REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury (RELIEVE-AKI)

摘要 三分之二的急性肾损伤危重患者在开始肾移植时存在液体超负荷。 重症监护室的替代疗法虽然“净超滤（UFNET）”，也被称为净流体 在肾脏替代治疗期间移除，已用于治疗液体超负荷超过 七十年来，UFNET的最佳速率仍然不确定，并发症如低血压和心脏病 心律失常频繁发生，危重病人死亡率超过40%。新出现的证据表明， 观察性研究表明，UFNET率与危重病患者死亡率之间存在“J”形关联。 患有急性肾损伤并接受肾脏替代治疗的患者。UFNET费率较高， 与中等和较低的UFNET率相比，死亡风险增加。了解 UFNET率对结果的因果影响对于设计干预措施以降低死亡率、发展 循证临床实践指南，并实施UFNET的质量措施。如果没有这种 然而，尽管有了知识，但优化UFNET以改善成果仍然是一个问题。因此，我们将进行临床试验， 标题为急性肾损伤患者肾外容量清除率的收缩与自由比较的试验 （RELIEVE-AKI）研究限制性与自由UFNET费率策略的可行性。这项研究是 一项涉及144例急性肾损伤重症患者的阶梯楔形随机分组试验， 在两个医院系统的六个重症监护室进行连续肾脏替代治疗。的 重症监护病房将按1：1随机分配，患者将接受限制性或自由性UFNET 费率策略这两种策略都是护理标准，并且在当前临床实践中常用。在 限制组，将滴定UFNET速率并维持在0.5-1.5 mL/kg/h之间。在自由派中， 将滴定UFNET速率并维持在2.0-5.0 mL/kg/h之间。主要可行性结果为 患者平均UFNET输送率、方案依从性和患者 招聘（目标1）。我们还将探讨替代UFNET费率策略对中学的影响。 结局包括突发事件和心律失常;急救UFNET率的紧急使用 高于分配的治疗组的液体超负荷;肾脏替代治疗的持续时间， 机械通气;重症监护室和住院时间，以及肾独立性 替代治疗和住院死亡率（目标2）。这项实用的临床试验将用于支持 基本原理，评估可行性，并设计一项III期多中心随机试验，以检查 替代UFNET率策略对以患者为中心的临床结局。我们的研究将直接影响 急性肾损伤危重患者的护理，因此将影响临床实践，医生， 政策制定者。

Abstract Two-thirds of critically ill patients with acute kidney injury have a fluid overload at the time of initiation of kidney replacement therapy in the intensive care unit. Although “net ultrafiltration (UFNET),” also known as net fluid removal during kidney replacement therapy, has been used in the treatment of fluid overload for more than seven decades, the optimal rate of UFNET remains uncertain, complications such as hypotension and cardiac arrhythmias occur frequently, and more than 40% of critically ill patients die. Emerging evidence from observational studies suggests a “J” shaped association between UFNET rate and mortality in critically ill patients with acute kidney injury and treated with kidney replacement therapy. Higher UFNET rates are associated with an increased risk of death compared with moderate and lower UFNET rates. Understanding the causal effects of UFNET rate on outcomes is critical to design interventions to reduce mortality, develop evidence-based clinical practice guidelines, and implement quality measures for UFNET. In the absence of such knowledge, optimizing UFNET to improve outcomes will remain problematic. Thus, we will conduct a pilot clinical trial entitled REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury (RELIEVE-AKI) to examine the feasibility of restrictive compared with a liberal UFNET rate strategy. The study is a stepped-wedge cluster-randomized trial involving 144 critically ill patients with acute kidney injury and treated with continuous kidney replacement therapy in six intensive care units across two hospital systems. The intensive care units will be randomized 1:1 in which patients will receive either a restrictive or a liberal UFNET rate strategy. Both strategies are standards of care and are commonly used in current clinical practice. In the restrictive group, the UFNET rate will be titrated and maintained between 0.5-1.5 mL/kg/h. In the liberal group, the UFNET rate will be titrated and maintained between of 2.0-5.0 mL/kg/h. The primary feasibility outcomes are between-group differences in patient mean delivered UFNET rates, protocol adherence, and rate of patient recruitment (Aim 1). We will also explore the effects of alternative UFNET rate strategies on secondary outcomes including hypotensive episodes, and cardiac arrhythmias; emergent use of rescue UFNET rates higher than the assigned treatment arm for fluid overload; duration of kidney replacement therapy and mechanical ventilation; intensive care unit and hospital length of stay, and independence from kidney replacement therapy and hospital mortality (Aim 2). This pragmatic clinical trial will be used to support the rationale, assess feasibility, and design a phase III multicenter randomized trial to examine the effects of alternative UFNET rate strategies on patient-centered clinical outcomes. Our study will have a direct impact on the care of critically ill patients with acute kidney injury and thus will influence clinical practice, physicians, and policymakers.