重组人促红细胞生成素在早产儿脑损伤治疗中的安全剂量分析

Safe dose analysis of recombinant human erythropoietin in the treatment of brain injury in premature infants

目的分析重组人促红细胞生成素在早产儿脑损伤治疗中的安全剂量。方法选取121例2017年1月~2018年10月于哈尔滨医科大学附属第二医院妇产科分娩的缺血性脑损伤早产儿为回顾性研究对象,分为未应用重组人促红细胞生成素治疗组(简称:未用组,24例)和0.2倍、0.4倍、0.6倍、0.8倍重组人促红细胞生成素说明书参考剂量(750 U/kg·d)组(分别简称为:0.2倍组、0.4倍组、0.6倍组、0.8倍组,病例数分别为26例、31例、22例、18例)。分析不同剂量组的神经功能指标、40周龄神经功能、炎性因子及不良反应变化情况。结果血清神经功能(DP、EP、NSE)和炎性相关因子(IL-6、TNF-α、hs-CRP)比较:未用组、0.2倍组、0.4倍组、0.6倍组、0.8倍组依次降低,未用组、0.2倍组、0.4倍组与前一剂量组比较(P均<0.05),但0.6倍组、0.8倍组与前一剂量组比较(P均>0.05)。0.4倍组早产儿治疗后的40周龄神经功能NBNA评分均高于未用组、0.2倍组、0.6倍组、0.8倍组,差异具有显著性(P均<0.05)。未用组、0.2倍组、0.4倍组、0.6倍组、0.8倍组早产儿的不良反应率分别为4.16%、3.85%、3.22%、22.72%、27.78%,未用组、0.2倍组、0.4倍组早产儿治疗期间不良反应率低于0.6倍组、0.8倍组,差异具有显著性(P均<0.05)。结论重组人促红细胞生成素可通过降低脑损伤早产儿炎性反应和改善神经功能相关指标来起到脑细胞修复作用,0.4倍重组人促红细胞生成素说明书参考剂量治疗早产儿脑损伤的预后更佳,且不良反应较少。

Objective To analyze the safe dose of recombinant human erythropoietin in the treatment of brain injury in premature infants. Methods A retrospective study was conducted on 121 premature infants with brain injury(ischemic brain injury delivered in Department of obstetrics and Gynecology of the Second Affiliated Hospital of Harbin Medical University from January 2017 to October 2018). They were divided into two groups: the treatment group without recombinant human erythropoietin(24 cases) and the reference dose of recombinant human erythropoietin instructions(750 U/kg·d) group with 0.2 times, 0.4 times, 0.6 times and 0.8 times, respectively. They were called 0.2 times group, 0.4 times group, 0.6 times group and 0.8 times group. The number of cases was 26 cases, 31 cases, 22 cases and 18 cases, respectively. The serum neurological function related indexes, serum inflammatory related factors, 40-week-old neurological function and adverse reactions were compared before and after treatment. Results Serum neurological function(DP, EP, NSE) and inflammatory related factors(IL-6, TNF-α, hs-CRP) were compared: the unused group, 0.2 times group, 0.4 times group, 0.6 times group and 0.8 times group decreased in turn. The unused group, 0.2 times group and 0.4 times group were compared with the former dose group(all P<0.05), but the 0.6 times group and 0.8 times group were compared with the former dose group(all P>0.05). The NBNA scores of 40-week-old preterm infants in 0.4 times group after treatment were higher than those in unused group, 0.2 times group, 0.6 times group and 0.8 times group(all P<0.05). The adverse reaction rates of preterm infants in unused group, 0.2 times group, 0.4 times group, 0.6 times group and 0.8 times group were 4.16%, 3.85%, 3.22%, 22.72% and 27.78%, respectively. The adverse reaction rates of preterm infants in unused group, 0.2 times group and 0.4 times group were lower than those in 0.6 times group and 0.8 times group(all P<0.05). Conclusion Recombinant human erythropoietin can play a role in brain cell repair by reducing inflammatory response and improving neurological function in premature infants with brain injury. The reference dose of 0.4 times rhEPO instruction has better prognosis and fewer adverse reactions in the treatment of premature infants with brain injury.