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在改性沸石中添加藻酸盐可改善致死性腹股沟损伤猪模型的止血性能。

Addition of an alginate to a modified zeolite improves hemostatic performance in a swine model of lethal groin injury.

作者信息

Li Jiang, Yan Wei, Jing Li, Xueyong Li, Yuejun Li, Wangzhou Li, Shaozong Chen

机构信息

Department of Plastics and Burns, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

J Trauma. 2009 Mar;66(3):612-20. doi: 10.1097/TA.0b013e318160ff4d.

DOI:10.1097/TA.0b013e318160ff4d
PMID:19276728
Abstract

BACKGROUND

QuikClot is a zeolite-based hemostatic agent that can control severe hemorrhage through adsorption of water in an exothermic reaction. Ion exchanging the calcium ions in zeolite type 5A with cations of a reduced hydration enthalpy can reduce heat generation, but its effect on the hemostatic efficacy is not clear. We developed a new compound zeolite hemostat and tested it against controls in a modified swine model of battlefield injury.

METHODS

A modified complex groin injury was created in 42 swine (39.4 +/- 2.6 kg). This included semitransection of the proximal thigh (level of inguinal ligament) and semidivision of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3) SD + zeolite hemostat (QC), (4) SD + chemically modified zeolite hemostat, where calcium was substituted with silver (Ag) and zinc (Zn) simultaneously, (Ag.Zn-zeolite), and (5) SD+ the compound hemostat composed of Ag.Zn-zeolite and alginate. Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch during 30 minutes). Survival for 180 minutes was the primary endpoint for this study. Blood loss, wound temperatures, and histologic tissue damage were recorded as well. In addition, the antibacterial activities of these hemostatic agents were tested on agar plates. At the end of experiment, the strength of clots was carefully measured by a Tablet Hardness Analyzer.

RESULTS

Mortality in the group treated with the application of the compound hemostat composed of Ag.Zn-zeolite and alginate was 10% versus 100% in the ND group and 71% in the SD group (p < 0.001 vs. ND group, p < 0.05 vs. SD group). The QC group had a mortality rate of 22%, whereas application of Ag- and Zn-substituted zeolite associated with a mortality rate of 37.5%. Ag and Zn substitution of zeolite reduced the in vivo temperature peak to 39.8 degrees C +/- 2.3 degrees C and no thermal injury of tissue was noted in these groups. Ag- and Zn-substituted zeolite posed an antibacterial ability against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Addition of an alginate into the modified zeolite hemostat reinforced the strength of clots to 18.52 N +/- 1.33 N.

CONCLUSIONS

Application of the compound zeolite hemostat can effectively control hemorrhage and dramatically reduce mortality from a lethal groin wound. In addition to its antibacterial properties, Ag- and Zn-substituted zeolite hemostat can decrease the exothermic reaction and greatly attenuate the heat-induced tissue injury.

摘要

背景

QuikClot是一种基于沸石的止血剂,可通过放热反应吸附水分来控制严重出血。用具有较低水合焓的阳离子对5A 型沸石中的钙离子进行离子交换可减少热量产生,但其对止血效果的影响尚不清楚。我们开发了一种新型复合沸石止血剂,并在改良的战场损伤猪模型中与对照进行了测试。

方法

对42头猪(39.4±2.6千克)造成改良的复杂腹股沟损伤。这包括大腿近端(腹股沟韧带水平)半横断以及股动脉和静脉半离断。3分钟后,将动物分为:(1)不进行包扎(ND);(2)标准包扎(SD);(3)SD+沸石止血剂(QC);(4)SD+化学改性沸石止血剂,其中钙同时被银(Ag)和锌(Zn)取代(Ag.Zn-沸石);(5)SD+由Ag.Zn-沸石和藻酸盐组成的复合止血剂。包扎后15分钟开始复苏(30分钟内输注500毫升6%羟乙基淀粉)。180分钟的存活情况是本研究的主要终点。还记录了失血量、伤口温度和组织学组织损伤情况。此外,在琼脂平板上测试了这些止血剂的抗菌活性。实验结束时,用片剂硬度分析仪仔细测量凝块强度。

结果

使用由Ag.Zn-沸石和藻酸盐组成的复合止血剂治疗的组死亡率为10%,而ND组为100%,SD组为71%(与ND组相比p<0.001,与SD组相比p<0.05)。QC组死亡率为22%,而应用Ag和Zn取代的沸石死亡率为37.5%。沸石的Ag和Zn取代使体内温度峰值降至39.8℃±2.3℃,且这些组未观察到组织热损伤。Ag和Zn取代的沸石对铜绿假单胞菌、金黄色葡萄球菌和大肠杆菌具有抗菌能力。在改性沸石止血剂中添加藻酸盐可将凝块强度增强至18.52 N±1.33 N。

结论

应用复合沸石止血剂可有效控制出血,并显著降低致命腹股沟伤口的死亡率。除了其抗菌特性外,Ag和Zn取代的沸石止血剂可减少放热反应,并大大减轻热诱导的组织损伤。

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