Insights from studies of blood substitutes in trauma
Insights from studies of blood substitutes in trauma
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DOI：
10.1097/01.shk.0000180075.76766.fe
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发表时间：
2005-09-01
期刊：
影响因子：
3.1
通讯作者：
Banerjee, A
中科院分区：
文献类型：
--
作者：
Moore, EE;Johnson, JL;Banerjee, A
大多数权威机构认为，对血液替代品的最大需求是在意外急性失血的患者中，而创伤是最有可能的情况。今天达到高级临床试验的血液替代品是从血红蛋白中提取的红细胞(RBC)替代品。目前在FDA第三阶段临床试验中测试的基于血红蛋白的氧气载体(HBOC)是聚合血红蛋白溶液。在失血性休克中恢复氧输送的标准方法是用晶体注射以扩大血管内容量，然后储存红细胞以治疗严重贫血。然而，同种异体红细胞可能具有不利的免疫炎症效应，从而增加损伤后多器官衰竭(MOF)的风险。第二阶段临床试验，以及体外和体内的研究表明，用HBOC代替储存的红细胞复苏可以减轻MOF发病机制中的全身炎症反应。具体地说，HBOC已被证明可以避免储存的RBC引发的中性粒细胞启动、内皮激活和白细胞介素6、8和10的系统性释放。基于这一背景和其他人的工作，我们启动了一项多中心院前试验，在该试验中，严重创伤患者大量失血(全身血压
Most authorities believe that the greatest need for blood substitutes is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes, derived from hemoglobin. The hemoglobin-based oxygen carriers (HBOCs) tested currently in FDA Phase III clinical trials are polymerized hemoglobin solutions. The standard approach to restoring oxygen delivery in hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. However, allogenic RBCs may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with a HBOC-in lieu of stored RBCs-attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, an HBOC has been shown to obviate stored RBC provoked neutrophil priming, endothelial activation, and systemic release of interleukins 6, 8, and 10. Based on this background and work by others, we have initiated a multicenter prehospital trial in which severely injured patients with major blood loss (systemic blood pressure