Medline ® Abstract for Reference 18
of 'Investigational and ineffective therapies for sepsis'
18
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Effects of hemoadsorption on cytokine removal and short-term survival in septic rats.
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Peng ZY, Carter MJ, Kellum JA
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Crit Care Med. 2008 May;36(5):1573-7.
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)-1beta, 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.
AD
The Clinical Research, Investigation, and Systems Modeling of Acute Illness Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
PMID