危重型新型冠状病毒肺炎有创机械通气患者炎性细胞因子水平的变化分析

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目的:探讨危重型新型冠状病毒肺炎(新冠肺炎)有创机械通气(IMV)患者炎性细胞因子水平变化及与预后的关系。方法:2020年2月4日至3月25日内蒙古医科大学附属医院援鄂医疗队在援鄂期间整建制接管华中科技大学同济医学院附属协和医院西院重症监护病房(ICU),救治接受IMV的危重型新冠肺炎患者43例。回顾性分析患者的临床资料,包括一般资料、病程及住院期间临床转归,记录患者IMV前48 h、IMV后48 h及脱机后48 h或死亡前最后一次炎性细胞因子水平,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回归分析筛选影响患者住院期间死亡的独立危险因素。结果:43例患者中病情好转13例,死亡30例。与存活组比较,死亡组患者年龄更大(岁:67.6±7.3比58.5±11.9,n P<0.05),合并高血压、糖尿病和冠心病的比例更高(53.3%比15.4%,63.3%比23.1%,26.7%比0%,均n P<0.05),发病至入院、入ICU时间及行IMV时间更长(d:分别为9.17±5.00比5.07±2.49、17.10±7.11比12.23±5.05、17.90±7.46比12.61±5.60,均n P<0.05)。死亡组患者IMV后IL-6和TNF-α水平较IMV前48 h和好转组均显著升高,尤其是IL-6水平明显高于好转组IMV后48 h和脱机后48 h 〔ng/L:800.00 (194.25,2 000.00)比22.03(6.66,28.21),3 204.00(1 264.88,5 000.00)比5.00(3.98,12.27),均n P<0.01〕。死亡组患者死亡前最后一次IL-10水平明显高于好转组脱机后48 h 〔ng/L:55.89(26.07,100.14)比3.53 (2.76,12.36),n P<0.05〕。两组各时间点IL-2和IL-4水平比较差异均无统计学意义。将患者年龄、基础疾病、IMV后IL-6水平纳入多因素非条件Logistic回归分析,结果显示,年龄〔优势比(n OR)=0.821,95%可信区间(95%n CI)为0.695~0.968〕和合并高血压(n OR=0.027,95%n CI为0.002~0.378)、糖尿病(n OR=0.054,95%n CI为0.005~0.611)、冠心病(n OR=0.042,95%n CI为0.002~0.968)等基础疾病以及IMV后的IL-6水平(n OR=0.902,95%n CI为0.819~0.994)是危重型新冠肺炎IMV患者住院期间死亡的独立危险因素(均n P<0.05)。n 结论:危重型新冠肺炎IMV患者炎性细胞因子IL-6、IL-10和TNF-α水平均随病情加重而升高,以IL-6升高最明显;IL-6是危重型新冠肺炎IMV患者住院期间死亡的独立危险因素。“,”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, n 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 n 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 n 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 n 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), n 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 ( n OR) = 0.821, 95% confidence interval (95%n CI) was 0.695-0.968], hypertension (n OR = 0.027, 95%n CI was 0.002-0.378), diabetes mellitus (n OR = 0.054, 95%n CI was 0.005-0.611), coronary heart disease (n OR = 0.042, 95%n CI was 0.002-0.968) and the IL-6 level after IMV (n OR = 0.902, 95%n CI was 0.819-0.994) were independent risk factors for death during hospitalization in patients with critical COVID-19 undergoing IMV (all n P < 0.05).n 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.
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