Feasibility study of cytokine removal by hemoadsorption in brain-dead humans.
BACKGROUND
Inflammatory cytokines occur in the circulation and in the tissues after brain death and have been associated with dysfunction of donor organs before and after transplantation.


OBJECTIVE
To determine the feasibility of removing cytokines using a hemoadsorption device.


METHODS
Two-center, randomized, open-label, feasibility study in which brain-dead subjects were randomized to two treatment groups.


METHODS
Two U.S. academic hospitals.


METHODS
Eight brain-dead subjects deemed unsuitable for organ donation by respective organ procurement organizations.


METHODS
After obtaining consent from families, subjects were treated with hemoadsorption for 4 hrs using CytoSorb. Effects on cytokines (tumor necrosis factor, interleukin [IL]-6, and IL-10) were assessed both across the device and in the plasma over time. Feasibility for cytokine removal was assessed using objective criteria.


RESULTS
Cytokine removal across the CytoSorb device ranged from 4% to 30% and was not significantly different from 1 hr to 4 hrs. Overall removal was greatest for IL-6, 28% (p = .006), and least for tumor necrosis factor, 8.5% (p = .13). Plasma concentrations of both IL-6 and tumor necrosis factor, but not IL-10, were significantly reduced after the first hour of therapy; mean differences were -13% +/- 7% for IL-6 (p = .039), -23% +/- 9% for tumor necrosis factor (p = .02), and -2% +/- 7% of IL-10 (p = 23). However, plasma concentrations for all three cytokines increased over time and were above baseline by the end of the intervention. No adverse effects of therapy were observed. However, removal of cortisol and triiodothyronine was similar to removal of cytokines.


CONCLUSIONS
Hemoadsorption for removal of cytokines in brain-dead subjects is feasible. Evaluation of possible clinical benefit will require controlled trials in actual donors. However, the significant capacity for cytokine removal and absence of adverse events suggest that such trials are warranted.
Kellum
John A
JA
CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. kellumja@ccm.upmc.edu
Venkataraman
Ramesh
R
Powner
David
D
Elder
Michele
M
Hergenroeder
Georgene
G
Carter
Melinda
M
D000327:Adsorption; D000368:Aged; D001926:Brain Death / Q000097:blood* / Q000276:immunology; D016207:Cytokines / Q000493:pharmacokinetics*; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010865:Pilot Projects; D020858:Tissue and Organ Harvesting / Q000379:methods; D014284:Triiodothyronine / Q000097:blood
D016207:Cytokines; D014284:Triiodothyronine; D006854:Hydrocortisone