Brown M S, Keith J F
Department of Pediatrics, Presbyterian/St Luke's Medical Center, Denver, Colorado, USA.
Pediatrics. 1999 Aug;104(2 Pt 1):210-5. doi: 10.1542/peds.104.2.210.
To compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same weekly dose, 500 U/kg, in very low birth weight (VLBW) infants.
Eighty VLBW infants were stratified into two gestational age groups and randomized to receive 500 U/kg of r-EPO either two or five times a week; 72 infants completed at least 4 weeks of study. The primary outcome variable was absolute reticulocyte counts at 4 weeks. Secondary outcome variables were hematocrits, transfusions, iatrogenic blood losses, infections, and serum ferritins. Multiple regression analysis was used to evaluate the secondary outcome variables.
By 4 weeks, absolute reticulocyte counts were higher in the infants given r-EPO five times a week [mean (SEM)]: 173 000/mm(3) (15 000) vs 220 000/mm(3) (18 000), two versus five doses per week, respectively. Hematocrits, 34.9% (0.9) vs 34.1% (0.8), and transfusions per infant, 2.06 (0.4) vs 2.11 (0.4), were not different between the groups. Additionally, 79% of the variance in the amount of blood transfused was accounted for by iatrogenic blood loss, the latter primarily associated with number of days ventilated. Episodes of sepsis and necrotizing enterocolitis were significantly associated with decreased absolute reticulocyte counts and increased transfusions.
More frequent dosing of the same weekly amount of r-EPO produced a significant and sustained increase in stimulated erythropoiesis in VLBW infants. The importance of this finding on reducing transfusions was not able to be demonstrated because this study was not intended to differentiate transfusions. In this population of infants and at the dose level of r-EPO, iatrogenic blood loss contributed more to transfusions than a lower level of erythropoiesis, the former primarily associated with mechanical ventilation. Based on this and other studies, when VLBW infants are at risk for greater phlebotomy losses, it may be justifiable to use more vigorous r-EPO treatment, and when at lower risk to use less frequent dosing to enhance cost-effectiveness.
在极低出生体重（VLBW）婴儿中，比较每周剂量均为500 U/kg的重组人促红细胞生成素（r-EPO）每周给药两次与五次时的促红细胞生成反应。
80名VLBW婴儿被分为两个胎龄组，并随机分为每周接受两次或五次500 U/kg的r-EPO；72名婴儿完成了至少4周的研究。主要结局变量是4周时的绝对网织红细胞计数。次要结局变量包括血细胞比容、输血情况、医源性失血、感染及血清铁蛋白。采用多元回归分析评估次要结局变量。
到4周时，每周接受五次r-EPO的婴儿的绝对网织红细胞计数更高[均值（标准误）]：分别为每周两次与五次给药时，173 000/mm³（15 000）对220 000/mm³（18 000）。两组间的血细胞比容分别为34.9%（0.9）对34.1%（0.8），每名婴儿的输血次数分别为2.06（0.4）对2.11（0.4），均无差异。此外，输血总量79%的变异由医源性失血导致，后者主要与机械通气天数相关。脓毒症和坏死性小肠结肠炎发作与绝对网织红细胞计数降低及输血增加显著相关。
对于VLBW婴儿，相同每周剂量的r-EPO更频繁给药可显著且持续地增加刺激的红细胞生成。由于本研究并非旨在区分输血情况，因此无法证明这一发现对减少输血的重要性。在这群婴儿及r-EPO剂量水平下，医源性失血对输血的影响大于较低水平的红细胞生成，前者主要与机械通气相关。基于本研究及其他研究，当VLBW婴儿有更大的静脉穿刺失血风险时，使用更积极的r-EPO治疗可能是合理的；而当风险较低时，减少给药频率以提高成本效益可能是合理的。
