Alam Hasan B, Bice Leticia M, Butt Muhammad U, Cho S David, Dubick Michael A, Duggan Michael, Englehart Michael S, Holcomb John B, Morris Melanie S, Prince M Dale, Schreiber Martin A, Shults Christian, Sondeen Jill L, Tabbara Malek, Tieu Brandon H, Underwood Samantha A
Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts 02114, USA.
J Trauma. 2009 Oct;67(4):856-64. doi: 10.1097/TA.0b013e3181b5ae75.
Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model.
Yorkshire swine (40 +/- 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase = femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3x shed blood) + induction of hypothermia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase= liver packing. After liver packing, the animals (n = 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment.
At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy.
In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival.
创伤性凝血病、酸中毒和低温形成了一个“致命三联征”，难以治疗且与极高的死亡率相关。本研究在三个学术中心进行，以评估在复杂的多发伤模型中使用血液成分进行复苏是否能逆转凝血病。
约克夏猪（40±5千克）接受三阶段方案：（a）“院前”阶段=股骨骨折、出血（血容量的60%）、30分钟休克+输注生理盐水（3倍失血量）+诱导低温（33摄氏度）；（b）“早期医院”阶段=V级肝损伤；（c）“手术”阶段=肝填塞。肝填塞后，将动物（n = 60）随机分为以下组：（1）假手术操作和麻醉，无出血/损伤，（2）新鲜全血（FWB），（3）6%羟乙基淀粉（贺斯），（4）新鲜冰冻血浆/浓缩红细胞按1:1比例（1:1 FFP/PRBC），（5）单独使用FFP。治疗体积等于失血量。在实验期间及治疗后4小时监测血流动力学和生理参数以及凝血指标（血栓弹力图、凝血酶原时间、活化部分凝血活酶时间、国际标准化比值和血小板）。
在院前阶段结束时，动物出现了显著的酸中毒（乳酸>5 mmol/L且碱缺失>9 mmol/L）和凝血病。贺斯组和血液成分治疗组的治疗后死亡率分别为85%和0%（p<0.05）。使用血液制品（FWB、FFP和FFP:PRBC）治疗的组的血流动力学参数和生存率相似。与接受红细胞治疗的组（FWB和FFP:PRBC）相比，接受FFP和贺斯治疗的动物有显著贫血。FFP和FFP:PRBC治疗纠正凝血病的效果与FWB一样有效，而贺斯治疗使凝血病恶化。
在这个可重复的模型中，我们表明羟乙基淀粉会使创伤相关凝血病恶化，但通过给予血液成分可迅速逆转。令人印象深刻的是，即使没有任何红细胞，输注FFP也能纠正凝血病并导致良好的早期生存率。
