Kheirabadi Bijan Shams, Mace James E, Terrazas Irasema B, Fedyk Chriselda G, Valdez Krystal K, MacPhee Martin J, Beall Dawson, Estep J Scot, Dubick Michael A, Blackbourne Lorne H
Hemostasis Division, US Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.
J Trauma. 2010 Nov;69(5):1062-72; discussion 1072-3. doi: 10.1097/TA.0b013e3181fa0f21.
Previous studies identified WoundStat (WS, smectite) and Combat Gauze (CG, kaolin-coated gauze) as the most effective available agents for controlling arterial bleeding with potential utility in casualty care. Tissue sealant properties of WS suggested its potential advantage over clot-promoting CG for treating coagulopathic bleeding. This study compared the efficacy of CG and WS with a fibrinogen-based (FAST) dressing to control bleeding in coagulopathic animals.
Coagulopathy was induced in pigs (n = 55, 35 kg) by ∼50% isovolemic hemodilution and hypothermia (core temperature, 33°C ± 0.5°C). A 6-mm arteriotomy was made in the femoral artery and free bleeding allowed for 30 seconds. A test agent (n = 13-15 per group) or control product (gauze, GZ, n = 12) was applied to the wounds and compressed with a Kerlix gauze for 2 minutes. Fluid resuscitation was given, titrated to a mean arterial pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Angiography using the computed tomography method was performed on survivors, and local tissues were collected for histology.
No differences were seen in baseline measures. Coagulopathy, confirmed by a 31% increase in prothrombin time and a 28% reduction in clotting strength (maximum amplitude, thrombelastography assay), was similar in all groups before injury. The average pretreatment blood loss was 11.9 mL/kg ± 0.4 mL/kg with no difference among groups. Posttreatment blood loss, however, was significantly different (p = 0.015) ranging from 18.2 mL/kg ± 8.8 mL/kg (FAST) to 63.3 mL/kg ± 10.2 mL/kg (GZ controls). Stable hemostasis was achieved in 10 of 13 (FAST), 5 of 15 (CG), 2 of 15 (WS), and 1 of 12 (GZ) animals in each group, resulting in significantly different survival rates (8-77%; p = 0.001). The average survival times were 145 (FAST), 119 (CG), 75 (WS), and 74 (GZ) minutes for different groups (p < 0.002). The outcomes with the FAST dressing were significantly better than with WS or GZ in this coagulopathic bleeding model. Essentially, no difference was found between WS and GZ control. Computed tomography images showed limited blood flow only through the vessels treated with FAST dressings. Histologic observations of the vessels indicated minimal damage with FAST and CG and greater injury with WS with some residues present on the tissues.
The tissue sealant property of WS is apparently mediated by clot formation in the wound; therefore, it was ineffective under coagulopathic conditions. CG was partially effective in maintaining blood pressure up to 1 hour after application. FAST dressing showed the highest efficacy because of the exogenous delivery of concentrated fibrinogen and thrombin to the wound, which bypasses coagulopathy and secures hemostasis.
先前的研究确定WoundStat（WS，蒙脱石）和Combat Gauze（CG，高岭土涂层纱布）是控制动脉出血最有效的现有药物，在伤员救治中具有潜在用途。WS的组织密封性能表明其在治疗凝血病性出血方面比促进凝血的CG具有潜在优势。本研究比较了CG、WS与基于纤维蛋白原的（FAST）敷料在控制凝血病动物出血方面的疗效。
通过约50%的等容血液稀释和低温（核心温度，33°C±0.5°C）在猪（n = 55，35 kg）中诱导凝血病。在股动脉上进行6毫米的动脉切开术，让血液自由流出30秒。将一种测试药物（每组n = 13 - 15）或对照产品（纱布，GZ，n = 12）应用于伤口，并用Kerlix纱布压迫2分钟。进行液体复苏，将平均动脉压滴定至65毫米汞柱。观察动物180分钟或直至死亡。对存活的动物使用计算机断层扫描方法进行血管造影，并收集局部组织进行组织学检查。
基线测量无差异。所有组在受伤前的凝血病情况相似，凝血酶原时间增加31%和凝血强度降低28%（血栓弹力图测定的最大振幅）证实了这一点。预处理时的平均失血量为11.9 mL/kg±0.4 mL/kg，各组之间无差异。然而，治疗后的失血量有显著差异（p = 0.015），范围从18.2 mL/kg±8.8 mL/kg（FAST）到63.3 mL/kg±10.2 mL/kg（GZ对照）。每组中，13只（FAST）中的10只、(CG) 15只中的5只、(WS) 15只中的2只和12只（GZ）中的1只动物实现了稳定止血，导致存活率有显著差异（8 - 77%；p = 0.001）。不同组的平均存活时间分别为145分钟（FAST）、119分钟（CG）、75分钟（WS）和74分钟（GZ）（p < 0.002）。在这种凝血病性出血模型中，FAST敷料的效果明显优于WS或GZ。本质上，WS和GZ对照之间没有发现差异。计算机断层扫描图像显示只有通过FAST敷料处理的血管有有限的血流。对血管的组织学观察表明，FAST和CG造成的损伤最小，而WS造成的损伤更大，组织上有一些残留物。
WS的组织密封性能显然是由伤口中的凝血形成介导的；因此，在凝血病条件下它是无效的。CG在应用后长达1小时内对维持血压有部分效果。FAST敷料显示出最高的疗效，因为它将浓缩的纤维蛋白原和凝血酶外源性输送到伤口，绕过了凝血病并确保了止血。
