Influence of haemodynamic stabilization with crystalloid and colloidal solutions on cerebral perfusion and integrity during haemorrhagic shock in a large animal model

在几种急性或围手术期情况下，可能会发生大量失血导致的出血性休克。因此，生物体不能为其重要器官提供有效的血液和氧气供应，这导致严重的缺血。特别是大脑由于有限的耐受性而迅速遭受缺血，这导致不可逆的损伤。在初始治疗中，可以给予几种晶体或胶体溶液进行液体复苏以恢复微循环。然而，这并不一定保证有效的微循环和器官灌注。最近，欧洲药品管理局对长期使用的标准胶体羟乙基淀粉（HES）进行了负面风险评估，从而加剧了关于液体复苏最有效解决方案的争议性讨论。尽管通过德国S3指南成人血管内容量治疗对HES进行了部分康复，但重点是替代胶体，特别是众所周知的明胶溶液。然而，对于一些迹象，似乎缺乏科学数据。 特别是几种用于治疗出血性休克的液体对脑灌注和完整性的影响是广泛未知的。本研究项目在一项前瞻性随机大动物研究中考察了这些方面。在麻醉的猪中诱导出血性休克，并连续地用不同的液体复苏溶液进行治疗。在液体复苏后12小时内，通过3-Tesla-MR成像和动脉自旋标记技术监测脑灌注。在此期间，前三个小时将没有干预。之后，血流动力学和生理稳定将被期望至基线。为了解释出血性休克的复杂疾病模式，额外的分析集中在血液动力学、凝血功能障碍、内皮完整性、炎症反应和血气参数上。此外，还实时监测外周微循环和氧合。增加了尸检扩展免疫生物学和组织病理学分析。这项研究，这是密切面向临床现实，评估液体复苏的最佳解决方案，有关受损器官灌注再生。

A haemorrhagic shock through massive blood loss may occur in several acute or perioperative scenarios. Consequently, die organism is unable to provide effective blood and oxygen supply for its vital organs, which causes severe ischemia. Especially the brain rapidly suffers from ischemia due to limited tolerance, which causes irreversible damages. In the initial treatment several crystalloid or colloid solutions can be administered for fluid resuscitation to restore the microcirculation. This, however, does not necessarily warrant effective microcirculation and organ perfusion. The controversial discussion regarding the most effective solution for fluid resuscitation was recently intensified through the negative risk assessment for the longtime standard colloid hydroxyethyl starch (HES) by the European Medicines Agency. Despite the partial rehabilitation of HES through the German S3-Guideline Intravascular volume therapy in adults, a focus was set on alternative colloids and particularly the well-known gelatin-based solutions. However, for several indications there seems to be a lack of scientific data. Especially the influence of several fluids for treatment of haemorrhagic shock on the cerebral perfusion and integrity is widely unknown. The present research project examines these aspects in a prospective-randomized large animal study. Haemorrhagic shock is induced in anaesthetized pigs and consecutively treated by different solution for fluid resuscitation. Cerebral perfusion is monitored by means of 3-Tesla-MR imaging and arterial spin labeling technique over twelve hours following fluid resuscitation. During this period there will be no intervention in the first three hours. Afterwards heamodynamic and physiological stabilization will be aspired to baseline. To account for the complex disease pattern of haemorrhagic shock additional analyses focus on haemodynamics, coagulopathy, endothelial integrity, inflammatory response and blood gas parameters. Furthermore, the peripheral microcirculation and oxygenation is monitored in real-time. Post-mortem extended immunobiological and histopathological analyses are added. This study, which is closely oriented on clinical reality, assesses the best possible solution for fluid resuscitation regarding regeneration of the impaired organ perfusion.