A Randomized Controlled Multicenter Trial on Albumin Replacement In Septic Shock (ARISS)

白蛋白是细胞外空间内液体分布的关键调节因子，除了具有致癌活性外，还具有多种性质，包括结合和运输几种内源性分子，抗炎和抗氧化作用，一氧化氮调节和缓冲功能。越来越多的证据表明，补充白蛋白可能只在创伤严重时才能提供生存优势，如感染性休克患者。对于这些感染性休克患者白蛋白替代治疗可能产生的影响，缺乏前瞻性随机试验。本研究的目的是探讨与无白蛋白的复苏和容量维持相比，用白蛋白替代并将血清白蛋白水平维持在30g/L以上28天是否能提高感染性休克患者的存活率。在这项前瞻性、多中心、随机试验中，感染性休克的成年患者(~18岁)将在获得治疗或对照组知情同意后，在感染性休克发病后最多24小时内随机分配。分配到治疗组的患者将在2-3小时内接受60克负荷量20%的人白蛋白。在随机使用40-80克20%人白蛋白输液后，ICU中的血清白蛋白水平将维持在30克/L以上最长28天。对照组按常规治疗，在感染性休克的复苏和维持期首选晶体。主要终点是90天死亡率，次要终点包括28天、60天、ICU和住院死亡率、器官功能障碍/衰竭，以及ICU和住院时间。总共需要分析1412名患者，每组706名。假设辍学率为15%，总共需要分配1662名患者。这项研究有望影响感染性休克患者的日常临床实践，并将对感染性休克患者的治疗指南产生直接影响。

Albumin is a key regulator of fluid distribution within the extracellular space and posses several properties beyond its oncotic activity, including binding and transport of several endogenous molecules, anti-inflammatory and anti-oxidant actions, nitric oxide modulation, and buffer function. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. Prospective randomized trials on the possible impact of albumin replacement in these patients with septic shock are lacking. The aim of the proposed study is to investigate whether the replacement with albumin and the maintenance of its serum levels above 30 g/L for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. In this prospective, multicenter, randomised trial, adult patients (~18 yr) with septic shock will be randomly assigned within a maximum of 24 hours after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group will receive a 60 gm loading dose of human albumin 20% over 2-3 hours. Serum albumin levels will be maintained above 30 gm/L in the ICU for a maximum of 28 days following randomization using 40-80 gm human albumin 20% infusion. The control group will be treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary end point is 90 days mortality and secondary end points include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, and length of ICU and hospital stay. In total 1412 patients need tobe analyzed, 706 per group. Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated. The study is expected to influence the every-day clinical practice and will have a direct impact an the guidelines of treating patients with septic shock.