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Online ISSN 1827-1596
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.