Nates Joseph L, Cattano Davide, Chelly Jacques E, Doursout Marie-Françoise
Division of Anesthesiology and Critical Care, Department of Critical Care Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Anesthesiology, The University of Texas Medical School at Houston, Houston, TX.
Transl Res. 2015 May;165(5):549-57. doi: 10.1016/j.trsl.2014.09.002. Epub 2014 Sep 16.
Disseminated intravascular coagulation and fibrinolysis have been associated with lipopolysaccharide (LPS)-induced endotoxemic sepsis. It has been well established by point-of-care (POC) thrombelastography (TEG) that pigs have a hemocoagulation pathophysiology that resembles humans. We evaluated the use of TEG during the development of coagulation abnormalities in a porcine model of endotoxemia. After approval by the Animal Welfare Committee, pigs were instrumented to record hemodynamic variables. Ten days after surgical instrumentation, LPS (50 μg/kg) was infused intravenously over a period of 45 minutes in conscious animals. Hemodynamic parameters were recorded before and for 6 hours after LPS infusion was completed. Simultaneously, blood samples were analyzed using TEG to measure reaction time (R), clotting time (K), alpha angle (α), maximum amplitude (MA), coagulation index (CI), percent lysis at 30 minutes, and percent lysis at 60 minutes. LPS induced profound hemodynamic changes associated with the induced endotoxemia. Concomitantly, a progressive consumption coagulopathy characterized by significant increases in R and K and decreases in α, MA, and CI developed. The overall hemocoagulation profile of the 3 nonsurviving animals (27%) was significantly different than that of the survivors. Fibrinolysis was not detected during the 6-hour evaluation period. All stages of clot formation were affected as demonstrated by TEG (increased R and K, decreased α and MA). Our results suggest that TEG is a rapid method for assessing coagulation abnormalities in early stages of endotoxemia in pigs. TEG could have significant clinical applications as a rapid POC method in human patients with sepsis.
弥散性血管内凝血和纤维蛋白溶解与脂多糖(LPS)诱导的内毒素血症性脓毒症有关。即时检测(POC)血栓弹力图(TEG)已充分证实,猪的血液凝固病理生理学与人类相似。我们在内毒素血症猪模型的凝血异常发展过程中评估了TEG的应用。经动物福利委员会批准后,对猪进行仪器植入以记录血流动力学变量。手术植入仪器10天后,在清醒动物中于45分钟内静脉输注LPS(50μg/kg)。在LPS输注完成前及完成后6小时记录血流动力学参数。同时,使用TEG分析血样以测量反应时间(R)、凝血时间(K)、α角(α)、最大振幅(MA)、凝血指数(CI)、30分钟时的溶解百分比和60分钟时的溶解百分比。LPS诱导了与内毒素血症相关的显著血流动力学变化。同时,出现了以R和K显著增加以及α、MA和CI降低为特征的进行性消耗性凝血病。3只未存活动物(27%)的整体血液凝固情况与存活动物显著不同。在6小时评估期内未检测到纤维蛋白溶解。TEG显示凝血形成的所有阶段均受到影响(R和K增加,α和MA降低)。我们的结果表明,TEG是评估猪内毒素血症早期凝血异常的快速方法。TEG作为一种快速的即时检测方法,在脓毒症人类患者中可能具有重要的临床应用价值。