Impact of Blood Storage Duration on Physiologic Measures: RECESS Ancillary Study

描述（由申请人提供）： 红细胞（RBC）输注的预期效果是增加氧气输送，作为保护组织免受缺血的一种手段。然而，存在争议的安全性和有效性输血与红细胞库为短期与长期的存储间隔。虽然一些心脏手术患者的回顾性研究已经证明了RBC储存时间增加与死亡率和发病率增加之间的相关性，但其他研究并未发现任何差异。没有大规模的随机前瞻性人体研究试图将输注RBC的年龄与终末器官功能障碍或死亡的指标相关联。药物研究：REd细胞II储存持续时间研究（RECESS）由NIH资助的输血医学和止血临床试验网络进行。主要目的是确定随机接受储存时间较短（d 10天）与较长（e 21天）的RBC的心脏手术患者（n= 1，612）的结局和死亡率是否存在临床重要差异。RBC储存对与组织氧合和微循环相关的生理变量的影响尚未得到严格研究，也未与临床结局相关。一些研究调查了红细胞输注对组织氧合和微循环的影响。最相关的是一项小型研究，该研究表明随机接受长期储存RBC的创伤患者的组织氧合恶化，但接受短期储存RBC的患者没有变化。拟定的辅助研究：财政限制限制了我们在母试验中研究储存时间对组织氧合和微循环的影响。我们的辅助研究建议在4个研究中心从至少250名RECESS受试者中获得这些额外测量值（例如外周和脑组织氧合和微血管灌注）。具体目标：为了获得最佳组织活力，必须有足够的微循环灌注和红细胞的氧卸载。我们假设，与输注储存较短时间的红细胞相比，输注储存较长时间的红细胞会降低组织氧合和微循环灌注。这项辅助研究将通过测量入组RECESS试验的心脏手术患者输注储存较短或较长时间的RBC后的组织氧合（外周和脑）和微循环灌注来检验这一假设。将在4个时间点获得原始电子数据：手术切口前、ICU RBC输注单元前后即刻和术后24小时。我们将比较两组中这些终点的急性变化（在ICU中给予一个单位RBC之前和之后即刻的变化）以及由累积RBC单位引起的较不急性的变化（从皮肤切开前到术后24小时的变化）。将原始数据发送至哈佛医学院（Boston，MA）经验丰富的核心实验室，并由对研究组分配设盲的个体进行分析。

DESCRIPTION (provided by applicant): The desired impact of red blood cell (RBC) transfusion is to increase oxygen delivery as a means to protect tissues from ischemia. However, controversy exists over the safety and efficacy of transfusion with RBCs banked for short vs. long storage intervals. Although some retrospective studies in cardiac surgery patients have demonstrated associations between increased duration of RBC storage and increased mortality and morbidity, others have not detected any differences. No large, randomized prospective human study has attempted to correlate age of transfused RBCs with measures of end-organ dysfunction or death. PARENT STUDY: The REd CEll Storage Duration Study (RECESS) is being conducted by the NIH funded Transfusion Medicine and Hemostasis Clinical Trials Network. The primary objective is to determine if there are clinically important differences in outcomes and mortality in cardiac surgical patients (n=1,612) randomized to receive RBCs stored for shorter (d 10 days) vs. longer (e 21 days) periods of time. The impact of RBC storage on physiologic variables related to tissue oxygenation and the microcirculation has not been rigorously studied, nor have they been correlated with clinical outcomes. A few studies have investigated the effect of RBC transfusion on tissue oxygenation and the microcirculation. Of most relevance is a small study that demonstrated a deterioration in tissue oxygenation in trauma patients randomized to receive long storage RBCs but no change in those receiving short storage RBCs. PROPOSED ANCILLARY STUDY: Financial constraints limited us from pursuing the impact of storage duration on tissue oxygenation and the microcirculation in the parent trial. Our ancillary study proposes to obtain these additional measurements (e.g. peripheral and cerebral tissue oxygenation, and microvascular perfusion) at 4 study sites from a minimum of 250 participants in RECESS. Specific Aim: For optimal tissue viability, there must be adequate perfusion of the microcirculation and off-loading of oxygen by erythrocytes. We hypothesize that transfusion of RBCs stored for a longer time period decreases tissue oxygenation and microcirculatory perfusion compared with transfusion of RBCs stored for a shorter time period. This ancillary study will test this hypothesis by measuring tissue oxygenation (peripheral and cerebral) and microcirculatory perfusion following the transfusion of RBC that have been stored for shorter or longer periods of time in cardiac surgery patients enrolled in the RECESS trial. Raw electronic data will be obtained at 4 time points: prior to surgical incision, immediately prior to and after the unit of RBC transfusion in the ICU, and at 24 hours postoperatively. We will compare arms with respect to acute changes in these endpoints (change immediately prior to and after the administration of one unit of RBCs in the ICU) as well as less acute changes resulting from cumulative RBC units (change from prior to skin incision to 24 hours postoperatively). Raw data will be sent to an experienced core laboratory at Harvard Medical School, Boston, MA and will be analyzed by individuals blinded to study group assignment.