经皮递送自行推进的含凝血酶粉末可提高凝血功能障碍和低体温猪模型中非压迫性躯干出血的存活率。
Percutaneous delivery of self-propelling thrombin-containing powder increases survival from noncompressible truncal hemorrhage in a swine model of coagulopathy and hypothermia.
机构信息
From the Michael Smith Laboratories, Department of Biochemistry and Molecular Biology (M.F.C., N.A.-M., H.Z.G., C.J.K.); School of Biomedical Engineering (M.F.C.); Department of Mechanical Engineering (H.Y., D.G.), The University of British Columbia, Vancouver, British Columbia, Canada; Blood Research Institute (H.Y., C.J.K.), Versiti; Departments of Surgery (H.Y., C.J.K.), Biochemistry (H.Y., C.J.K.), Biomedical Engineering (H.Y., C.J.K.), and Pharmacology and Toxicology (H.Y., C.J.K.), Medical College of Wisconsin, Milwaukee, Wisconsin; CoMotion Drug Delivery Systems (J.R.B.), Vancouver, British Columbia, Canada; Toronto Research Centre (H.P.), Defense Research and Development Canada; Department of Surgery (J.R.-N., A.B.), St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Emergency Medicine (N.J.W.), Harborview Medical Center, University of Washington, Seattle, Washington; and Suffield Research Centre (C.T., H.A.S.), Defense Research and Development Canada, Medicine Hat, Alberta, Canada.
出版信息
J Trauma Acute Care Surg. 2022 Aug 1;93(2S Suppl 1):S86-S93. doi: 10.1097/TA.0000000000003670. Epub 2022 May 23.
BACKGROUND
Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care. We previously reported that a self-propelling thrombin-containing powder (SPTP) can be delivered percutaneously into the abdomen as a minimally invasive intervention and can self-disperse through pooled blood to deliver the hemostatic agents thrombin and tranexamic acid locally to noncompressible intracavitary wounds. We hypothesized that, in swine with massive NCTH, dilutional coagulopathy, and hypothermia, delivering SPTP could extend survival times.
METHODS
Ten swine (n = 5 per group) underwent NCTH from a Grade V liver injury following a midline laparotomy. The laparotomy was closed with sutures afterwards, creating a hemoperitoneum, and animals were managed with crystalloid fluid resuscitation, or crystalloid resuscitation and SPTP. Self-propelling thrombin-containing powder was delivered into the closed abdomen using a CO 2 -powered spray device and a catheter placed into the hemoperitoneum, entering through the upper right quadrant using the Seldinger technique. Survival to 1 and 3 hours was recorded. In an additional animal, hemorrhage was created laparoscopically, and SPTP was imaged in situ within the abdomen to visually track dispersion of the particles.
RESULTS
Self-propelling thrombin-containing powder dispersed as far as 35 ± 5.0 cm within the abdomen. It increased survival to 1 and 3 hours (Kaplan-Meier p = 0.007 for both). The median survival time was 61 minutes with SPTP and 31 minutes without ( p = 0.016).
CONCLUSION
Self-propelling thrombin-containing powder effectively disperses medications throughout a hemoperitoneum and increases survival in a model of NCTH. It is a promising strategy for nonsurgical management of NCTH, warranting further testing of its safety and efficacy.
背景
非压迫性躯干出血（NCTH）仍然是战场上可预防死亡的主要原因。在受伤后第一小时内进行确定性治疗需要手术，但在从偏远和艰苦环境中撤离伤员时，这是困难的。在手术延迟期间，在院前进行的止血干预可以预防凝血功能障碍和出血性休克，并增加伤员存活以接受确定性治疗的可能性。我们之前报道过，一种自行推进的含凝血酶粉末（SPTP）可以经皮穿刺进入腹部作为一种微创干预措施，并且可以通过汇集的血液自行分散，将止血剂凝血酶和氨甲环酸局部输送到非压迫性的腔室内伤口。我们假设，在患有大量 NCTH、稀释性凝血功能障碍和低体温的猪中，给予 SPTP 可以延长存活时间。
方法
10 头猪（每组 5 头）通过中线剖腹术从 V 级肝损伤中发生 NCTH。剖腹术随后用缝线关闭，形成血腹，并通过晶体液复苏或晶体液复苏和 SPTP 进行管理。使用 CO 2 动力喷雾装置和通过 Seldinger 技术经右上象限进入的导管将自行推进的含凝血酶粉末输送到闭合的腹部。记录到 1 小时和 3 小时的存活时间。在另一只动物中，通过腹腔镜创建出血，并在腹部内原位对 SPTP 进行成像，以直观地跟踪颗粒的分散。
结果
自行推进的含凝血酶粉末在腹部内最远分散了 35±5.0 厘米。它增加了 1 小时和 3 小时的存活时间（Kaplan-Meier p = 0.007 用于两者）。SPTP 组的中位存活时间为 61 分钟，无 SPTP 组为 31 分钟（p = 0.016）。
结论
自行推进的含凝血酶粉末有效地在血腹内分散药物，并增加 NCTH 模型中的存活时间。它是 NCTH 非手术治疗的一种有前途的策略，需要进一步测试其安全性和有效性。
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