Implementation And Initial Results Of Mild Hypothermia Treatment To Reduce Acute Brain Injury In Neonatal Hypoxic Ischemic Encephalopathy At High Altitude

Background: Mild hypothermia has become a routine treatment in neonatal hypoxic ischemic encephalopathy(HIE)in advanced countries in the past decade,but not been used at high altitude worldwide.High altitude hypoxia and relatively poor socio-economic conditions would result in high incidence of HIE with more severity.We first assessed brain injury while preparing for implementing mild hypothermia in HIE at Women’s and Children’s Hospital of Qinghai Province(average altitude 3000m).Methods: We prospectively examined video EEG for 72 hours,cerebral oxygen saturation and flow velocity of middle cerebral artery once a day for 3 days,and cerebral MRI at admission and before discharge in 26 full term HIE patients(age 1 to 34 hours,median 3 hours,9(35%)of them older than 6 hours.The altitude ranged from 1800 to 3000,median 2260 meters)during August 2014 to December 2014 in Women’s and Children’s Hospital of Qinghai Province.These patients were used as Control Group.Implementation of mild hypothermia was initiated in January2015.A total of 37 HIE patients were admitted to NICU and approached for mild hypothermia during January 2015 to March 2016.Among them,20 patients aged 0.75 to 29(median 2.75,3 more than 6 hours after birth)hours(altitude 1800~3700 meters,median 2260 meters)consented mild hypothermia treatment(Cooling Group).Due to the fairly long time that parents spent in considering the treatment and giving consent,mild hypothermia treatment was delayed to 3~79 hours after birth(median 12.75 hours),and 16(80%)of them later than 6 hours.Mild hypothermia was maintained for 72 hours and rewarming for 6~12 hours.Assessments of brain function in control group were repeated.Results: According to clinical grading,Control Group included 8 mild,6 moderate and 12 severe degree of HIE.Cooling Group included 1 mild,3 moderate and 16 severe degree of HIE.More children Cooling Group had moderate or severe degree than Cooling Group(P=0.037).As compared to Control Group,Cooling Group had significantly lower amplitude of EEG background(P=0.013),fewer sharp waves(P=0.05),higher cerebral oxygen saturation(P<0.0001),lower cerebral artery blood flow velocity(P left =0.0006,P right =0.0015)during the 72 hours treatment,and less degree of brain injury by MRI(P=0.048)at 1 week after birth.No significant correlation was found between admission age,residence altitude and treatment results(P>0.1).Conclusions: The brain damage in HIE was serious at high altitude.Mild hypothermia significantly reduced brain injury in HIE patients.The initial implementation of mild hypothermia was difficult largely due to poor cultural and socioeconomic conditions.The treatment window extended to more than 6 hours after birth remains effective in HIE patients.