Impact of lung imaging phenotypes on sevoflurane pharmacokinetics and pharmacodynamics during inhaled sedation in patients with acute respiratory distress syndrome: a case-control study. Interim analysis

Background: lung morphology (focal and nonfocal) of injury during acute respiratory distress syndrome (ARDS) has a major impact on outcomes and reflects the severity of lung injury. Sevoflurane is safe and associated with improved oxygenation, reduced levels of some pro-inflammatory markers and reduced lung epithelial injury. Data suggest differential responses to sevoflurane in focal and nonfocal ARDS phenotypes, but the mechanism remains unknown. The aim of this study is to compare the pharmacokinetic of sevoflurane-induced sedation during ARDS depending on the lung morphology.Methods: the SPIDERMAN study is a case control study in six ICU. Two groups of patients with moderate-to-severe ARDS will be enrolled, depending on their lung morphotype (focal or nonfocal). These patients will receive inhaled sevoflurane as a standard practice of sedation. The primary endpoint is the determination of plasma concentrations of sevoflurane in patients with focal and those with nonfocal ARDS. Plasma concentrations of sevoflurane will be measured in both study groups from the start of sedation up to 48h at specific time-points and immediately after cessation of sevoflurane up to 6h. The secondary endpoints include the report of plasma concentration of hexafluoroisopropanol, the fraction of inspired and expired sevoflurane, the infusion rates of sevoflurane, the infusion rates of remifentanil, the bispectral index values, the evolution of renal function and PaO2 / FIO2 ratios between patients with focal and nonfocal ARDS. 40 patients will be recruited.Results: a total of 20 patients have been included in the study for the interim analysis. The plasma concentrations of sevoflurane and HFIP were not different between two groups. No significant differences were observed between the focal and nonfocal ARDS groups for the sevoflurane administration features, bispectral index, PaO2 / FIO2. no impact on renal function.Conclusion: in interim analysis no significant difference in the pharmacokinetics of sevoflurane in the nonfocal compared to focal ARDS patients