Department of Emergency Medicine, Brigham and Women's Hospital and Massachusetts General Hospital, 75 Francis Street, Boston, MA 02115, USA.
Resuscitation. 2012 Mar;83(3):285-92. doi: 10.1016/j.resuscitation.2011.09.020. Epub 2011 Oct 5.
Hemorrhagic shock is a pathologic state in which intravascular volume and tissue oxygen delivery are impaired, leading to circulatory collapse and cellular ischemia. Resuscitation with hemoglobin-based oxygen carriers (HBOCs) is appealing in that their use can both restore intravascular volume and tissue oxygenation, without the limitations in supply and immunomodulatory effects of packed red blood cells. However, the development of safe and effective agents has been elusive. In this article, we briefly discuss the major limitations of traditional resuscitative fluids which have driven the continued interest in HBOCs. We then review the history of early HBOC development and the modern understanding of their mechanisms of toxicity, which has informed the rational design of second-generation agents. Finally, we provide an overview of these second-generation HBOCs that are under active investigation or have recently completed phase 3 clinical trials.
失血性休克是一种病理状态，其中血管内容量和组织氧输送受损，导致循环衰竭和细胞缺血。使用血红蛋白基氧载体 (HBOC) 进行复苏很有吸引力，因为它们的使用既可以恢复血管内容量，又可以增加组织氧合，而不会受到红细胞悬液供应限制和免疫调节作用的影响。然而，安全有效的药物的开发一直难以实现。在本文中，我们简要讨论了推动人们对 HBOC 持续关注的传统复苏液的主要限制。然后，我们回顾了早期 HBOC 开发的历史以及对其毒性机制的现代理解，这为第二代药物的合理设计提供了信息。最后，我们概述了正在积极研究或最近完成 3 期临床试验的这些第二代 HBOC。
