Department of Medicine, Division of Nephrology, Medical Faculty of University of Rostock, Ernst-Heydemann-Str. 6, Rostock, D-18057, Germany.
Crit Care. 2011;15(2):R82. doi: 10.1186/cc10076. Epub 2011 Mar 3.
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.
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.
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.
The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.
ClinicalTrials.gov Identifier: NCT00818597.
中性粒细胞是细菌感染的第一道防线。然而，粒细胞也会导致严重的局部组织损伤。为了使用供体粒细胞，同时又避免局部副作用，我们开发了一种体外免疫支持系统。这项首例人体研究旨在探讨使用粒细胞生物反应器进行体外血浆治疗在脓毒性休克患者中的耐受性。另一个目的是为后续的对照试验找到合适的疗效终点。
该试验采用前瞻性非对照临床 I/II 期研究，在 3 个大学医院重症监护病房进行为期 28 天的随访。连续 10 例（男 5 例，女 5 例，平均年龄 60.3 ± 13.9 岁标准差 (SD)）脓毒性休克患者，平均 ICU 入院评分急性生理学和慢性健康评估 (APACHE) II 为 29.9 ± 7.2，简化急性生理学评分 (SAPS) II 为 66.2 ± 19.5，在 72 小时内接受两次治疗，每次治疗时间为 342 ± 64 分钟/次，使用含有 1.41 ± 0.43 × 10E10 个健康供体粒细胞的体外生物反应器进行治疗。平均每治疗 9.8 ± 2.3 升分离血浆。患者随访 28 天。
监测治疗期间的耐受性和技术安全性、治疗前后单一器官功能以及住院生存率。体外治疗耐受性良好。治疗过程中，细菌内毒素浓度显著降低。此外，去甲肾上腺素剂量可显著减少，而平均动脉压保持稳定。C 反应蛋白、降钙素原和人白细胞抗原 DR（HLA-DR）也有显著改善。4 例患者分别于第 6、9、18 和 40 天在医院死亡。6 例患者出院。
供体粒细胞的体外治疗似乎耐受性良好，并显示出有希望的疗效结果，鼓励进一步研究。
ClinicalTrials.gov 标识符：NCT00818597。
