Sevoflurane sedation in a rat model of sepsis: systemic and neuro-inflammation

Background 
Volatile anesthetics such as sevoflurane have shown anti-inflammatory properties in various organs and settings [1]. We were interested in evaluating the safety profile and the potential of sevoflurane to reduce neuro- inflammation in sepsis. 

Methods 
Adult male Wistar rats (329±21g) were subjected to intravenous injection of 1mg/kg lipopolysaccharides (LPS) or sham procedure (phosphate-buffered saline, PBS) and randomly assigned to sedation with propofol or sevoflurane for 12h. Blood samples were taken every 3 hours. The inflammatory mediators cytokine-induced neutrophil chemoattractant protein-1 (CINC-1) and monocyte chemotactic protein-1 (MCP-1) were evaluated in serum and brain tissue. Brain damage marker mRNA s100B, transforming growth factor β (TGF-β) and glial fibrillary acidic protein (GFAP) as well as wet-to-dry ratio were assessed. Statistical analysis was performed using one way analysis of variance, p<0.05 was considered significant. 

Results 
There was no difference with regard to ventilation or mean arterial blood pressure in the two sedation groups. Pro-inflammatory cytokines in serum were upregulated with two peaks at 3h and at 12h in the propofol and sevoflurane sepsis group (12h CINC- 1: 401±305 vs 96±44ng/ml; 12h MCP-1 4.82±1.92 vs. 2.51±0.54μg/ml; both p<0.001), values were higher in the propofol compared to the sevoflurane group. (Fig. 1A and Fig. 1D) 
Also in brain tissue CINC-1 and MCP-1 protein was increased upon LPS injection, however, with similar values in both sedation groups. (Fig. 1C and Fig. 1F) 
Brain damage marker mRNA s100B, TGF-β and GFAP were decreased by 2%, by 25% and increased by 43% by sevoflurane, but without reaching statistical significance (p= 0.99, 0.35 and 0.42, Fig. 2B-D). 
Wet to dry ratio was not affected by the sedative regimen in septic animals (4.89±0.07 vs. 4.80±0.07, p=0.23, Fig. 2A). 

Conclusion 
Sevoflurane seems to be safe in a rat sepsis model with regard to neuro-inflammation and offering the benefit of attenuating the systemic inflammatory reaction. 

References 
[1] Lee YM et al: Biomed Res Int. 2015