Martini Wenjun Z, Chinkes David L, Sondeen Jill, Dubick Michael A
US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234, USA.
Shock. 2006 Oct;26(4):396-401. doi: 10.1097/01.shk.0000228169.86845.29.
Hemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in fibrinogen metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9+/-0.8 kg) were anesthetized and instrumented with arterial and venous catheters and a thermodilution cardiac output catheter. Pigs were randomized into control (C; n=6), hemorrhage (H; n=6), and hemorrhage and resuscitation (H-LR; n=6) groups. Hemorrhage was induced by bleeding 35% of total blood volume for 30 min in H and H-LR groups. Resuscitation in H-LR group was performed using lactated Ringer's solution (LR) at 3 times the bled volume for 30 min. Fibrinogen metabolism was quantified using a primed constant infusion of 1-13C-phenylalanine (6 h) and d5-phenylalanine (4 h) and subsequent analysis by gas chromatograph-mass spectrometry, together with measurements of hemodynamics (hourly) and coagulation by thromboelastography (at baseline and 4 h after hemorrhage and resuscitation). Hemorrhage caused decreases in arterial pH and base excess, and an increase in arterial lactate content. Fluid resuscitation corrected these changes toward normal levels. Fibrinogen level was unchanged in C and decreased to 76%+/-4% in H and to 73%+/-3% in H-LR (both P<0.05, compared with baseline) after hemorrhage and resuscitation. Fibrinogen breakdown was increased from 3.0+/-0.4 mg kg-1 h-1 in C to 5.4+/-0.6 mg kg-1 h-1 in H and to 5.6+/-0.5 mg kg-1 h-1 in H-LR (both P<0.05, compared with control), but synthesis was unchanged. The clotting reaction time was unchanged in C and shortened to 93%+/-3% in H and to 91%+/-1% in H-LR (both P<0.05, compared with baseline). We conclude that hemorrhagic shock caused accelerated fibrinogen breakdown and coagulation. The LR resuscitation reduced tissue hypoxia indexes but did not affect the changes in fibrinogen metabolism and coagulation from hemorrhage. Thus, effective treatment of hemorrhage should include combining standard-of-care resuscitation with interventions to correct alterations in coagulation.
出血性凝血病是创伤后一种严重的并发症，其许多潜在机制仍不清楚。我们研究了中度出血和复苏后纤维蛋白原代谢及凝血的变化。将雌雄不限（体重40.9±0.8 kg）的猪麻醉，并插入动脉和静脉导管以及热稀释心输出量导管。将猪随机分为对照组（C；n = 6）、出血组（H；n = 6）和出血复苏组（H-LR；n = 6）。H组和H-LR组通过抽取35%的总血容量持续30分钟来诱导出血。H-LR组使用乳酸林格氏液（LR）以失血体积的3倍进行30分钟的复苏。使用1-13C-苯丙氨酸（6小时）和d5-苯丙氨酸（4小时）的预充式持续输注对纤维蛋白原代谢进行定量，随后通过气相色谱-质谱分析，并同时测量血流动力学（每小时一次）以及通过血栓弹力图测量凝血情况（在基线、出血和复苏后4小时）。出血导致动脉血pH值和碱剩余降低，动脉血乳酸含量升高。液体复苏使这些变化恢复到正常水平。出血和复苏后，C组纤维蛋白原水平未变，H组降至76%±4%，H-LR组降至73%±3%（与基线相比，两者P<0.05）。纤维蛋白原分解从C组的3.0±0.4 mg·kg-1·h-1增加到H组的5.4±0.6 mg·kg-1·h-来增加到H-LR组的5.6±0.5 mg·kg-1·h-1（与对照组相比，两者P<0.05），但合成未变。凝血反应时间在C组未变，在H组缩短至93%±3%，在H-LR组缩短至91%±1%（与基线相比，两者P<0.05）。我们得出结论，出血性休克导致纤维蛋白原分解加速和凝血加快。LR复苏降低了组织缺氧指标，但不影响出血引起的纤维蛋白原代谢和凝血变化。因此，有效的出血治疗应包括将标准的复苏治疗与纠正凝血改变的干预措施相结合。
