Rehm M
Klinik für Anaesthesiologie, Klinikum der Universität München (LMU), Marchioninistr. 15, 81377, München, Deutschland.
Anaesthesist. 2013 Aug;62(8):644-55. doi: 10.1007/s00101-013-2220-8.
Within the framework of a risk assessment procedure the Committee for Risk Assessment of Pharmacovigilance (PRAC) of the European Medicines Agency (EMA) came to the conclusion that the benefits of hydroxylethyl starch infusion solutions (HES) no longer outweighed the risks and on 14 June 2013 recommended that approval should be suspended. Until the procedure has finally been concluded, which could last several months, the Federal Institute for Drugs and Medical Products (BfArM) has recommended that HES should not be used.
The aim of this article is to present the data situation in the most objective and compact way and to ultimately give the reader the foundations in order to be able to form a personal opinion. In addition an attempt will be made to describe a concept how infusion therapy can be carried out without using hydroxyethyl starch (HES).
The background to this decision is given based on a review of the literature and the relevance for intensive care, emergency and perioperative medicine is assessed. Furthermore, a concept of infusion therapy without hydroxyethyl starch is formulated also based on the results of current studies.
For infusion regimens without HES it should be noted that gelatin represents a considerable risk for anaphylactic reactions, that transfer of the new variants of Creutzfeldt-Jacob disease (bovine spongiform encephalopathy BSE) cannot fundamentally be excluded and that some evidence has been found that gelatin can cause kidney injury, probably in a similar way to HES. With respect to the cost-benefit analysis of infusion solutions, blood loss in adults of approximately 1-1.5 l can be substituted by balanced crystalloids (basic therapy 4-5 times compared to the amount of blood lost). For larger blood losses small amounts of hyperoncotic albumin solution (20 %) or alternatively 5 % albumin solution can be used. The 20 % albumin solution seems to have some advantages because it has a higher volume effect (approximately 200 %) and can be more favourable for the fluid balance than 5 % albumin solution. Blood losses greater than 2-3 l normally also require administration of blood products (e.g. fresh frozen plasma FFP and erythrocyte concentrates EC).
The third generation HES solutions cannot be completely replaced by other colloids and in future crystalloids will more strongly again broadly form the basis for infusion therapy. In this aspect balanced crystalloids have priority with respect to the acid-base equilibrium. The history of HES has impressively shown that infusion therapy must be adjusted on a scientifically founded basis, whether in intensive care medicine, perioperative or emergency medicine. Large prospective studies with clinically relevant endpoints are urgently needed.
在风险评估程序的框架内，欧洲药品管理局（EMA）的药物警戒风险评估委员会（PRAC）得出结论，羟乙基淀粉输注溶液（HES）的益处不再大于风险，并于2013年6月14日建议暂停其批准。在该程序最终结束之前（这可能持续数月），德国联邦药品和医疗器械研究所（BfArM）建议不应使用HES。
本文旨在以最客观和简洁的方式呈现数据情况，并最终为读者提供形成个人观点的依据。此外，还将尝试描述一种不使用羟乙基淀粉（HES）进行输液治疗的概念。
基于文献综述给出该决定的背景，并评估其对重症监护、急诊和围手术期医学的相关性。此外，也基于当前研究结果制定了不使用羟乙基淀粉的输液治疗概念。
对于不使用HES的输液方案，应注意明胶存在相当大的过敏反应风险，不能从根本上排除新型克雅氏病（牛海绵状脑病BSE）的传播，并且已发现一些证据表明明胶可能导致肾损伤，其方式可能与HES类似。关于输液溶液的成本效益分析，成人约1 - 1.5升的失血可用平衡晶体液替代（基础治疗量为失血量的4 - 5倍）。对于更大的失血量，可使用少量高渗白蛋白溶液（20%）或5%白蛋白溶液。20%白蛋白溶液似乎具有一些优势，因为它具有更高的扩容效果（约200%），并且在液体平衡方面可能比5%白蛋白溶液更有利。大于2 - 3升的失血通常也需要输注血液制品（如新鲜冰冻血浆FFP和红细胞浓缩液EC）。
第三代HES溶液不能被其他胶体完全替代，未来晶体液将再次更有力地广泛构成输液治疗的基础。在这方面，平衡晶体液在酸碱平衡方面具有优先地位。HES的历史令人印象深刻地表明，无论是在重症监护医学、围手术期还是急诊医学中，输液治疗都必须基于科学依据进行调整。迫切需要开展具有临床相关终点的大型前瞻性研究。
