Ogden J E, Parry E S
Chemical and Biological Defense Establishment, Salisbury, Wiltshire, United Kingdom.
Int Anesthesiol Clin. 1995 Winter;33(1):115-29.
It is clear from the trials described here that the number of different products being tested and the potential variation between batches of the same product present major problems in evaluating the safety and efficacy of hemoglobin-based oxygen carriers. The recent CBER "Points to Consider" document [42] makes clear that an understanding of the safety of oxygen carriers in humans is of paramount importance. In the event of phase II or indeed phase III trials being approved, the need may still remain for additional phase I or preclinical studies, particularly as unwanted or toxic properties of the solutions affect efficacy. It is likely that demonstrating safety and efficacy in acute hemorrhagic shock will be the most difficult task, as this is a complex clinical indication and is often accompanied by multisystem damage. The use of a hemoglobin-based oxygen carrier in this setting must have a distinct advantage over a plasma expander alone. In the application of perioperative transfusion, a decreased requirement for red cell transfusion has already been accepted as a basis for the efficacy for erythropoietin. However, in the case of a hemoglobin-based oxygen carrier, the reduction of red cell requirement in perioperative procedures would need to be balanced against any adverse drug reactions or unacceptable hemodynamic effects that may be caused by the product. It appears that there are still numerous hurdles to overcome in the development of hemoglobin-based red cell substitutes. Before these products can become established in medical practice, it is imperative that the potential mechanisms of toxicity of cell-free hemoglobin are clearly understood. Approval of hemoglobin-based oxygen carriers for clinical use will depend not only on clear demonstration of both safety and efficacy but also on risk-versus-benefit issues. Our understanding of the physiological effects of these products will evolve as progress is made in their clinical evaluation.
从这里描述的试验可以清楚地看出，正在测试的不同产品的数量以及同一产品不同批次之间的潜在差异，在评估基于血红蛋白的氧载体的安全性和有效性方面存在重大问题。美国生物制品评估和研究中心（CBER）最近的“考虑要点”文件[42]明确指出，了解氧载体在人体中的安全性至关重要。如果二期试验甚至三期试验获得批准，可能仍需要进行额外的一期试验或临床前研究，特别是当溶液的不良或毒性特性影响疗效时。在急性失血性休克中证明安全性和有效性可能是最困难的任务，因为这是一个复杂的临床指征，并且常常伴有多系统损伤。在这种情况下使用基于血红蛋白的氧载体必须比单独使用血浆扩容剂具有明显优势。在围手术期输血的应用中，减少红细胞输血的需求已被公认为促红细胞生成素疗效的基础。然而，对于基于血红蛋白的氧载体，围手术期程序中红细胞需求的减少需要与该产品可能引起的任何药物不良反应或不可接受的血流动力学效应相平衡。在基于血红蛋白的红细胞替代物的开发中似乎仍有许多障碍需要克服。在这些产品能够在医学实践中确立之前，必须清楚地了解无细胞血红蛋白潜在的毒性机制。基于血红蛋白的氧载体临床使用的批准不仅将取决于安全性和有效性的明确证明，还将取决于风险与效益问题。随着这些产品临床评估的进展，我们对其生理效应的理解将会不断发展。
