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托珠单抗治疗2019冠状病毒病相关危重症:一项倾向匹配分析

Tocilizumab in Coronavirus Disease 2019-Related Critical Illness: A Propensity Matched Analysis.

作者信息

Rajendram Prabalini, Sacha Gretchen L, Mehkri Omar, Wang Xiaofeng, Han Xiaozhen, Vachharajani Vidula, Duggal Abhijit

机构信息

Department of Critical Care, Cleveland Clinic, Cleveland, OH.

Department of Pharmacy, Cleveland Clinic, Cleveland, OH.

出版信息

Crit Care Explor. 2021 Jan 13;3(1):e0327. doi: 10.1097/CCE.0000000000000327. eCollection 2021 Jan.

Abstract

UNLABELLED

The primary objective was to evaluate ICU mortality at 28 days in patients with severe hypoxemic respiratory failure due to coronavirus disease 2019 infection who received tocilizumab. The secondary objectives were to evaluate ICU-, hospital-, mechanical ventilation-, and vasopressor-free days at day 28 and development of secondary infections.

DESIGN

Retrospective, observational, multicenter, cohort study between March 15, 2020, and May 31, 2020. Using propensity score matching based on ICU admission source, C-reactive protein, Sequential Organ Failure Assessment score, vasopressor use, age, race, weight, and mechanical ventilation, patients who received tocilizumab were matched to patients who did not receive tocilizumab.

SETTING

Ten hospitals within the Cleveland Clinic Enterprise.

PATIENTS

Adult patients admitted to a medical, surgical, neurosciences, or mixed ICU with severe acute respiratory syndrome coronavirus 2 infection.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Four-hundred forty-four patients were included: 342 patients (77%) did not receive tocilizumab and 102 patients (23%) received tocilizumab. Of those, 82 patients in each arm were matched. Before matching, patients who received tocilizumab had higher Sequential Organ Failure Assessment scores (6.1 ± 3.4 vs 4.7 ± 3.6), higher C-reactive protein (21.0 ± 10.2 vs 13.7 ± 9.6 mg/dL), higher frequency of intubation, vasopressor requirement, and paralytics. After matching, characteristics were more balanced and over 85% of patients required mechanical ventilation. ICU mortality was lower in tocilizumab group (23.2% vs 37.8%; risk difference, -15%; 95% CI, -29% to -1%), with more ICU-, hospital-, and vasoactive-free days at day 28 compared with those who did not receive tocilizumab. There was no difference in mechanical ventilation-free days at day 28 or development of secondary infections.

CONCLUSIONS

Tocilizumab use was associated with a significant decrease in ICU mortality in critically ill coronavirus disease 2019 patients with severe hypoxemic respiratory failure. Future randomized controlled trials limited to tocilizumab administration in critically ill coronavirus disease 2019 patients, with severe hypoxemic respiratory failure, are needed to support these findings.

摘要

未标注

主要目标是评估因2019年冠状病毒病感染导致严重低氧血症性呼吸衰竭且接受托珠单抗治疗的患者在28天时的重症监护病房(ICU)死亡率。次要目标是评估在第28天时的ICU无日、医院无日、机械通气无日和血管活性药物无日情况以及继发感染的发生情况。

设计

2020年3月15日至2020年5月31日期间进行的回顾性、观察性、多中心队列研究。基于ICU入院来源、C反应蛋白、序贯器官衰竭评估评分、血管活性药物使用情况、年龄、种族、体重和机械通气情况,采用倾向得分匹配法,将接受托珠单抗治疗的患者与未接受托珠单抗治疗的患者进行匹配。

地点

克利夫兰诊所企业内的10家医院。

患者

因严重急性呼吸综合征冠状病毒2感染入住内科、外科、神经科学或综合性ICU的成年患者。

干预措施

无。

测量指标及主要结果

共纳入444例患者:342例患者(77%)未接受托珠单抗治疗,102例患者(23%)接受托珠单抗治疗。其中,每组82例患者进行了匹配。匹配前,接受托珠单抗治疗的患者序贯器官衰竭评估评分更高(6.1±3.4对4.7±3.6)、C反应蛋白更高(21.0±10.2对13.7±9.6mg/dL)、插管频率、血管活性药物需求和使用麻痹剂的频率更高。匹配后,特征更为均衡,超过85%的患者需要机械通气。托珠单抗组的ICU死亡率更低(23.2%对37.8%;风险差异为-15%;95%CI为-29%至-1%),与未接受托珠单抗治疗的患者相比,在第28天时的ICU无日、医院无日和血管活性药物无日更多。在第28天时的机械通气无日情况或继发感染的发生方面没有差异。

结论

在患有严重低氧血症性呼吸衰竭的危重症2019年冠状病毒病患者中,使用托珠单抗与ICU死亡率显著降低相关。需要开展未来的随机对照试验,仅限于对患有严重低氧血症性呼吸衰竭的危重症2019年冠状病毒病患者给予托珠单抗治疗,以支持这些发现。

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