari de Bellvitge-IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.

Antibiotics (Basel, Switzerland)
|July 29, 2023
PubMed

Insights

Extracorporeal membrane oxygenation (ECMO) support significantly lowers voriconazole drug levels in critically ill patients. Therapeutic drug monitoring and dose adjustments are crucial for achieving effective antifungal concentrations during ECMO.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Infectious Diseases

Background:

  • Voriconazole, a key antifungal, exhibits significant pharmacokinetic variability.
  • Achieving target minimum plasma concentrations (Cmin) of 1-5.5 mg/L is vital for voriconazole efficacy.
  • Fungal infections are common in patients on extracorporeal membrane oxygenation (ECMO), but voriconazole pharmacokinetics during ECMO are poorly understood.

Purpose of the Study:

  • To compare voriconazole pharmacokinetics in critically ill patients with and without ECMO support.
  • To identify factors influencing voriconazole Cmin in patients receiving ECMO.

Main Methods:

  • Retrospective cohort study comparing voriconazole Cmin in non-ECMO and ECMO groups.
  • Analysis of 26 Cmin determinations in 15 non-ECMO patients and 27 Cmin determinations in 9 ECMO patients.
  • Multivariate analysis to identify risk factors for low Cmin.

Main Results:

  • The ECMO group exhibited significantly lower voriconazole Cmin (0.38 ± 2.98 mg/L) compared to the non-ECMO group (3.62 ± 3.88 mg/L).
  • A higher proportion of infratherapeutic Cmin values were observed in the ECMO group (16 vs. 1).
  • ECMO support and lower plasma albumin levels were identified as independent risk factors for subtherapeutic voriconazole Cmin.

Conclusions:

  • ECMO support is associated with significantly reduced voriconazole Cmin.
  • Therapeutic drug monitoring and dose optimization are essential for voriconazole therapy in ECMO patients.
  • Higher voriconazole doses (6.44 mg/kg BID) may be required to achieve therapeutic Cmin in ECMO patients.
Keywords:
extracorporeal membrane oxygenationtherapeutic drug monitoringvoriconazole

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