Division of Transplant Surgery, Department of Surgery, University of Colorado Denver, Denver, CO, USA.
Koch Institute for Integrative Cancer Research, Center for Precision Cancer Medicine, Departments of Biological Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
World J Emerg Surg. 2020 Apr 20;15(1):29. doi: 10.1186/s13017-020-00305-4.
COVID-19 threatens to quickly overwhelm our existing critical care infrastructure in the USA. Systemic tissue plasminogen activator (tPA) has been previously demonstrated to improve PaO/FiO (mmHg) when given to critically ill patients with acute respiratory distress syndrome (ARDS). It is unclear to what extent tPA may impact population-based survival during the current US COVID-19 pandemic.
A decision analytic Markov state transition model was created to simulate the life critically ill COVID-19 patients as they transitioned to either recovery or death. Two patient groups were simulated (50,000 patients in each group); (1) Patients received tPA immediately upon diagnosis of ARDS and (2) patients received standard therapy for ARDS. Base case critically ill COVID-19 patients were defined as having a refractory PaO/FiO of < 60 mmHg (salvage use criteria). Transition from severe to moderate to mild ARDS, recovery, and death were estimated. Markov model parameters were extracted from existing ARDS/COVID-19 literature.
The use of tPA was associated with reduced mortality (47.6% [tTPA] vs. 71.0% [no tPA]) for base case patients. When extrapolated to the projected COVID-19 eligible for salvage use tPA in the USA, peak mortality (deaths/100,000 patients) was reduced for both optimal social distancing (70.5 [tPA] vs. 75.0 [no tPA]) and no social distancing (158.7 [tPA] vs. 168.8 [no tPA]) scenarios.
Salvage use of tPA may improve recovery of ARDS patients, thereby reducing COVID-19-related mortality and ensuring sufficient resources to manage this pandemic.
COVID-19 有可能迅速使美国现有的重症监护基础设施不堪重负。先前已经证明,全身性组织纤溶酶原激活物(tPA)可改善急性呼吸窘迫综合征(ARDS)重症患者的 PaO/FiO(mmHg)。尚不清楚 tPA 在多大程度上可能影响当前美国 COVID-19 大流行期间的基于人群的生存率。
创建了决策分析马尔可夫状态转移模型,以模拟患有严重 COVID-19 的患者过渡到康复或死亡的过程。模拟了两组患者(每组 50,000 例):(1)患者在诊断为 ARDS 后立即接受 tPA;(2)患者接受 ARDS 的标准治疗。将基例严重 COVID-19 患者定义为难治性 PaO/FiO < 60mmHg(抢救使用标准)。估计了从严重到中度再到轻度 ARDS 的过渡、康复和死亡。从现有的 ARDS/COVID-19 文献中提取了马尔可夫模型参数。
对于基例患者,使用 tPA 可降低死亡率(47.6%[tTPA]比 71.0%[无 tPA])。当将其外推到预计可在美国使用抢救性 tPA 的 COVID-19 患者中时,在最佳社会隔离(70.5 [tPA]比 75.0 [无 tPA])和无社会隔离(158.7 [tPA]比 168.8 [无 tPA])两种情况下,峰值死亡率(每 10 万人死亡人数)均降低。
抢救性使用 tPA 可能会改善 ARDS 患者的康复,从而降低 COVID-19 相关死亡率,并确保有足够的资源来应对这一大流行。