In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.
In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.
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DOI：
10.1097/cce.0000000000000202
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发表时间：
2020-09
影响因子：
--
通讯作者：
Bates DG
中科院分区：
文献类型：
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作者：
Das A;Saffaran S;Chikhani M;Scott TE;Laviola M;Yehya N;Laffey JG;Hardman JG;Bates DG
补充数字内容可在文本中找到。冠状病毒病2019急性呼吸窘迫综合征患者似乎至少呈现两种不同的表型：严重低氧血症，肺顺应性和肺气体体积相对保存良好（1型）和更传统的急性呼吸窘迫综合征表型，显示出“婴儿肺”的典型特征（2型）。我们的目的是测试关于冠状病毒病2019急性呼吸窘迫综合征的病理生理机制的合理假设，并评估其对预防管理的影响。我们采用了一种高保真计算模拟器，该模拟器先前在几项急性呼吸窘迫综合征研究中得到验证，以：1）定量了解冠状病毒病2019急性呼吸窘迫综合征与传统急性呼吸窘迫综合征之间的关键病理生理差异，2）评估不同呼气末正压，Fio 2和潮气量设置的影响。系统医学研究网络中的跨学科合作。该模拟器经过校准，以代表接受有创机械通气的冠状病毒病2019急性呼吸窘迫综合征患者，这些患者的体重指数正常和升高。一个也没有。实施缺氧性肺血管收缩和血管舒张中断导致塌陷肺区域过度灌注的急性呼吸窘迫综合征模型未能复制2019年1型冠状病毒病急性呼吸窘迫综合征患者的临床数据。增加机制以反映由于肺炎的影响而导致的肺泡气体交换中断和由于微血栓的出现而导致的血管阻力增加，产生了与2019年1型冠状病毒病急性呼吸窘迫综合征患者的数据一致的通气灌注不匹配和低氧血症水平，同时保持了接近正常的肺顺应性和气体容量。对于这种1型冠状病毒病2019急性呼吸窘迫综合征模型，在一系列测量中观察到对5至15 cm H2O之间呼气末正压增量的非典型反应：增加呼气末正压导致肺顺应性降低，氧合没有改善，而机械功率，驱动压力和平台压力都增加。基于急性呼吸窘迫综合征网络协议的不同呼气末正压水平的fio 2设置不足以实现充分的氧合。潮气量从5 mL/kg增加到10 mL/kg，在1型冠状病毒病2019急性呼吸窘迫综合征模型中，呼吸机诱导的肺损伤的多个指标增加与传统急性呼吸窘迫综合征模型中观察到的增加相似。我们的模型表明，使用标准呼气末正压/Fio 2表、更高的呼气末正压策略和更高的潮气量都可能对1型冠状病毒病2019急性呼吸窘迫综合征患者有害，建议采用高度个性化的治疗方法。
Supplemental Digital Content is available in the text. Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the “baby lung” (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. Interdisciplinary Collaboration in Systems Medicine Research Network. The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. None. An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.