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[2019 冠状病毒病危重症患者有创机械通气时炎症细胞因子水平变化分析]

[Analysis of the changes of inflammatory cytokine levels in patients with critical coronavirus disease 2019 undergoing invasive mechanical ventilation].

作者信息

Shan Hongwei, Lyu Zheng, Xiao Yan, Li Chunyang, Wang Jian, He Liping, Chen Fengying

机构信息

Department of Emergency, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia Autonomous Region, China.

Department of Critical Care Medicine, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430000, Hubei, China.

出版信息

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020 Sep;32(9):1051-1055. doi: 10.3760/cma.j.cn121430-20200414-00519.

DOI:10.3760/cma.j.cn121430-20200414-00519
PMID:33081889
Abstract

OBJECTIVE

To investigate the relationship between the changes of inflammatory cytokine levels and prognosis of patients with critical coronavirus disease 2019 (COVID-19) undergoing invasive mechanical ventilation (IMV).

METHODS

A retrospective study was conducted. The clinical date of critical COVID-19 patients undergoing IMV who were hospitalized in Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 4th to March 25th in 2020 were collected. At the same time, the inflammatory cytokine levels including interleukins (IL-2, IL-4, IL-6, IL-10) and tumor necrosis factor-α (TNF-α) at 48 hours before IMV and 48 hours after IMV of all the patients, as well as the 48 hours after weaning or right before death were recorded. Multivariate unconditional Logistic regression analysis was used to screen the independent risk factors of death during hospitalization.

RESULTS

Among the 43 patients, 13 patients improved and 30 died. Compared with the survival group, the patients in the non-survival group were older (years old: 67.6±7.3 vs. 58.5±11.9, P < 0.05), with higher rates of hypertension, diabetes and coronary heart disease (53.3% vs. 15.4%, 63.3% vs. 23.1%, 26.7% vs. 0%, all P < 0.05), and the time from onset to admission to hospital, admission to ICU and IMV were longer (days: it was 9.17±5.00 vs. 5.07±2.49, 17.10±7.11 vs. 12.23±5.05, and 17.90±7.46 vs. 12.61±5.60, respectively, all P < 0.05). The IL-6 and TNF-α levels on 48 hours after IMV in the non-survival patients increased significantly as compared with those before 48 hours and the surviving patients. Especially, the IL-6 levels increased significantly as compared with those at 48 hours after IMV and 48 hours after weaning in the surviving patients [ng/L: 800.00 (194.25, 2 000.00) vs. 22.03 (6.66, 28.21), 3 204.00 (1 264.88, 5 000.00) vs. 5.00 (3.98, 12.27), both P < 0.01]. The IL-10 level before death in the non-survival patients increased significantly as compared with that at 48 hours after weaning in the surviving patients [ng/L: 55.89 (26.07, 100.14) vs. 3.53 (2.76, 12.36), P < 0.05]. There were no significant differences in the levels of IL-2 and IL-4 between the two groups at every time point. The variables of age, basic diseases, the IL-6 level after IMV were included in the multivariate unconditional Logistic regression analysis, which showed that age [odds ratio (OR) = 0.821, 95% confidence interval (95%CI) was 0.695-0.968], hypertension (OR = 0.027, 95%CI was 0.002-0.378), diabetes mellitus (OR = 0.054, 95%CI was 0.005-0.611), coronary heart disease (OR = 0.042, 95%CI was 0.002-0.968) and the IL-6 level after IMV (OR = 0.902, 95%CI was 0.819-0.994) were independent risk factors for death during hospitalization in patients with critical COVID-19 undergoing IMV (all P < 0.05).

CONCLUSIONS

The levels of inflammatory cytokine including IL-6, IL-10, and TNF-α increased significantly with aggravation in critical COVID-19 patients undergoing IMV, especially IL-6. IL-6 was an independent risk factor for death of critical COVID-19 patients undergoing IMV.

摘要

目的

探讨2019冠状病毒病(COVID-19)危重症患者接受有创机械通气(IMV)时炎症细胞因子水平变化与预后的关系。

方法

进行一项回顾性研究。收集2020年2月4日至3月25日在华中科技大学同济医学院附属武汉协和医院住院接受IMV的COVID-19危重症患者的临床资料。同时记录所有患者IMV前48小时、IMV后48小时以及撤机后48小时或死亡前48小时的炎症细胞因子水平,包括白细胞介素(IL-2、IL-4、IL-6、IL-10)和肿瘤坏死因子-α(TNF-α)。采用多因素非条件Logistic回归分析筛选住院期间死亡的独立危险因素。

结果

43例患者中,13例好转,30例死亡。与存活组相比,非存活组患者年龄更大(岁:67.6±7.3 vs. 58.5±11.9,P<0.05),高血压、糖尿病和冠心病发生率更高(53.3% vs. 15.4%,63.3% vs. 23.1%,26.7% vs. 0%,均P<0.05),从发病到入院、入院到重症监护病房(ICU)和接受IMV的时间更长(天:分别为9.17±5.00 vs. 5.07±2.49,17.10±7.11 vs. 12.23±5.05,17.90±7.46 vs. 12.61±5.60,均P<0.05)。非存活患者IMV后48小时的IL-6和TNF-α水平较IMV前48小时及存活患者显著升高。尤其是,与存活患者IMV后48小时及撤机后48小时相比,非存活患者的IL-6水平显著升高[ng/L:800.00(194.25,2000.00)vs. 22.03(6.66,28.21),3204.00(1264.88,5000.00)vs. 5.00(3.98,12.27),均P<0.01]。非存活患者死亡前的IL-10水平较存活患者撤机后48小时显著升高[ng/L:55.89(26.07,100.14)vs. 3.53(2.76,12.36),P<0.05]。两组在各时间点的IL-2和IL-4水平无显著差异。将年龄、基础疾病、IMV后IL-6水平等变量纳入多因素非条件Logistic回归分析,结果显示年龄[比值比(OR)=0.821,95%置信区间(95%CI)为0.695 - 0.968]、高血压(OR = 0.027,95%CI为0.002 - 0.378)、糖尿病(OR = 0.054,95%CI为0.005 - 0.611)、冠心病(OR = 0.042,95%CI为0.002 - 0.968)以及IMV后IL-6水平(OR = 0.902,95%CI为0.819 - 0.994)是接受IMV的COVID-19危重症患者住院期间死亡的独立危险因素(均P<0.05)。

结论

接受IMV的COVID-19危重症患者中,包括IL-6、IL-10和TNF-α在内的炎症细胞因子水平随病情加重显著升高,尤其是IL-6。IL-6是接受IMV的COVID-19危重症患者死亡的独立危险因素。

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