Departments of Cardiothoracic Anesthesiology and Outcomes Research, Cleveland Clinic, Cleveland, OH, USA.
Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA.
Anaesthesia. 2020 Sep;75(9):1180-1190. doi: 10.1111/anae.14994. Epub 2020 Feb 18.
Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase-associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin-18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non-inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase-associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1-68 [0-996]) ng.ml ) vs. albumin (5 (2-74 [0-1604]) ng.ml ), although not non-inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin-18 concentrations were reduced, but interleukin-18 and kidney injury were again not non-inferior. Of 11 individual coagulation measures, platelet count and function, nine were non-inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid-induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non-inferiority. Long-term mortality and kidney function appeared similar between starch and albumin.
在接受心脏手术的患者中，第三代羟乙基淀粉溶液是否会引起肾脏损伤或止血异常仍不清楚。我们检验了以下假设：与人体白蛋白 5%相比，术中给予第三代淀粉不会加重心脏手术患者的术后肾功能或止血异常。这是一项三盲、非劣效性临床试验，随机分配接受择期主动脉瓣置换术（伴或不伴冠状动脉旁路移植术）的 40-85 岁患者，用 6%淀粉 130/0.4 或 5%人体白蛋白进行血浆容量替代。我们的主要结局是术后尿中性粒细胞明胶酶相关脂质运载蛋白浓度，这是术后肾损伤的敏感和早期标志物。其次，我们评估了尿白介素-18；根据肌酐 RIFLE 标准评估急性肾损伤，评估凝血措施、血小板计数和功能。采用多重比较校正评估非劣效性（差值 15%）。我们按计划纳入了 141 名患者（69 名淀粉组，72 名白蛋白组）。主要分析结果表明，羟乙基淀粉组术后尿中性粒细胞明胶酶相关脂质运载蛋白（中位数（IQR[范围]））为 5（1-68[0-996]）ng.ml）略低于白蛋白组（5（2-74[0-1604]）ng.ml），尽管由于预期外的变异性较高，不具有非劣效性[几何均数比（95%CI）0.91（0.57，1.44）；p=0.15]。尿白介素-18 浓度降低，但白介素-18 和肾损伤仍不具有非劣效性。在 11 项单独的凝血措施中，血小板计数和功能有 9 项与白蛋白不具有非劣效性。另外两项，血栓弹力图 R 值和花生四烯酸诱导的血小板聚集，临床相似，但置信区间较宽。心脏手术期间给予淀粉与白蛋白相比，对术后肾功能、凝血、血小板计数和血小板功能的观察结果相似，但由于预期外的变异性和宽置信区间，无法得出非劣效性的结论。淀粉组和白蛋白组的长期死亡率和肾功能似乎相似。
