严重新型冠状病毒肺炎需体外膜肺氧合治疗患者的细胞因子吸附（CYCOV）：一项单中心、开放标签、随机对照试验

Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial.

作者信息

Supady Alexander, Weber Enya, Rieder Marina, Lother Achim, Niklaus Tim, Zahn Timm, Frech Franziska, Müller Sissi, Kuhl Moritz, Benk Christoph, Maier Sven, Trummer Georg, Flügler Annabelle, Krüger Kirsten, Sekandarzad Asieb, Stachon Peter, Zotzmann Viviane, Bode Christoph, Biever Paul M, Staudacher Dawid, Wengenmayer Tobias, Graf Erika, Duerschmied Daniel

机构信息

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Germany; Heidelberg Institute of Global Health, University of Heidelberg, Germany.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Medical Center, Faculty of Medicine, University of Freiburg, Germany.

出版信息

Lancet Respir Med. 2021 Jul;9(7):755-762. doi: 10.1016/S2213-2600(21)00177-6. Epub 2021 May 14.

DOI:10.1016/S2213-2600(21)00177-6

PMID:34000236

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8121541/

Abstract

BACKGROUND

We sought to clarify the benefit of cytokine adsorption in patients with COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO).

METHODS

We did a single-centre, open-label, randomised, controlled trial to investigate cytokine adsorption in adult patients with severe COVID-19 pneumonia requiring ECMO. Patients with COVID-19 selected for ECMO at the Freiburg University Medical Center (Freiburg, Germany) were randomly assigned (1:1) to receive cytokine adsorption using the CytoSorb device or not. Randomisation was computer-generated, allocation was concealed by opaque, sequentially numbered sealed envelopes. The CytoSorb device was incorporated into the ECMO circuit before connection to the patient circuit, replaced every 24 h, and removed after 72 h. The primary endpoint was serum interleukin-6 (IL-6) concentration 72 h after initiation of ECMO analysed by intention to treat. Secondary endpoints included 30-day survival. The trial is registered with ClinicalTrials.gov (NCT04324528) and the German Clinical Trials Register (DRKS00021300) and is closed.

FINDINGS

From March 29, 2020, to Dec 29, 2020, of 34 patients assessed for eligibility, 17 (50%) were treated with cytokine adsorption and 17 (50%) without. Median IL-6 decreased from 357·0 pg/mL to 98·6 pg/mL in patients randomly assigned to cytokine adsorption and from 289·0 pg/mL to 112·0 pg/mL in the control group after 72 h. One patient in each group died before 72 h. Adjusted mean log IL-6 concentrations after 72 h were 0·30 higher in the cytokine adsorption group (95% CI -0·70 to 1·30, p=0·54). Survival after 30 days was three (18%) of 17 with cytokine adsorption and 13 (76%) of 17 without cytokine adsorption (p=0·0016).

INTERPRETATION

Early initiation of cytokine adsorption in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6 and had a negative effect on survival. Cytokine adsorption should not be used during the first days of ECMO support in COVID-19.

FUNDING

None.

摘要

背景

我们试图阐明细胞因子吸附疗法对接受静脉-静脉体外膜肺氧合（ECMO）支持的新型冠状病毒肺炎（COVID-19）患者的益处。

方法

我们进行了一项单中心、开放标签、随机对照试验，以研究细胞因子吸附疗法对需要ECMO的重症COVID-19肺炎成年患者的疗效。在德国弗莱堡大学医学中心被选定接受ECMO治疗的COVID-19患者被随机分配（1:1）接受或不接受使用CytoSorb装置的细胞因子吸附疗法。随机分组由计算机生成，分配情况通过不透明的、顺序编号的密封信封进行隐藏。CytoSorb装置在连接到患者回路之前被并入ECMO回路，每24小时更换一次，并在72小时后移除。主要终点是按意向性分析在ECMO开始后72小时的血清白细胞介素-6（IL-6）浓度。次要终点包括30天生存率。该试验已在ClinicalTrials.gov（NCT04324528）和德国临床试验注册中心（DRKS00021300）注册，现已结束。

结果

从2020年3月29日至2020年12月29日，在34名评估合格的患者中，17名（50%）接受了细胞因子吸附疗法，17名（50%）未接受。随机分配接受细胞因子吸附疗法的患者中，IL-6中位数在72小时后从357.0 pg/mL降至98.6 pg/mL，而对照组从289.0 pg/mL降至112.0 pg/mL。每组各有一名患者在72小时前死亡。72小时后，细胞因子吸附疗法组调整后的平均IL-6对数浓度高0.30（95%CI -0.70至1.30，p = 0.54）。接受细胞因子吸附疗法的17名患者中有3名（18%）在30天后存活，未接受细胞因子吸附疗法的17名患者中有13名（76%）存活（p = 0.0016）。