Microvascular Flow Alteration and Endothelial Dysfunction in Critically Ill Patient With Covid-19
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in Microvascular flow index (MFI)
研究概览
简要总结
Microcirculatory dysfunction appears to play a key role in the development of organ failure leading to the death of patients with coronavirus disease 2019 (Covid-19). It is still uncertain today whether this damage is secondary to direct viral infection of endothelial cells or the consequence of the inappropriate inflammatory response induced by the infection. The analysis of endothelial and microcirculatory dysfunctions and glycocalyx degradation therefore appears to be necessary in the understanding of the pathophysiological mechanisms of Covid sepsis and could play a role in the evaluation of the efficacy of certain therapeutics which would aim at improving regional perfusion by decreasing microcirculatory dysfunction.However, the analysis of microcirculatory failure, endothelial dysfunction and glycocalyx degradation has so far only been evaluated in small cohorts, without quantitative analysis of microcirculatory perfusion
详细描述
The study of pathophysiological mechanisms of cellular penetration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) allows the understanding of organ failures observed in COVID 19. In order to allow its fusion with the cell membrane, SARS-Cov-2 must bind the Angiotensin Converting Enzyme 2 (ACE2) via its Spike protein. This process requires the priming of the viral S protein by a cellular serine protease TMPRSS2. Thus, any cell co-expressing these two receptors is a potential target for the virus. Among all the cells for which this co-expression could be observed, endothelial cells and vascular pericytes seem to be potential targets, whose infection could lead to the development of an endothelial dysfunction responsible for microcirculatory dysfunction. In addition, inappropriate host immune system response observed in Covid-19 with massive production of pro-inflammatory cytokines as IL-6, TNF α and VEGF could lead to endothelial dysfunction through neutrophils, monocytes and macrophages mobilization producing Reactive Oxygen Species that increase endothelium and glycocalyx damages. The resulting pro-adhesive, pro-vasoconstricting and prothrombotic effects could lead to vascular micro-thrombosis, capillary plugging and impairment of capillary flow.
Whether endothelial dysfunction is caused by direct viral cell infection or pro-inflammatory response is uncertain, but various studies have confirmed that endotheliopathy plays a key role in pathophysiological mechanisms in Covid 19.
In the context of critical care, the evaluation of microcirculatory perfusion appears to be a diagnostic tool of major importance. Indeed, microcirculatory dysfunction is directly associated with increased organ failure and mortality in the ICU. In addition, many clinical situations such as sepsis or hemorrhagic shock may be responsible for a loss of hemodynamic coherence between macro and microcirculatory parameters. Thus, the correction of macrohemodynamic parameters (arterial pressure, cardiac output, plasma lactate, central venous oxygen saturation) may be associated with persistent microcirculatory hypoperfusion. It thus appears essential to develop systems for assessing the microcirculation in order to move towards resuscitation guided by microcirculatory objectives.
The aim of this study is to describe the sublingual microcirculation and to evaluate endothelial dysfunction in critically ill patient with Covid-19, and to determine whether there is a correlation between the severity of microcirculatory damage, endothelial dysfunction and clinically important outcomes in ICU. The data will serve to develop strategies for individualized management of high-risk patients screened with microcirculation evaluation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patient (≥ 18 ans)
- •Affiliation to the French social security system
- •Patient admitted to ICU within 72 hours before inclusion
- •Patient presenting SARS-CoV-2 pneumonia diagnosed by CT scan or by COVID-19 PCR test
排除标准
- •Lesions of the oral mucosa
结局指标
主要结局
Change in Microvascular flow index (MFI)
时间窗: At admission, on day 1 and day 2
Change in a semi quantitative score evaluating the sublingual microcirculation using an incident dark field imaging device (Microscan, MicroVision Medical ) over the first days of ICU stay
次要结局
- Acute kidney injury(Day 28)
- Change in plasma Angiopoietin-2 levels (in ng/ml)(At admission, on day 1 and day 2)
- Change in perfused vessel density(At admission, on day 1 and day 2)
- Change in plasma Syndecan-1 levels (in pg/ml)(At admission, on day 1 and day 2)
- Change in plasma VEGF-A levels (in arbitrary units/ml)(At admission, on day 1 and day 2)
- Change in plasma Thrombomodulin levels (in arbitrary units/ml)(At admission, on day 1 and day 2)
- Change in cardiac output(At admission, on day 1 and day 2)
- Invasive Mechanical ventilation(Day 28)
- Blood C Reactive Protein levels (in mg/l)(At admission)
- Blood D-dimer levels (in µg/l)(At admission)
- Neutrophil to Lymphocyte ratio(At admission)
- The percentage of pulmonary lesions as assessed by computerized tomography (CT) scan(At admission)
- Mortality(Day 28)
- Length of stay in the ICU(Day 28)
- Organ failure(Every day from Day 0 to Day 8, and at Day 28 after inclusion)
- The ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2)(At admission)