Schick Martin Alexander, Baar Wolfgang, Bruno Raphael Romano, Wollborn Jakob, Held Christopher, Schneider Reinhard, Flemming Sven, Schlegel Nicolas, Roewer Norbert, Neuhaus Winfried, Wunder Christian
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany.
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
PLoS One. 2015 Sep 4;10(9):e0137247. doi: 10.1371/journal.pone.0137247. eCollection 2015.
Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6 h. After 24 h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1-4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion.
容量治疗是围手术期日常护理中的标准程序,关于使用羟乙基淀粉(HES)进行胶体复苏的益处,目前仍在讨论中。在脓毒症中,由于急性肾损伤(AKI)风险较高,应避免使用HES。在非脓毒症患者中使用HES的结果存在争议。因此,我们进行了一项动物研究,以评估6% HES 130/0.4在脓毒症或健康条件下对肾脏完整性的影响。脓毒症通过标准化的升结肠支架腹膜炎(sCASP)诱导。sCASP组和对照组(C)在24小时内未接受治疗。18小时后,sCASP+HES组(sCASP+VOL)和对照组+HES(C+VOL)在6小时内接受50 ml/kg平衡的6% HES(VOL)130/0.4。24小时后,通过对再次麻醉的大鼠进行菊粉和对氨基马尿酸清除率测量肾功能,并分析血清尿素、肌酐(crea)、胱抑素C和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)以及组织病理学。体外培养人近端肾小管细胞(PTC),加入或不加入脂多糖(LPS),并加入0.1 - 4.0% VOL。用XTT法测量细胞活力,用LDH试验测量细胞毒性。sCASP诱导严重的脓毒症性AKI,通过关注VOL的清除率或肌酐测量,在肾功能方面显示出不同的结果。仅使用HES(C+VOL)在无sCASP的情况下会使肾功能恶化。组织病理学显示,与对照组相比,所有HES组均有明显紊乱。在体外,LPS并未加重HES诱导的PTC细胞活力降低。我们首次证明,在体内6小时内应用50 ml/kg 6% HES 130/0.4可诱导无炎症的AKI。sCASP诱导的脓毒症性AKI的严重程度可能不再受容量扩张方式的影响。