Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Clinics (Sao Paulo). 2009;64(8):803-13. doi: 10.1590/S1807-59322009000800016.
The complications associated with acquiring and storing whole blood for transfusions have launched substantial efforts to develop a blood substitute. The history of these efforts involves a complicated mixture of science, ethics, and business. This review focuses on clinical trials of the three hemoglobin-based oxygen carriers (HBOC) that have progressed to Phase II or III clinical trials: He-mAssist (Baxter; Deerfield, IL, US), PolyHeme (Northfield; Evanston, IL, US), and Hemopure (Biopure; Cambridge, MA, US). Published animal studies and clinical trials carried out in a perioperative setting have demonstrated that these products successfully transport and deliver oxygen, but all may induce hypertension and lead to unexpectedly low cardiac outputs. Overall, these studies suggest that HBOCs resulted in only modest blood saving during and after surgery, no improvement in mortality and an increased incidence of adverse reactions. To date, the results from these perioperative studies have not led to regulatory approval. All three companies instead chose to focus their efforts on large trials of trauma patients in the pre-hospital setting.Baxter abandoned the development of HemAssist after a trial in the U.S. was prematurely halted when the first 100 patients showed significantly increased mortality rates as compared to patients treated with blood products. Northfield's PolyHeme trial demonstrated a non-significant trend towards increased mortality and a very modest reduction in the subsequent need for blood. The testing of Biopure's Hemopure for trauma patients has been halted for several years because of FDA concerns over trial design and study justification. Ethical concerns have also been raised regarding the design and implementation of all HBOC clinical trials.Thus, the available evidence suggests that HemAssist, Polyheme, and Hemopure are associated with a significant level of cardiovascular dysfunction. The next generation of HBOCs remains under development.
与获取和储存全血用于输血相关的并发症促使人们大力开发血液替代品。这些努力的历史涉及到科学、伦理和商业的复杂混合。本综述重点介绍了已进展到 II 期或 III 期临床试验的三种血红蛋白基氧载体 (HBOC) 的临床试验：HemoAssist（百特；美国迪尔菲尔德）、PolyHeme（Northfield；美国埃文斯顿）和 Hemopure（Biopure；美国马萨诸塞州剑桥）。已发表的动物研究和围手术期进行的临床试验表明，这些产品能成功地输送和输送氧气，但所有产品都可能引起高血压，并导致出人意料的低心输出量。总体而言，这些研究表明 HBOC 在手术期间和之后仅能适度节省血液，不能改善死亡率，并增加不良反应的发生率。迄今为止，这些围手术期研究的结果并未导致监管部门批准。这三家公司反而选择将精力集中在创伤患者的院前大试验上。在美国进行的一项试验中，当前 100 名患者的死亡率与接受血液制品治疗的患者相比显著增加时，百特提前停止了 HemoAssist 的开发。Northfield 的 PolyHeme 试验表明，死亡率呈非显著上升趋势，随后对血液的需求也有适度减少。由于 FDA 对试验设计和研究依据的担忧，Biopure 的 Hemopure 用于创伤患者的测试已停止数年。所有 HBOC 临床试验的设计和实施也引发了伦理问题。因此，现有证据表明 HemoAssist、Polyheme 和 Hemopure 与显著水平的心血管功能障碍相关。下一代 HBOC 仍在开发中。
