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


CONCLUSIONS
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.
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, CHU Estaing, Clermont-Ferrand, France - sperbet@chu-clermontferrand.fr.
S
S
Perbet
D
D
Bourdeaux
V
V
Sautou
B
B
Pereira
R
R
Chabanne
J M
JM
Constantin
J
J
Chopineau
J E
JE
Bazin
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000776:Anesthesiology / Q000295:instrumentation*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004209:Disposable Equipment; D005260:Female; D006207:Half-Life; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane