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接受白细胞介素-6受体阻滞剂治疗的2019冠状病毒病急性呼吸窘迫综合征机械通气患者的白细胞介素-6轨迹与继发感染

Interleukin-6 Trajectory and Secondary Infections in Mechanically Ventilated Patients With Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Treated With Interleukin-6 Receptor Blocker.

作者信息

Vazquez Guillamet M Cristina, Kulkarni Hrishikesh S, Montes Kevin, Samant Maanasi, Shaikh Preet A, Betthauser Kevin, Mudd Philip A, Reynolds Daniel, O'Halloran Jane, Lyons Patrick, McEvoy Colleen, Vazquez Guillamet Rodrigo

机构信息

John T. Milliken Department of Medicine, Washington University, St Louis, MO.

Barnes Jewish Hospital, St Louis, MO.

出版信息

Crit Care Explor. 2021 Feb 3;3(2):e0343. doi: 10.1097/CCE.0000000000000343. eCollection 2021 Feb.

Abstract

UNLABELLED

To describe the infectious complications and interleukin-6 trajectories in mechanically ventilated patients with coronavirus disease 2019.

DESIGN

Retrospective cohort study.

SETTING

ICUs at Washington University-Barnes Jewish Hospital in St. Louis, MO.

PARTICIPANTS

All consecutive patients admitted to the medical ICU and requiring mechanical ventilation from March 12, 2020, to April 21, 2020, were included.

INTERVENTIONS

Tocilizumab, an interleukin-6 receptor blocker, was prescribed at the discretion of the treating physicians to patients with a clinical picture compatible with cytokine release syndrome.

MEASUREMENTS

All the patients were followed to death or hospital discharge. Demographic and laboratory data were collected retrospectively from the electronic medical record. Interleukin-6 levels were measured at days 0, 3, 7, 14, and 21. Infections were divided into culture positive and culture negative (clinically suspected and treated). The main outcomes were infectious complications and interleukin-6 levels at different points in time.

RESULTS

Forty-three patients with respiratory failure secondary to coronavirus disease 2019 were on mechanical ventilation during the study period. Twenty-seven (68%) were male, and 31 (72.1%) were African-American. Median Charlson score was 2 (interquartile range, 0-4). Median Pao2/Fio2 was 171.5 (122-221) on the day of mechanical ventilation initiation, and 13 patients (30.2%) required vasopressors. C-reactive protein was 142.7 (97.7-213.7), d-dimer 1,621 (559-13,434), and Acute Physiology and Chronic Health Evaluation-II 11 (9-15). Interleukin-6 levels at admission were 61 pg/mL (interquartile range, 28.6-439 pg/mL). Patients treated with tocilizumab had higher levels of interleukin-6 at each measurement (days 0, 3, 7, 14, and 21) compared with patients receiving standard of care. Both groups reached peak interleukin-6 levels at day 7. Administration of tocilizumab was associated with a trend toward increased risk of infection.

CONCLUSIONS

Interleukin-6 levels peak at day 7 in patients with severe coronavirus disease 2019 pneumonia requiring mechanical ventilation and follows a similar trajectory in patients with coronavirus disease 2019 pneumonia requiring mechanical ventilation irrespective of treatment with interleukin-6R blockers. Interleukin-6 levels continued to rise in nonsurvivors, in comparison with survivors, where the rise in interleukin-6 levels was followed by a decline.

摘要

未标注

描述2019冠状病毒病机械通气患者的感染并发症和白细胞介素-6变化轨迹。

设计

回顾性队列研究。

地点

密苏里州圣路易斯市华盛顿大学巴恩斯犹太医院重症监护病房。

参与者

纳入2020年3月12日至2020年4月21日期间入住内科重症监护病房并需要机械通气的所有连续患者。

干预措施

治疗医生酌情为临床表现符合细胞因子释放综合征的患者开具白细胞介素-6受体阻滞剂托珠单抗。

测量指标

对所有患者随访至死亡或出院。从电子病历中回顾性收集人口统计学和实验室数据。在第0、3、7、14和21天测量白细胞介素-6水平。感染分为培养阳性和培养阴性(临床疑似并接受治疗)。主要结局是不同时间点的感染并发症和白细胞介素-6水平。

结果

在研究期间,43例继发于2019冠状病毒病的呼吸衰竭患者接受了机械通气。27例(68%)为男性,31例(72.1%)为非裔美国人。Charlson评分中位数为2(四分位间距,0 - 4)。机械通气开始当天的氧合指数(Pao2/Fio2)中位数为171.5(122 - 221),13例患者(30.2%)需要血管活性药物支持。C反应蛋白为142.7(97.7 - 213.7),D - 二聚体为1621(559 - 13434),急性生理与慢性健康状况评分系统(APACHE-II)评分为11(9 - 15)。入院时白细胞介素-6水平为61 pg/mL(四分位间距,28.6 - 439 pg/mL)。与接受标准治疗的患者相比,接受托珠单抗治疗的患者在每次测量时(第0、3、7、14和21天)白细胞介素-6水平更高。两组均在第7天达到白细胞介素-6水平峰值。使用托珠单抗与感染风险增加的趋势相关。

结论

在需要机械通气的重症2019冠状病毒病肺炎患者中,白细胞介素-6水平在第7天达到峰值,且无论是否使用白细胞介素-6受体阻滞剂治疗,2019冠状病毒病肺炎机械通气患者的白细胞介素-6变化轨迹相似。与幸存者相比,非幸存者的白细胞介素-6水平持续升高,幸存者的白细胞介素-6水平升高后下降。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/797f/7861654/393dcb4b0223/cc9-3-e0343-g001.jpg

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