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Minerva Anestesiologica 2014 June;80(6):655-65


language: English

A pharmacokinetic study of 48-hour sevoflurane inhalation using a disposable delivery system (AnaConDa®) in ICU patients

Perbet S. 1, 2, Bourdeaux D. 3, 4, Sautou V. 3, 4, Pereira B. 5, Chabanne R. 6, Constantin J. M. 1, 2, Chopineau J. 3, 4, Bazin J. E. 1

1 CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, CHU Estaing, Clermont-Ferrand, France; 2 Université d’Auvergne, D2R2, EA-7281, Faculty of Medicine, Clermont-Ferrand, France; 3 CHU Clermont-Ferrand, Department of Pharmacy, Gabriel-Montpied Hospital, Clermont-Ferrand, France; 4 Université d’Auvergne, Faculty of Pharmacy, Laboratory of Clinical Pharmacy and Biotechnics, Clermont-Ferrand, France; 5 CHU Clermont-Ferrand, Biostatistics Unit, DRCI, Gabriel-Montpied Hospital, Clermont-Ferrand, France; 6 CHU Clermont-Ferrand, Neuro-Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, CHU Gabriel-Montpied, Clermont-Ferrand, France


BACKGROUND: Little is known regarding sevoflurane kinetics and toxicity during long-term sedation of intensive care unit (ICU) patients using the AnaConDa® system. The objective of the present study was to establish a pharmacokinetic description of 48-h sevoflurane administration, and to estimate plasma concentrations of metabolites.
METHODS: Forty-eight hour sedation with sevoflurane vaporized via an AnaConDa® device, with an end-tidal concentration objective of 1.5% (v/v), was initiated in 12 non-obese patients who did not have hepatic or renal failure but who required sedation for more than 48 h in our ICU. Plasma sevoflurane, hexafluoroisopropanol, and fluoride concentrations were determined over this time period and pharmacokinetic analysis was performed.
RESULTS: The mean plasma concentration of sevoflurane was 76 mg/L at 24 h and 70 mg/L at 48 h. Wash-out of plasma sevoflurane correlated with a rapid decrease in the mean end-tidal sevoflurane level. The mean free plasma fraction of hexafluoroisopropanol never exceeded 8 mg/mL. The mean fluoride concentration was 0.8 µmol/L on day 0, 51.7 µmol/L on day 1, and 68.1 µmol/L on day 2 (P<0.0001). The distribution volume was 53 L, the elimination constant 2.9 h-1, the transfer constant from compartment 1 to compartment 2 (K1-2) 1.2 h-1, the K2-1 0.26 h-1, the half-life of elimination 3.78 h, and the total clearance 156 L/h.
CONCLUSION: Following 48 hours of sedation using sevoflurane inhalation administered using an AnaConDa® delivery device, sevoflurane washout was rapid. Plasma fluoride levels accumulated over the study period without apparent nephrotoxicity.

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