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Feasibility study of cytokine removal by hemoadsorption in brain-dead humans*

Kellum, John A. MD, FCCM; Venkataraman, Ramesh MD; Powner, David MD, FCCM; Elder, Michele RN; Hergenroeder, Georgene RN; Carter, Melinda BS

doi: 10.1097/01.CCM.0000291646.34815.BB
Neurologic Critical Care
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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.

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

Setting: Two U.S. academic hospitals.

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

Main Outcome Measures: 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.

From the CRISMA Laboratory (Clinical Research, Investigation, and Systems Modeling of Acute Illness), Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA (JAK, RV, ME, MC); and the Neurosurgery Department, University of Texas Health Science Center at Houston, Houston, TX (DP, GH).

The authors have not disclosed any potential conflicts of interest.

Supported, in part, by the HIDonOR (Hemoadsorption to Improve Donor Organ Recovery) grant, HRSA 1 R38OT01300-01-00, from the Health Resources and Services Administration, U.S. Department of Health and Human Services, with additional support from MedaSorb Technologies, Princeton, NJ, which provided the CytoSorb devices; Diagnostic Products Corporation, Los Angeles, CA, which provided the cytokine assays; and Arrow International, Reading, PA, which provided the dialysis catheters.

For information regarding this article, E-mail: kellumja@ccm.upmc.edu

© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins