新生儿缺氧缺血性脑病不同复温时间亚低温治疗临床效果的前瞻性随机对照研究

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy:a prospective randomized controlled study

目的探索新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)不同复温时间亚低温治疗的临床效果。方法前瞻性收集2018年1月—2022年1月在厦门大学附属中山医院出生的101例亚低温治疗(mild therapeutic hypothermia,MTH)的HIE新生儿,随机分为MTH1组(50例,10 h复温,0.25℃/h)和MTH2组(51例,25 h复温,0.10℃/h),比较两组临床特征和临床效果,并对复温第25小时振幅整合脑电图(amplitude-integrated electroencephalogram,aEEG)正常睡眠觉醒周期(sleep-wake cycle,SWC)的出现情况进行二元logistic回归分析。结果MTH1组和MTH2组胎龄、5 min Apgar评分、中重度HIE占比等比较差异无统计学意义(P>0.05)。短期临床疗效方面,与MTH2组比较,MTH1组复温结束时动脉血pH值更趋于正常,氧依赖时间更短,复温第10、25小时正常SWC占比更高,出生后第5、12、28天的NBNA评分更高(P<0.05);两组复温相关惊厥发作率等比较差异无统计学意义(P>0.05)。中期临床疗效方面,两组第6个月的神经系统伤残率和第3、6个月的Bayley婴儿发展量表Ⅲ评分比较差异无统计学意义(P>0.05)。二元logistic回归分析显示,25 h复温时间不利于正常SWC的出现(OR=3.423,95%CI:1.237~9.469,P=0.018)。结论与25 h复温时间相比,10 h复温时间短期临床效果更好。延长MTH复温时间对中重度HIE新生儿的临床效益有限且不利于正常SWC的出现,不宜作为常规处理。

Objective To investigate the clinical efficacy of mild therapeutic hypothermia(MTH)with different rewarming time on neonatal hypoxic-ischemic encephalopathy(HIE).Methods A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital,Xiamen University,from January 2018 to January 2022.These neonates were randomly divided into two groups:MTH1 group(n=50;rewarming for 10 hours at a rate of 0.25°C/h)and MTH2 group(n=51;rewarming for 25 hours at a rate of 0.10°C/h).The clinical features and the clinical efficacy were compared between the two groups.A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle(SWC)on amplitude-integrated electroencephalogram(aEEG)at 25 hours of rewarming.Results There were no significant differences between the MTH1 and MTH2 groups in gestational age,5-minute Apgar score,and proportion of neonates with moderate/severe HIE(P>0.05).Compared with the MTH2 group,the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming,a significantly shorter duration of oxygen dependence,a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming,and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5,12,and 28 after birth(P<0.05),while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups(P>0.05).There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age(P>0.05).The binary logistic regression analysis showed that prolonged rewarming time(25 hours)was not conducive to the occurrence of normal SWC(OR=3.423,95%CI:1.237-9.469,P=0.018).Conclusions Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours.Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC,and therefore,it is not recommended as a routine treatment method.