Martini Judith, Cabrales Pedro, K Ananda, Acharya Seetharama A, Intaglietta Marcos, Tsai Amy G
Department of Bioengineering, University of California, San Diego, Gilman Dr, La Jolla, California 92093, USA.
Crit Care. 2008;12(2):R54. doi: 10.1186/cc6874. Epub 2008 Apr 18.
Preoperative hemodilution is an established practice that is applied to reduce surgical blood loss. It has been proposed that polyethylene glycol (PEG) surface decorated proteins such as PEG-conjugated human serum albumin may be used as non-oxygen-carrying plasma expanders. The purpose of this study was to determine whether there is any difference in survival time after severe hemorrhagic shock following extreme hemodilution using a conventional hydroxyethyl starch (HES)-based plasma expander or PEG-albumin.
Experiments were performed using the hamster skinfold window preparation. Human serum albumin that was surface decorated with PEG was compared with Voluven 6% (Fresenius Kabi, Austria; a starch solution that is of low molecular weight and has a low degree of substitution; HES). These plasma expanders were used for a 50% (blood volume) exchange transfusion to simulate preoperative hemodilution. Exchange transfusion was followed by a 60% (blood volume) hemorrhage to reproduce a severe surgical bleed over a 1 hour period. Observation of the animal was continued for another hour during the shock phase.
The PEG-albumin group exhibited significantly greater survival rate than did the HES group, in which none of the animals survived the hemorrhage phase of the experiment. Among the treatment groups there were no changes in mean arterial pressure and heart rate from baseline after hemodilution. Both groups experienced gradual increases in arterial oxygen tension and disturbance in acid-base balance, but this response was more pronounced in the HES group during the shock period. Mean arterial pressure remained elevated after the initial hemorrhage period in the PEG-albumin group but not in the HES group. Maintenance of a greater mean arterial pressure during the initial stages of hemorrhage is proposed to be in part due to the improved volume expansion with PEG-albumin, as indicated by the significant decrease in systemic hematocrit compared with the HES group. PEG-albumin treatment yielded higher functional capillary density during the initial stages of hemorrhage as compared with HES treatment.
The ability of PEG-albumin to prolong maintenance of microvascular function better than HES is a finding that would be significant in a clinical setting involving preoperative blood management and extreme blood loss.
术前血液稀释是一种既定的做法,用于减少手术失血。有人提出,聚乙二醇(PEG)表面修饰的蛋白质,如PEG偶联的人血清白蛋白,可用作非携氧血浆扩容剂。本研究的目的是确定在使用传统的基于羟乙基淀粉(HES)的血浆扩容剂或PEG白蛋白进行极端血液稀释后,严重失血性休克后的存活时间是否存在差异。
使用仓鼠皮肤褶窗制备进行实验。将表面用PEG修饰的人血清白蛋白与万汶6%(费森尤斯卡比公司,奥地利;一种低分子量、低取代度的淀粉溶液;HES)进行比较。这些血浆扩容剂用于50%(血容量)的换血输血,以模拟术前血液稀释。换血输血后进行60%(血容量)的出血,以重现1小时内严重的手术出血。在休克阶段,对动物再观察1小时。
PEG白蛋白组的存活率显著高于HES组,在HES组中,没有动物在实验的出血阶段存活下来。在各治疗组中,血液稀释后平均动脉压和心率与基线相比没有变化。两组的动脉血氧张力均逐渐升高,酸碱平衡紊乱,但在休克期,HES组的这种反应更为明显。PEG白蛋白组在初始出血期后平均动脉压仍保持升高,而HES组则没有。有人提出,在出血初始阶段维持较高的平均动脉压部分归因于PEG白蛋白改善了容量扩张,与HES组相比,全身血细胞比容显著降低表明了这一点。与HES治疗相比,PEG白蛋白治疗在出血初始阶段产生了更高的功能性毛细血管密度。
PEG白蛋白比HES更好地延长微血管功能维持的能力,这一发现在涉及术前血液管理和大量失血的临床环境中具有重要意义。