Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia*
- 1 March 2004
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 32 (3), 801-805
- https://doi.org/10.1097/01.ccm.0000114997.39857.69
Abstract
Previous studies have shown that inflammatory mediators can be removed from the circulation with hemofiltration and that adsorption plays an important role. Because adsorptive capacity of hollow-fiber dialyzers is limited, we sought to determine whether hemoadsorption using high surface area beads would result in greater mediator removal and improved survival in experimental sepsis. Randomized controlled laboratory experiment. University laboratory. Sixty-six adult Sprague-Dawley rats. We conducted two ex vivo and two in vivo experiments. For in vivo experiments, we administered Escherichia coli endotoxin (20 mg/kg) by intravenous infusion and then randomized each animal to receive either hemoadsorption or a sham circuit for 4 hrs. Hemoadsorption was performed for 4 hrs using an arterial-venous circuit and a CytoSorb cartridge containing 10 g of polystyrene divinyl benzene copolymer beads with a biocompatible polyvinylpyrrolidone coating. Survival time was measured to a maximum of 12 hrs. In a separate set of experiments, we studied 12 animals using the same protocol except that we killed all animals at 4 hrs and removed standardized sections of liver for analysis of nuclear factor-kappaB DNA binding. Mean survival time among hemoadsorption-treated animals was 629+/-114 vs. 518+/-120 mins for sham-treated animals (p <.01). Overall survival (defined at 12 hrs) was also significantly better in the hemoadsorption group, seven of 20 vs. one of 20 (p <.05). Plasma interleukin-6 and interleukin-10 concentrations and liver nuclear factor-kappaB DNA binding were significantly reduced by hemoadsorption. Ex vivo experiments showed no endotoxin adsorption but strengthened our in vivo observations by showing rapid adsorption of tumor necrosis factor, interleukin-6, and interleukin-10. Hemoadsorption was associated with reduced inflammation and improved survival in this murine model of septic shock.Keywords
This publication has 18 references indexed in Scilit:
- Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic ShockJama-Journal Of The American Medical Association, 2002
- Effect of hemofiltration filter adsorption on circulating IL-6 levels in septic ratsCritical Care, 2002
- Efficacy and Safety of Recombinant Human Activated Protein C for Severe SepsisThe New England Journal of Medicine, 2001
- Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shockCritical Care Medicine, 2000
- The Effect of Intensive Plasma Water Exchange by Hemofiltration on Hemodynamics and Soluble Mediators in Canine EndotoxemiaAmerican Journal of Respiratory and Critical Care Medicine, 2000
- Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass graftingJournal of Cardiothoracic and Vascular Anesthesia, 1999
- Diffusive vs. convective therapyCritical Care Medicine, 1998
- The sirens' songs of confirmatory sepsis trialsCritical Care Medicine, 1998
- Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swineCritical Care Medicine, 1993
- Detection of Circulating Tumor Necrosis Factor after Endotoxin AdministrationThe New England Journal of Medicine, 1988