Sevoflurane for procedural sedation in critically ill patients: A pharmacokinetic comparative study between burn and non-burn patients
Résumé
Background
Sevoflurane 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.
Methods
Prospective 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).
Results
The mean total burn surface area was 36 ± 11%. The average plasma concentration of sevoflurane was 70.4 ± 37.5 mg·L−1 in burns and 57.2 ± 28.1 mg·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 ± 2.50 L, P < 0.001), and the drug half-life longer in burns (1.19 ± 0.28 h vs 0.65 ± 0.04 h, 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.
Conclusion
We 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.