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

摘要 2/3的急性肾损伤危重患者在发病时体液过多。 重症监护病房的替代疗法。虽然“净超滤(UFNET)”也被称为净液体 在肾脏摘除替代疗法中，已被用于治疗液体超负荷超过 70年来，UFNET的最佳比率仍然不确定，低血压和心脏等并发症 心律失常频繁发生，40%以上的危重患者死亡。新出现的证据来自 观察性研究表明，危重病患者UFNET发生率和死亡率之间呈“J”型关系 急性肾损伤患者行肾脏替代治疗。更高的UFNET费率是 与中等和较低的UFNET比率相比，死亡风险增加。了解 UFNET比率对预后的因果影响对于设计降低死亡率的干预措施至关重要 循证临床实践指南，并实施UFNET的质量措施。在没有这种情况下 在知识方面，优化UFNET以改善结果仍然是有问题的。因此，我们将进行一项试点临床 急性肾损伤的限制性与自由性体外容量切除评价试验 (RESREASE-AKI)来研究与自由的UFNET利率策略相比，限制的可行性。这项研究是 144例急性肾损伤危重患者的阶梯-楔形整群随机试验 在两个医院系统的六个重症监护病房进行持续的肾脏替代治疗。这个 重症监护病房将以1：1的比例随机进行，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的标准，并在当前的临床实践中普遍使用。在 限制组，UFNET速率将被滴定并维持在0.5-1.5毫升/公斤/小时。在自由组， UFNET速率将被滴定并保持在2.0-5.0毫升/公斤/小时之间。 组间患者平均UFNET交付比率、方案依从性和患者比率的差异 招聘(目标1)。我们还将探讨替代UFNET费率策略对二级市场的影响 结果包括低血压发作和心律失常；紧急使用急救UFNET比率 高于分配的液体超负荷治疗臂；肾脏替代治疗的持续时间和 机械通风；重症监护病房和住院时间，以及独立于肾脏 替代疗法和住院死亡率(目标2)。这项务实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 以患者为中心的临床结果的替代UFNET比率策略。我们的研究将对 对急性肾损伤的危重患者的护理，因此将影响临床实践、医生和 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.