A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients with Acute Heart Failure

摘要 在100万急诊科(ED)因急性心力衰竭(AHF)住院的患者中，LOOP 利尿剂是超过80%的时间里唯一使用的静脉注射疗法，尽管只有C级证据。 研究的重点是静脉注射利尿剂的初始剂量，但未能找到一种最有效的策略。 利尿剂的剂量和反应差异很大，导致许多患者得不到充分的治疗。有些人有一个临床 对利尿剂治疗的反应导致症状改善并在3-5天内出院 几天。然而，尽管症状明显改善，这些患者中有50%没有体重减轻和 多达50%的患者带着残留的拥堵离开了医院。残留充血和体重最轻的患者 在出院时的损失经历了不成比例的高再入院人数。高达20%的 住院患者对静脉环状利尿剂的初始反应较差，被认为是利尿剂“非利尿剂”。 具有响应性“。由于未经处理的液体和钠的滞留，会发生恶化的心力衰竭(WHF) 在他们住院期间经常发生。发生WHF的患者住院时间较长 (LOS)，死亡率增加，并消耗明显更多的资源。有一种尚未得到满足的个性化需求 利尿治疗，以改善缓解充血，并随后减少不良事件。然而，即使知道 充血在AHF中的基础作用，临床医生对如何优化 利尿剂反应性。尽管多项临床试验旨在阐明环状利尿剂的理想方法 拥堵的管理，剂量和路线的适当选择，以及确定 利尿剂治疗的有效性在很大程度上仍处于经验阶段。标准化的、协议驱动的治疗路径 对于住院患者开始的前两个小时的急救评估和采用客观措施 需要利尿剂反应。这将最大限度地提高利尿剂的效率，有助于更快地解决充血， 避免WHF和长时间的LOS，减少AHF的再入院。我们强劲的初步数据表明 尿钠预测门诊和住院患者首次利尿剂剂量后的住院时间和结果 设置，并可用于滴定利尿剂。点尿钠滴定环状利尿剂的初步应用 AHF住院患者的剂量和最大反应显示出令人信服的改善充血和 减肥。我们建议在急诊室开始这一方案，并假设它将改善AHF的预后。 到结构化的以指导方针为基础的日常护理。具体地说，我们假设使用现场尿液引导的利尿剂治疗。 将：1)与基于结构化指南的指南相比，在5天内导致全球临床状况显著改善 常规护理，2)在5天内显著改善拥堵，在30天内显著改善全球排名 相对于结构化的、基于指南的日常护理。急性心力衰竭患者的早期程序化治疗将更多 迅速改善呼吸困难，避免院内WHF的发展，使医院的充血得到更大的缓解 出院，从而防止心力衰竭相关的再入院和心血管死亡。

Abstract Of the one million emergency department (ED) patients hospitalized with acute heart failure (AHF), loop diuretics are the only IV treatment used over 80% of the time, although only with level of evidence C. Prior studies have focused on the initial dose of IV diuretic and failed to find one strategy with maximal efficacy. Diuretic dosing and response vary widely, leaving many patients inadequately treated. Some have a clinical response to diuretic therapy resulting in symptom improvement and discharge from the hospital within 3-5 days. However, despite apparent symptom improvement, 50% of these patients experience no weight loss and up to 50% leave the hospital with residual congestion. Patients with residual congestion and minimal weight loss at hospital discharge experience a disproportionately high number of readmissions. Up to 20% of hospitalized patients have a poor initial response to IV loop diuretics, and are considered diuretic “non- responsive”. As a result of untreated fluid and sodium retention, worsening heart failure (WHF) occurs frequently during their inpatient stay. Patients who develop WHF experience prolonged hospital lengths of stay (LOS), increased mortality, and consume significantly more resources. There is an unmet need to individualize diuretic therapy to improve decongestion and subsequently reduce adverse events. Yet, even knowing the fundamental role of congestion in AHF, there is little consensus among clinicians about how to optimize diuretic responsiveness. Despite multiple clinical trials aiming to clarify the ideal approach to loop diuretics in the management of congestion, the appropriate selection of dose and route, as well as determination of effectiveness of diuretic therapy remains largely empirical. A standardized, protocol-driven treatment pathway for hospitalized patients started in the first two hours of ED evaluation and utilizing objective measures of diuretic response is needed. This would maximize diuretic efficiency, facilitate quicker resolution of congestion, avoid WHF and prolonged LOS, and reduce AHF readmissions. Our strong preliminary data suggests low urine sodium predicts length of stay and outcomes after initial diuretic dosing in the outpatient and inpatient setting, and can be used to titrate diuretics. Our preliminary use of spot urine sodium to titrate loop diuretic doses and maximize response in inpatients with AHF has shown compelling improvements in congestion and weight loss. We propose to begin this protocol in the ED and hypothesize it will improve AHF outcomes relative to structured guideline-based usual care. Specifically, we hypothesize use of spot urine guided diuretic therapy will: 1) result in significant improvement in global clinical status at 5 days relative to structured guideline-based usual care, and 2) result in significant improvement in congestion at 5 days and in global rank at 30 days relative to structured guideline-based usual care. Early protocolized treatment of patients with AHF will more rapidly improve dyspnea, avoid development of in-hospital WHF, result in greater decongestion at hospital discharge, and therefore prevent HF-related readmissions and CV death.