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Open Access Research

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

Jens Altrichter1, Martin Sauer2, Katharina Kaftan1, Thomas Birken2, Doris Gloger3, Martin Gloger4, Jörg Henschel4, Heiko Hickstein1, Ernst Klar5, Sebastian Koball1, Annette Pertschy5, Gabriele Nöldge-Schomburg2, Dierk A Vagts2 and Steffen R Mitzner1*

Author Affiliations

1 Department of Medicine, Division of Nephrology, Medical Faculty of the University of Rostock, Ernst-Heydemann-Str. 6, Rostock, D-18057, Germany

2 Department of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, Schillingallee 35, Rostock, D-18057, Germany

3 Department of Medicine, Division of Transfusion Medicine, Medical Faculty of the University of Rostock, Ernst-Heydemann-Str. 6, Rostock, D-18057, Germany

4 Department of Medicine, Intensive Care Unit, Medical Faculty of the University of Rostock, Ernst-Heydemann-Str. 6, Rostock, D-18057, Germany

5 Department of Surgery, Medical Faculty of the University of Rostock, Schillingallee 35, Rostock, D-18057, Germany

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Critical Care 2011, 15:R82  doi:10.1186/cc10076

Published: 3 March 2011

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