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壳聚糖基 lifefoam 提高猪致死性非压迫性腹部出血的存活率。

Chitosan-based lifefoam improves survival in lethal noncompressible abdominal bleeding in swine.

机构信息

Division of Trauma, Emergency Surgery & Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, MA.

Division of Trauma, Emergency Surgery & Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, MA.

出版信息

Surgery. 2022 Jul;172(1):421-426. doi: 10.1016/j.surg.2022.01.016. Epub 2022 Feb 17.

DOI:10.1016/j.surg.2022.01.016
PMID:35184891
Abstract

BACKGROUND

In military combat settings, noncompressible closed cavity exsanguination is the leading cause of potentially survivable deaths, with no effective treatment available at point of injury. The aim of this study was to assess whether an expanding foam based on hydrophobically modified chitosan (hm-chitosan) may be used as a locally injectable hemostatic agent for the treatment of noncompressible bleeding in a swine model.

METHODS

A closed-cavity, grade V hepato-portal injury was created in all animals resulting in massive noncoagulopathic, noncompressible bleeding. Animals received either fluid resuscitation alone (control, n = 8) or fluid resuscitation plus intraperitoneal hm-chitosan agent through an umbilical port (experimental, n = 18). The experiment was terminated at 180 minutes or death (defined as end-tidal CO <8mmHg or mean arterial pressure [MAP] <15mmHg), whichever came first.

RESULTS

All animals had profound hypotension and experienced a near-arrest from hypovolemic shock (mean MAP = 24 mmHg at 10 minutes). Mean survival time was higher than 150 minutes in the experimental arm versus 27 minutes in the control arm (P < .001). Three-hour survival was 72% in the experimental group and 0% in the control group (P = .002). Hm-chitosan stabilized rising lactate, preventing acute lethal acidosis. MAP improved drastically after deployment of the hm-chitosan and was preserved at 60 mmHg throughout the 3 hours. Postmortem examination was performed in all animals and the hepatoportal injuries were anatomically similar.

CONCLUSION

Intraperitoneal administration of hm-chitosan-based foam for massive, noncompressible abdominal bleeding improves survival in a lethal, closed-cavity swine model. Chronic safety and toxicity studies are required.

摘要

背景

在军事战斗环境中,无法压缩的闭合性体腔失血是潜在可救治死亡的主要原因,而在创伤现场尚无有效的治疗方法。本研究旨在评估基于疏水改性壳聚糖(hm-chitosan)的膨胀泡沫是否可用作一种局部可注射的止血剂,用于治疗猪模型中的不可压缩性出血。

方法

所有动物均创建了闭合性、V 级肝门静脉损伤,导致大量非凝血功能障碍、不可压缩性出血。动物接受单纯液体复苏(对照组,n=8)或通过脐部端口接受液体复苏加腹腔内 hm-chitosan 剂(实验组,n=18)。实验在 180 分钟或死亡(定义为呼气末 CO <8mmHg 或平均动脉压 [MAP] <15mmHg)时终止,以先到者为准。

结果

所有动物均出现严重低血压,并经历因低血容量性休克而近乎停搏(10 分钟时平均 MAP 为 24mmHg)。实验组的平均存活时间长于对照组(150 分钟对 27 分钟,P<.001)。实验组 3 小时存活率为 72%,对照组为 0%(P=.002)。Hm-chitosan 稳定了升高的乳酸,防止了急性致命酸中毒。hm-chitosan 部署后 MAP 明显改善,并在 3 小时内保持在 60mmHg。对所有动物进行了尸体检查,肝门静脉损伤在解剖上相似。

结论

腹腔内给予 hm-chitosan 基泡沫剂治疗大量不可压缩性腹部出血可提高致命性闭合性猪模型的存活率。需要进行慢性安全性和毒性研究。

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