From the Departments of Medicine (N.M.H., D.M.A., Y.L., R.B., M.A.C., P.J.D., J.H., T.E.W., J.W.E.), Pathology and Molecular Medicine (N.M.H., M.A.C., T.E.W., K.E.W.), and Clinical Epidemiology and Biostatistics (N.M.H., P.J.D.) and McMaster Centre for Transfusion Research (N.M.H., R.J.C., D.M.A., Y.L., R.B., T.E.W., K.E.W.), McMaster University, Canadian Blood Services (N.M.H., D.M.A., K.E.W.), the Population Health Research Institute (P.J.D., J.W.E.), and the Thrombosis and Atherosclerosis Research Institute (J.W.E.), Hamilton, ON, and the Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON (R.J.C.) - all in Canada; SA Pathology Transfusion Service, Flinders Medical Centre and Flinders University, Adelaide, SA, Australia (D.R., M.S.-T.); the Departments of General Anesthesiology (A.K.) and Outcomes Research (A.K., D.I.S.), Anesthesiology Institute, and the Robert J. Tomsich Pathology and Laboratory Medicine Institute and the Department of Laboratory Medicine (P.F.), Cleveland Clinic, Cleveland; and Meir Medical Center Kfar Saba and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (M.E.).
N Engl J Med. 2016 Nov 17;375(20):1937-1945. doi: 10.1056/NEJMoa1609014. Epub 2016 Oct 24.
Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients.
In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio. Only patients with type A or O blood were included in the primary analysis, since pilot data suggested that our goal of achieving a difference in the mean duration of blood storage of at least 10 days would not be possible with other blood types. Written informed consent was waived because all the patients received treatment consistent with the current standard of care. The primary outcome was in-hospital mortality, which was estimated by means of a logistic-regression model after adjustment for study center and patient blood type.
From April 2012 through October 2015, a total of 31,497 patients underwent randomization. Of these patients, 6761 who did not meet all the enrollment criteria were excluded after randomization. The primary analysis included 20,858 patients with type A or O blood. Of these patients, 6936 were assigned to the short-term storage group and 13,922 to the long-term storage group. The mean storage duration was 13.0 days in the short-term storage group and 23.6 days in the long-term storage group. There were 634 deaths (9.1%) in the short-term storage group and 1213 (8.7%) in the long-term storage group (odds ratio, 1.05; 95% confidence interval [CI], 0.95 to 1.16; P=0.34). When the analysis was expanded to include the 24,736 patients with any blood type, the results were similar, with rates of death of 9.1% and 8.8%, respectively (odds ratio, 1.04; 95% CI, 0.95 to 1.14; P=0.38). Additional results were consistent in three prespecified high-risk subgroups (patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer).
Among patients in a general hospital population, there was no significant difference in the rate of death among those who underwent transfusion with the freshest available blood and those who underwent transfusion according to the standard practice of transfusing the oldest available blood. (Funded by the Canadian Institutes of Health Research and others; INFORM Current Controlled Trials number, ISRCTN08118744 .).
随机对照试验表明，长时间储存后的输血并不会增加患者发生不良结局的风险，但这些试验大多局限于高危人群，且没有足够的效力来检测死亡率方面微小但有临床意义的差异。我们试图在住院患者的一般人群中，确定血液储存时间对输血后死亡率的影响。
在这项在四个国家的六家医院开展的实用型、随机、对照试验中，我们以 1:2 的比例将需要红细胞输血的患者随机分为接受储存时间最短（短期储存组）或最长（长期储存组）的血液。仅纳入 A 型或 O 型血的患者进行主要分析，因为初步数据表明，我们实现血液储存时间平均差异至少 10 天的目标对于其他血型是不可能的。由于所有患者都接受了符合当前护理标准的治疗，因此免除了书面知情同意。主要结局是院内死亡率，采用 logistic 回归模型在调整研究中心和患者血型后进行估计。
2012 年 4 月至 2015 年 10 月，共有 31497 名患者接受了随机分组。其中，6761 名患者在随机分组后因不符合所有入组标准而被排除。主要分析包括 20858 名 A 型或 O 型血的患者。其中，6936 名患者被分配到短期储存组，13922 名患者被分配到长期储存组。短期储存组的平均储存时间为 13.0 天，长期储存组为 23.6 天。短期储存组有 634 例死亡（9.1%），长期储存组有 1213 例（8.7%）（比值比，1.05；95%置信区间[CI]，0.95 至 1.16；P=0.34）。当分析扩展到包括任何血型的 24736 名患者时，结果相似，死亡率分别为 9.1%和 8.8%（比值比，1.04；95%CI，0.95 至 1.14；P=0.38）。在三个预先指定的高危亚组（接受心血管手术的患者、入住重症监护病房的患者和患有癌症的患者）中，额外的结果也是一致的。
在综合医院的患者中，输注最新鲜的可用血液的患者与根据输注最陈旧的可用血液的标准做法进行输血的患者之间，死亡率无显著差异。（由加拿大卫生研究院和其他机构资助；INFORM 现况对照试验编号，ISRCTN08118744。）
