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

Crit Care Med. 2008 May;36(5):1573-7. doi: 10.1097/CCM.0b013e318170b9a7.

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)-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytokines* / blood
  • Hemadsorption*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / blood
  • Sepsis / mortality*
  • Sepsis / therapy*
  • Survival Rate
  • Time Factors

Substances

  • Cytokines