Treib J, Baron J F, Grauer M T, Strauss R G
Department of Neurology, University Hospital of the Saarland, Homburg, Germany.
Intensive Care Med. 1999 Mar;25(3):258-68. doi: 10.1007/s001340050833.
Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.
羟乙基淀粉（HES）是最常用的血浆代用品之一。全球存在多种不同的HES溶液，其药理特性差异很大。HES根据其生产的或体外分子量（MW）分为高分子量（450 - 480 kDa）、中分子量（200 kDa）和低分子量（70 kDa）淀粉制剂。然而，这并不充分，因为HES在体内代谢时，其分子量会发生变化，而正是体内分子量决定了每种HES的治疗作用和不良反应。代谢速率主要取决于羟乙基取代程度（范围为0.4至0.7）以及羟乙基化的C2/C6比率。高取代度和高C2/C6比率会导致HES代谢缓慢，从而在体内产生较大的分子量。缓慢降解的高分子量HES 450/0.7和中分子量HES 200/0.62具有较高的体内分子量，通过肾脏缓慢清除。因此，这些淀粉具有相对持久的容量效应。当输注较高体积（>1500 ml）时，大分子会在血浆中蓄积。这可能由于因子VIII/血管性血友病因子降低、血小板功能缺陷、掺入纤维蛋白凝块以及对流变学参数产生不利影响而导致出血并发症。快速降解的中分子量HES 200/0.5或低分子量HES 70/0.5在体内迅速分解为更小、更有利的分子大小，导致肾脏清除更快、容量效应更短，并且对凝血和流变学参数的不良反应更少。出于历史和市场原因，在美国仅可获得缓慢降解的高分子量HES（480/0.7）。在欧洲，有多种HES溶液可供选择，以中分子量、易于降解的HES（200/0.5）为主。由于国际竞争加剧以及新开发淀粉的可得性，了解HES的药理特性以及各个制剂的优缺点非常重要。
