From the Department of Medicine (K.M., T.N.W.) and Nutrition Research Section (G.F.), Imperial College London, and the Medical Research Council Clinical Trials Unit at University College London (E.C.G., D.M.G., A.S.W.), London, the School of Medicine, Dentistry, and Biomedical Science, Queen's University, Belfast (N.K.), the Liverpool School of Tropical Medicine and Hygiene, Liverpool (I.B.), the Department of Pediatrics, University Hospital of Wales, Cardiff (J.A.E.), and the Centre for Health Economics, University of York, York (P.S.G.) - all in the United Kingdom; Busitema University Faculty of Health Sciences, Mbale Campus, Mbale Regional Referral Hospital (P.O.-O., J.N., C.N.), and the Mbale Blood Transfusion Services (B.W.), Mbale, the Department of Pediatrics, Makerere University and Mulago Hospital (S.K., R.O.O., J.K.), and the Uganda Blood Transfusion Services, National Blood Transfusion Services (D.K.B.), Kampala, and Soroti Regional Referral Hospital, Soroti (F.A., C.E., M.N.) - all in Uganda; the Kenya Medical Research Institute-Wellcome Trust Research Program, Kilifi (K.M., A.M., S.U., T.N.W.); and the College of Medicine and the Malawi-Liverpool-Wellcome Trust Clinical Research Program (G.C., M.M., N.K.) and the Malawi Blood Transfusion Services (B.M.) - all in Blantyre, Malawi.
N Engl J Med. 2019 Aug 1;381(5):420-431. doi: 10.1056/NEJMoa1900100.
Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level.
In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality.
A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days.
Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.).
在撒哈拉以南非洲，严重贫血（血红蛋白水平<6 克/分升）是导致儿童住院和死亡的主要原因。世界卫生组织建议，无论血红蛋白水平如何，对贫血儿童应按每公斤体重输注 20 毫升全血当量进行输血。
在这项两因素、开放性标签试验中，我们随机分配 2 个月至 12 岁、血红蛋白水平<6 克/分升且有严重特征（如呼吸困难或意识降低）的乌干达和马拉维儿童接受 20 毫升/公斤或 30 毫升/公斤的即刻输血。另外三项随机分析研究了即刻输血与不即刻输血、出院后补充微量营养素和出院后用磺胺甲噁唑-甲氧苄啶进行预防。主要结局是 28 天死亡率。
共有 3196 名符合条件的儿童（中位年龄 37 个月；2050 名[64.1%]患有疟疾）被分配接受 30 毫升/公斤（1598 名儿童）或 20 毫升/公斤（1598 名儿童）的输血，并随访 180 天。较高剂量组 1592 名儿童（99.6%）和较低剂量组 1596 名儿童（99.9%）均开始输血（随机分组后平均 1.2 小时）。每名儿童平均（±SD）输注的总血量分别为 475±385 毫升和 353±348 毫升，分别有 197 名儿童（12.3%）和 300 名儿童（18.8%）接受了额外的输血。总体而言，较高剂量组 55 名儿童（3.4%）和较低剂量组 72 名儿童（4.5%）在 28 天内死亡（风险比，0.76；95%置信区间[CI]，0.54 至 1.08；对数秩检验 P=0.12）。这一发现掩盖了根据筛查时是否有发热（>37.5°C）而存在的 28 天死亡率的显著异质性（Sidak 校正后 P=0.001）。在 1943 名（60.8%）无发热的儿童中，30 毫升/公斤的输血量比 20 毫升/公斤的输血量死亡率更低（风险比，0.43；95%CI，0.27 至 0.69）。在 1253 名（39.2%）有发热的儿童中，30 毫升/公斤的输血量比 20 毫升/公斤的输血量死亡率更高（风险比，1.91；95%CI，1.04 至 3.49）。两组随机分组之间在再入院、严重不良事件或 180 天血红蛋白恢复方面均无差异。
两种输血策略的总体死亡率没有差异。（由英国医学研究理事会和国际发展部资助；TRACT 目前的对照试验编号，ISRCTN84086586。）
