• Sebastien Perbet, Daniel Bourdeaux, Alexandre Lenoire, Claire Biboulet, Bruno Pereira, Malha Sadoune, Benoit Plaud, Jean-Marie Launay, Jean-Etienne Bazin, Valerie Sautou, Alexandre Mebazaa, Pascal Houze, Jean-Michel Constantin, Matthieu Legrand, and PRONOBURN group.
• Intensive Care Unit, Department of Perioperative Medicine, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France; Inserm U1103, GReD, CNRS 6293, université Clermont-Auvergne, 63000 Clermont-Ferrand, France.
• Anaesth Crit Care Pain Med. 2018 Dec 1; 37 (6): 551-556.

BackgroundSevoflurane has anti-inflammatory proprieties and short lasting effects making it of interest for procedural sedation in critically ill patients. We evaluated the pharmacokinetics of sevoflurane and metabolites in severely ill burn patients and controls. The secondary objective was to assess potential kidney injury.MethodsProspective interventional study in a burn and a surgical intensive care unit; 24 mechanically ventilated critically ill patients (12 burns, 12 controls) were included. The sevoflurane was administered with an expired fraction target of 2% during short-term procedural sedation. Plasma concentrations of sevoflurane, hexafluoroisopropanolol (HFIP) and free fluoride ions were recorded at different times. Kinetic Pro (Wgroupe, France) was used for pharmacokinetic analysis. Kidney injury was assessed with neutrophil gelatinase-associated lipocalin (NGAL).ResultsThe mean total burn surface area was 36±11%. The average plasma concentration of sevoflurane was 70.4±37.5mg·L-1 in burns and 57.2±28.1mg·L-1 in controls at the end of the procedure (P=0.58). The volume of distribution was higher (46.8±7.2 vs 22.2±2.50L, P<0.001), and the drug half-life longer in burns (1.19±0.28h vs 0.65±0.04h, P<0.0001). Free metabolite HFIP was higher in burns. Plasma fluoride was not different between burns and controls. NGAL did not rise after procedures.ConclusionWe observed an increased volume of distribution, slower elimination rate, and altered metabolism of sevoflurane in burn patients compared to controls. Repeated use for procedural sedation in burn patients needs further evaluation. No renal toxicity was detected.Trial Registry NumberClinicalTrials.gov Identifier NCT02048683.Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

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