Effects of hemoadsorption on cytokine removal and short-term survival in septic rats


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Abstract

Objective:A broad-spectrum immune-regulating therapy could be beneficial in the treatment of sepsis. Our previous studies have shown that a hemoadsorption device (CytoSorb) removes both pro- and anti-inflammatory cytokines and improves survival in experimental endotoxemia. We sought to determine whether hemoadsorption can also be effective in the treatment of sepsis.Design:Randomized controlled laboratory experiment.Setting:University laboratory.Interventions:Rats were subjected to cecal ligation and puncture (CLP) and 20 hrs later were randomized to receive either hemoadsorption or sham treatment using an arterial-venous circuit. Hemoadsorption was accomplished using a cartridge containing Cytosorb beads. Blood was drawn for cytokine measurements and mean arterial pressure (MAP) was continuously monitored. Cytokines were measured via multiplex bead immunoassays. Survival time was observed for 9 hours after the intervention and assessed by Kaplan–Meier statistics. The overall survival in each group was compared using Fisher's exact test. Finally, we used a Cox proportional-hazards model to examine the effects of cytokine removal on survival time.Measurements and Main Results:Baseline plasma cytokine concentrations and MAP were similar between hemoadsorption and sham-treated groups. However, the concentrations of tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-10 were significantly lower after hemoadsorption compared to the sham group. Six hours after treatment ended, IL-6 and IL-10 concentrations were still lower in hemoadsorption group. MAP was significantly better in hemoadsorption compared to sham-treated animals (p < .05). Finally, mean survival time was significantly longer (720 vs. 381 min, p < .05, Mann–Whitney test), and overall survival was significantly better (11/17 vs. 2/16, p < .01) with hemoadsorption compared to sham. Combined reduction in both IL-6 and IL-10 was associated with a significantly decreased risk of death (hazard ratio, .11, p = .005).Conclusion:Hemoadsorption reduced circulating cytokines, improved MAP, and resulted in better short-term survival in CLP-induced septic rats.

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