MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.
MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.
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DOI：
10.1002/rth2.12669
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发表时间：
2022-03
影响因子：
4.6
通讯作者：
Yaffe MB
中科院分区：
文献类型：
--
作者：
Barrett CD;Moore HB;Moore EE;Benjamin Christie D 3rd;Orfanos S;Anez-Bustillos L;Jhunjhunwala R;Hussain S;Shaefi S;Wang J;Hajizadeh N;Baedorf-Kassis EN;Al-Shammaa A;Capers K;Banner-Goodspeed V;Wright FL;Bull T;Moore PK;Nemec H;Thomas Buchanan J;Nonnemacher C;Rajcooar N;Ramdeo R;Yacoub M;Guevara A;Espinal A;Hattar L;Moraco A;McIntyre R;Talmor DS;Sauaia A;Yaffe MB
一旦出现严重的 COVID-19 呼吸衰竭，目前几乎没有治疗方法。鉴于 COVID-19 患者尸检研究中已知弥漫性肺微血栓，我们假设组织纤溶酶原激活剂 (tPA) 可能会改善 COVID-19 呼吸衰竭的肺功能。对确诊为 COVID-19 并患有严重呼吸衰竭且接受全身 tPA（阿替普酶）治疗的患者进行了一项多中心、回顾性、观察性研究。经机构审查委员会批准后，来自七个医疗中心的 79 名成年人被纳入最终分析； 23 例被排除在分析之外，因为 tPA 是用于治疗肺大栓塞或深静脉血栓形成。主要结果是 tPA 后 48 小时 PaO2/FiO2 比值从基线改善。使用线性混合模型进行分析。 tPA 与 48 小时时 PaO2/FiO2 显着改善相关（估计配对差异 = 23.1 ± 6.7），并持续到 72 小时（交互作用项 p < 0.00）。 tPA 给药还与接受 tPA 后 24、48 和 72 小时国家早期预警评分 2 分数的提高相关（交互作用项 p = 0.00）。 tPA 后 D-二聚体立即显着升高，与形成的凝块溶解一致。与呼吸状态较差但稳定（未下降）的患者相比，tPA 给药前呼吸状态下降的患者 PaO2/FiO2 比率有更显着的改善。给予 tPA 后 24 小时内发生 1 例颅内出血。这些数据表明，tPA 与严重 COVID-19 呼吸衰竭患者肺功能的显着改善相关，尤其是肺功能下降的患者，并且在该患者群体中具有可接受的安全性。
Few therapies exist to treat severe COVID‐19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID‐19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID‐19 respiratory failure. A multicenter, retrospective, observational study of patients with confirmed COVID‐19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy‐nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p = 0.00). D‐dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO2/FiO2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration. These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID‐19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.
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DOI：
10.1164/rccm.201804-0692oc
发表时间：
2019-02-01
影响因子：
24.7
作者：
Sinha, Pratik;Calfee, Carolyn S.;Kallet, Richard H.
通讯作者：
Kallet, Richard H.
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
DOI：
10.1016/s0140-6736(20)32008-0
发表时间：
2020-10-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
Barbaro RP;MacLaren G;Boonstra PS;Iwashyna TJ;Slutsky AS;Fan E;Bartlett RH;Tonna JE;Hyslop R;Fanning JJ;Rycus PT;Hyer SJ;Anders MM;Agerstrand CL;Hryniewicz K;Diaz R;Lorusso R;Combes A;Brodie D;Extracorporeal Life Support Organization
通讯作者：
Extracorporeal Life Support Organization
影响因子：
4.6
作者：
Moore, Hunter B.;Barrett, Christopher D.;Yaffe, Michael B.
通讯作者：
Yaffe, Michael B.
影响因子：
8.4
作者：
Wardlaw, Joanna M.;Murray, Veronica;Berge, Eivind;del Zoppo, Gregory J.
通讯作者：
del Zoppo, Gregory J.