亚低温联合促红细胞生成素治疗足月儿缺氧缺血性脑病的安全性观察

Safety observation of therapeutic hypothermia conjunction with erythropoietin injection in the treatment of termneonatal hypoxic ischemic encephalopathy

目的研究亚低温联合促红细胞生成素(EPO)治疗中、重度足月儿缺氧缺血性脑病(HIE)的安全性,为开展多中心研究亚低温联合EPO治疗足月儿HIE的疗效奠定基础。方法对2012年2月至2015年3月收住复旦大学附属儿科医院NICU满足亚低温治疗标准并知情同意下的中、重度足月儿HIE随机分组。实验组给予亚低温治疗72 h联合EPO(1 000 U·kg-1,静脉滴注,隔天1次,14 d);对照组给予亚低温治疗72 h和与EPO同等剂量、同样给药方法的生理盐水。监测患儿治疗期间的生命体征,治疗期间放弃治疗事件,记录亚低温治疗前、亚低温治疗结束时、EPO疗程结束后的血生化指标,观察严重心律失常、大静脉血栓、不可纠正的低血压、死亡等严重不良事件,低血压、凝血功能障碍、肾功能异常等一般不良事件。比较两组间不良事件发生率的差异。结果 44例足月儿HIE进入本文安全性观察,其中实验组25例,对照组19例。3例重度HIE足月儿(实验组2例,对照组1例)亚低温治疗期间主动放弃治疗。两组在EPO相关不良事件血生化指标Hb、RBC、Hct和PLT差异均无统计学意义;两组在HIE并发症及其治疗严重和一般不良事件的发生率差异均无统计学意义。结论亚低温联合EPO治疗中、重度足月儿HIE未发生与治疗相关的严重不良事件,安全可行。

Objective To investigate the safety of therapeutic hypothermia （TH） conjunction with erythropoietin injection in the treatment of moderate to severe hypoxic ischemic encephalopathy （HIE） in term neonates and to lay the foundation for the multi-center study of the efficacy of combination therapy. Methods Term neonates who were admitted to NICU of Children＇ s Hospital of Fudan University from February 2012 to March 2015 and met the TH treatment criteria were included and grouped by randomization after signing the informed consent. The trial group received TH treatment （72 h） combined with EPO （ 1 000 U·kg-1 , ivgn. QOD × 14 d） ; and the control group received TH treatment （72 h） and placebo （saline） with the same dosage and usage as EPO. Vital signs, homological and biochemical index, serious adverse events （severe arrhythmia, major vein thrombosis, refractory hypotension and death ） and HIE complications of the treatments were recorded and analyzed between two groups. Results Forty-four term neonates with HIE were admitted for TH treatment with 25 patients received added EPO and the rest received placebo. No statistical significance in the levels of hemoglobin, red blood cells, hematocrit and platelet between the two groups was observed. There was no statistical significance in the serious adverse events and HIE complications either. Conclusion Serious adverse events related to the treatment were not found with the treatment of TH conjunction with EPO for HIE, It is safe and feasible to start a multi-center study on the efficacy of TH combined with EPO in HIE treatment.