Randomized trials using point of care-guided manipulation of dialysate potassium, dialysate bicarbonate, and ultrafiltration rate to prevent hemodilaysis-associated arrythmia

透析清除液体、钾和酸对依赖血液透析(HD)的人来说是挽救生命的 肾脏疾病的阶段。然而，有令人信服的证据表明，透析程序会增加这种风险。 严重心律失常，包括心脏骤停(SCA)--约占#年所有死亡人数的25% HD患者，其发病率是普通人群的20倍--以及心房颤动(AF)--高度 HD的流行状况与心血管发病率、死亡率和中风密切相关。具体来说， 有强烈和一致的观察将透析液超滤率(UF)和血清联系起来 以及透析液中钾和碳酸氢盐浓度对致命性和非致命性心律失常的影响。考虑到高利率 HD患者的心血管发病率和死亡率以及标准心血管疾病的证据 治疗是无效的，设计了前瞻性随机试验来调查目前的变化 关于透析处方的可修改方面的治疗范例将降低心律失常的风险 事件代表了一种新的方法，具有极大的降低死亡率的潜力。从历史上看，这种研究 由于长期心电监测的限制，一直是不可行的，但新技术已经 克服这一挑战：我们独特的高清植入式循环录音(ILR)技术体验 患者，以及我们在以患者为中心的HD研究方面的专业知识使我们处于进行 利用ILR技术进行护理点(POC)电解液测试的随机交叉试验 比较透析处方的3种随机操作对心律失常的长期影响：低与低。 血清到透析液的钾梯度高，血清-透析液的碳酸氢盐梯度低与高，以及低与。 高超滤率(UF)。我们提议的试验将改变对透析处方的理解 影响HD相关性心律失常，并将直接影响临床护理。当前应用程序寻求支持 根据R34机制进行中试试验，旨在：测试POC引导的透析液的可行性 钾和碳酸氢盐处方以及限制HD试验中UF比率的可行性(目标1)； 分析ILR置入术与POC引导相结合监测心律失常试验的招募可行性 碳酸氢盐或钾盐处方或超滤率操纵(目标2)；并改进变化的效果估计 每次干预的心律失常频率(目标3)。这些研究将提供关于因果关系的独特数据。 透析在HD相关性心律失常中的作用以及设计明确的、大的、 扩大有可能改变透析的介入试验。

Dialytic removal of fluid, potassium and acid is life-saving in individuals with hemodialysis (HD)-dependent end stage renal disease. However, there is compelling evidence that the dialysis procedure contributes to the risk of serious arrhythmias including sudden cardiac arrest (SCA)—which accounts for roughly 25% of all deaths in HD patients and occurs at a rate 20x that in the general population—and atrial fibrillation (AF)—a highly prevalent condition in HD strongly associated with cardiovascular morbidity, mortality and stroke. Specifically, there are strong and consistent observations linking the dialytic fluid ultrafiltration (UF) rate as well as serum and dialysate potassium and bicarbonate concentrations to fatal and non-fatal arrhythmia. Given the high rates of cardiovascular morbidity and mortality in HD patients and the evidence that standard cardiovascular therapies are ineffective, designing prospective, randomized trials to investigate whether changes to current treatment paradigms regarding modifiable facets of the dialysis prescription will reduce the risk of arrhythmic events represents a novel approach with the strong potential to reduce mortality. Historically, such studies have been unfeasible due to the limits of long-term electrocardiographic monitoring, but new technologies have overcome this challenge: Our unique experience with novel implantable loop recording (ILR) technology in HD patients, and our expertise in HD patient-oriented studies place us in the optimal position to conduct randomized, crossover trials leveraging point of care (POC) electrolyte testing with ILR technology in order to compare the long-term impact of 3 randomized manipulations of the dialysis prescription on arrhythmia: low vs. high serum to dialysate potassium gradient, low vs. high serum-dialysate bicarbonate gradient, and low vs. high ultrafiltration (UF) rates. Our proposed trials will transform understanding of how dialysis prescriptions impact HD-associated arrhythmia and will directly influence clinical care. The current application seeks support under the R34 mechanism to conduct pilot trials designed to: Test the feasibility of POC-guided dialysate potassium and bicarbonate prescriptions as well as the feasibility of limiting UF rate in an HD trial (Aim 1); Analyze recruitment feasibility for trials combining ILR insertion to monitor arrhythmia with POC-guided bicarbonate or potassium prescriptions or UF rate manipulation (Aim 2); and Refine effect estimates for change in arrhythmia frequency with each intervention (Aim 3). These studies will provide unique data on the causal role of dialysis in HD-associated arrhythmia and the information necessary for the design of definitive, large- scale interventional trials with the potential to transform dialysis.