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Critical Care
Published in: Critical Care 2/2011

Open Access 01-04-2011 | Research

Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study

Authors: Jens Altrichter, Martin Sauer, Katharina Kaftan, Thomas Birken, Doris Gloger, Martin Gloger, Jörg Henschel, Heiko Hickstein, Ernst Klar, Sebastian Koball, Annette Pertschy, Gabriele Nöldge-Schomburg, Dierk A Vagts, Steffen R Mitzner

Published in: Critical Care | Issue 2/2011

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Abstract

Introduction

Neutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials.

Methods

The trial was conducted as a prospective uncontrolled clinical phase I/II study with 28-day follow-up at three university hospital intensive care units. Ten consecutive patients (five men, five women, mean age 60.3 ± 13.9 standard deviation (SD) years) with septic shock with mean ICU entrance scores of Acute Physiology and Chronic Health Evaluation (APACHE) II of 29.9 ± 7.2 and of Simplified Acute Physiology Score (SAPS) II of 66.2 ± 19.5 were treated twice within 72 hours for a mean of 342 ± 64 minutes/treatment with an extracorporeal bioreactor containing 1.41 ± 0.43 × 10E10 granulocytes from healthy donors. On average, 9.8 ± 2.3 liters separated plasma were treated by the therapeutic donor cells. Patients were followed up for 28 days.

Results

Tolerance and technical safety during treatment, single organ functions pre/post treatment, and hospital survival were monitored. The extracorporeal treatments were well tolerated. During the treatments, the bacterial endotoxin concentration showed significant reduction. Furthermore, noradrenaline dosage could be significantly reduced while mean arterial pressure was stable. Also, C-reactive protein, procalcitonin, and human leukocyte antigen DR (HLA-DR) showed significant improvement. Four patients died in the hospital on days 6, 9, 18 and 40. Six patients could be discharged.

Conclusions

The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.

Trial registration

ClinicalTrials.gov Identifier: NCT00818597
Appendix
Available only for authorised users
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Metadata
Title
Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study
Authors
Jens Altrichter
Martin Sauer
Katharina Kaftan
Thomas Birken
Doris Gloger
Martin Gloger
Jörg Henschel
Heiko Hickstein
Ernst Klar
Sebastian Koball
Annette Pertschy
Gabriele Nöldge-Schomburg
Dierk A Vagts
Steffen R Mitzner
Publication date
01-04-2011
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2011
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc10076

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