OBJECTIVES: 

To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19–associated vasoplegic shock.

DESIGN: 

Prospective, randomized controlled pilot study.

SETTING: 

Eight ICUs at three sites of the tertiary-care university hospital Charité—Universitätsmedizin Berlin.

PATIENTS: 

COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis.

INTERVENTIONS: 

Randomization of 1:1 to receive CytoSorb for 3–7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change.

MEASUREMENTS AND MAIN RESULTS: 

The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4–5 d) and 4 days (IQR, 3–5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54–2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61–2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups.

CONCLUSIONS: 

In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.

中文翻译：

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CytoSorb 拯救患有血管麻痹性休克和多器官衰竭的 COVID-19 患者：一项前瞻性、开放标签、随机对照试点研究*

目标： 

旨在研究 CytoSorb（CytoSorbents，Monmouth Junction，新泽西州）减少体外细胞因子对 COVID-19 相关血管麻痹性休克的影响。

设计： 

前瞻性、随机对照试点研究。

环境： 

柏林夏里特大学医院三个地点设有八个 ICU。

患者： 

患有血管麻痹性休克的COVID-19 患者，需要去甲肾上腺素大于 0.2 µg/kg/min，C 反应蛋白大于 100 mg/L，并有血液透析指征。

干预措施： 

按 1:1 随机分配接受 CytoSorb 3-7 天或标准治疗。为了解决无意中去除抗生素的问题，治疗组的患者在每次更换吸附剂时接受了额外的剂量。

测量和主要结果： 

主要终点是血管麻痹性休克消退的时间，通过 Cox 回归估计。次要终点包括死亡率、白介素 6 浓度和儿茶酚胺需求量。该研究已在德国临床试验登记处注册（DRKS00021447）。2020年11月至2021年3月，入组了50名患者。23 名患者随机接受 CytoSorb 治疗，26 名患者接受标准护理。一名随机接受细胞因子吸附的患者因撤回知情同意而被排除。中位 5 天后（四分位距 [IQR]，4-5 天），CytoSorb 组 23 名患者中有 13 名患者（56.5%）观察到血管麻痹性休克消退，对照组 26 名患者中有 12 名患者（46.2%）出现血管麻痹性休克消退。4 天（IQR，3-5 天）。根据预定义变量年龄、性别、体外膜氧合治疗或从休克开始到纳入研究的时间进行调整后，主要终点的风险比 (HR) 为 HR，1.23（95% CI，0.54-2.79）；p = 0.63。CytoSorb 组的死亡率为 78%，对照组为 73%（未经调整的 HR，1.17 [95% CI，0.61–2.23]；p = 0.64）。各组之间对炎症标志物、儿茶酚胺需求以及不良事件类型和发生率的影响相似。

结论： 

在重症 COVID-19 患者中，CytoSorb 没有改善血管麻痹性休克的缓解或预定义的次要终点。