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皮质类固醇治疗与机械通气的新型冠状病毒肺炎相关急性呼吸窘迫综合征(ARDS)患者的死亡率:一项多中心队列研究

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study.

作者信息

Moreno Gerard, Carbonell Raquel, Martin-Loeches Ignacio, Solé-Violán Jordi, Correig I Fraga Eudald, Gómez Josep, Ruiz-Botella Manuel, Trefler Sandra, Bodí María, Murcia Paya Josefa, Díaz Emili, Vidal-Cortes Pablo, Papiol Elisabeth, Albaya Moreno Antonio, Sancho Chinesta Susana, Socias Crespi Lorenzo, Lorente María Del Carmen, Loza Vázquez Ana, Vara Arlanzon Rebeca, Recio María Teresa, Ballesteros Juan Carlos, Ferrer Ricard, Fernandez Rey Elisabeth, Restrepo Marcos I, Estella Ángel, Margarit Ribas Antonio, Guasch Neus, Reyes Luis F, Marín-Corral Judith, Rodríguez Alejandro

机构信息

Critical Care Department, Autonomous University of Barcelona (UAB), Joan XXIII University Hospital, C/ Dr Mallafrè Guasch, 4, 43005, Tarragona, Spain.

Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, Dublin, Ireland.

出版信息

Ann Intensive Care. 2021 Nov 26;11(1):159. doi: 10.1186/s13613-021-00951-0.

Abstract

BACKGROUND

Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients.

METHODS

This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis.

RESULTS

We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39-0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16-2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes.

CONCLUSIONS

Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

摘要

背景

关于皮质类固醇对重症2019冠状病毒病(COVID-19)患者的有效性,仍存在一些未解决的问题。我们旨在评估皮质类固醇对机械通气的COVID-19相关急性呼吸窘迫综合征(ARDS)患者在重症监护病房(ICU)死亡率的临床影响。

方法

这是一项对前瞻性收集的数据进行的回顾性研究,研究在70个ICU(68个西班牙的、1个安道尔的、1个爱尔兰的)中进行,纳入了2020年2月6日至9月20日期间收治的机械通气的COVID-19相关ARDS患者。排除因难治性休克接受皮质类固醇治疗的个体。通过倾向评分匹配,将入院时接受皮质类固醇治疗的患者与未接受皮质类固醇治疗的患者进行配对。主要结局是全因ICU死亡率。次要结局是比较皮质类固醇治疗组和非皮质类固醇治疗组患者的院内死亡率、28天无呼吸机天数、呼吸道二重感染以及住院时间。我们进行了考虑竞争风险的生存分析和亚组敏感性分析。

结果

我们纳入了1835例机械通气的COVID-19相关ARDS患者,其中1117例(60.9%)接受了皮质类固醇治疗。倾向评分匹配后,接受皮质类固醇治疗的患者和未接受治疗的患者的ICU死亡率没有差异(33.8%对30.9%;p = 0.28)。在生存分析中,ICU入院时接受皮质类固醇治疗与短期生存获益相关(风险比[HR] 0.53;95%置信区间[CI] 0.39 - 0.72),尽管在入院第17天之后,这种效果发生了转变,ICU死亡率增加(长期HR 1.68;95% CI 1.16 - 2.45)。敏感性分析强化了这些结果。年龄<60岁、重度ARDS以及皮质类固醇联合托珠单抗的亚组可能从皮质类固醇中获益最大,因为观察到短期ICU死亡率降低且无长期负面影响。在ICU和医院中,非幸存者中接受皮质类固醇治疗的患者住院时间更长。其余次要结局没有显著差异。

结论

我们的结果表明,皮质类固醇治疗对机械通气的COVID-19相关ARDS患者的ICU死亡率有双相时间依赖性影响。特定亚组在使用皮质类固醇时显示出对改善生存有明显效果。因此,需要进一步研究以确定机械通气的COVID-19相关ARDS患者中对治疗有反应的亚组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba2/8626551/b920b322c459/13613_2021_951_Fig1_HTML.jpg

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