Suttner S, Boldt J
Klinik für Anästhesie und Operative Intensivmedizin, Klinikum der Stadt Ludwigshafen.
Anasthesiol Intensivmed Notfallmed Schmerzther. 2004 Feb;39(2):71-7. doi: 10.1055/s-2004-817674.
Hydroxyethyl starch (HES) solutions are synthetic colloids with the pharmacological properties that are closest to natural colloids. In Germany, numerous types of HES preparations with different combinations of concentration, weight-averaged mean molecular weight (Mw), and hydroxyethylation pattern are available. They differ with regard to their volume-supporting capacity, intravascular half-life, and side effect profile. The elimination of HES molecules varies with the Mw and degree of substitution (DS). Large HES molecules undergo hydrolytic cleavage by alpha-amylase and are excreted in the urine, or they are phagocytosed by the reticuloendothelial system. The smaller HES molecules are eliminated by glomerular filtration. The higher the DS, the slower the metabolism and elimination of the molecule. Although HES can be used safely even in large doses in patients without altered kidney function, renal dysfunction and acute renal failure after HES infusion have been reported in patients who share several risk factors, such as preexisting renal disease, advanced age in combination with dehydration, or treatment with high doses of slow degradable HES solutions. Since there is no direct chemical toxicity of HES, the most likely mechanism for HES-induced renal dysfunction may be swelling and vacuolization of tubular cells ("osmotic nephrosis-like lesions") and tubular obstruction due to the production of hyperviscous urine. Considering this pathogenesis, it can be hypothesized that all hyperoncotic colloid solutions can induce renal impairment. In the case of HES, the risk of high plasma colloid osmotic pressure and thus the risk of acute renal failure are probably increased by high concentrations of the colloid or repeated administration of slowly degradable HES with a high Mw and DS. With adequate hydration, using sufficient amounts of crystalloids, HES has little if any adverse effects on renal function. Furthermore, modern -rapidly degradable HES solutions with a low Mw and DS, such as HES 130/0.4, do not increase the risk for renal dysfunction even when used in large amounts perioperatively.
羟乙基淀粉(HES)溶液是具有最接近天然胶体药理学特性的合成胶体。在德国,有多种不同浓度、重均平均分子量(Mw)和羟乙基化模式组合的HES制剂可供使用。它们在容量支持能力、血管内半衰期和副作用方面存在差异。HES分子的清除随Mw和取代度(DS)而变化。大的HES分子通过α-淀粉酶进行水解裂解并经尿液排出,或者被网状内皮系统吞噬。较小的HES分子通过肾小球滤过清除。DS越高,分子的代谢和清除越慢。尽管在肾功能未改变的患者中即使大剂量使用HES也可安全使用,但在有多种危险因素的患者中,如存在肾脏疾病、高龄合并脱水或使用高剂量缓慢降解的HES溶液进行治疗,已有HES输注后出现肾功能障碍和急性肾衰竭的报道。由于HES没有直接的化学毒性,HES诱导肾功能障碍最可能的机制可能是肾小管细胞肿胀和空泡化(“渗透性肾病样病变”)以及由于产生高粘滞性尿液导致的肾小管阻塞。考虑到这种发病机制,可以推测所有高渗胶体溶液都可诱发肾损伤。就HES而言,高血浆胶体渗透压的风险以及因此急性肾衰竭的风险可能因胶体高浓度或反复给予高Mw和DS的缓慢降解HES而增加。通过充分补液,使用足够量的晶体液,HES对肾功能几乎没有不良影响。此外,现代的低Mw和DS的快速降解HES溶液,如HES 130/0.4,即使在围手术期大量使用也不会增加肾功能障碍的风险。