Pilot study of treatment with whole body hypothermia for neonatal encephalopathy
Pilot study of treatment with whole body hypothermia for neonatal encephalopathy
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DOI：
10.1542/peds.106.4.684
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发表时间：
2000-10-01
期刊：
影响因子：
8
通讯作者：
Edwards, AD
中科院分区：
文献类型：
--
作者：
Azzopardi, D;Robertson, NJ;Edwards, AD
背景有大量的实验证据支持对出生窒息后进行亚低温治疗的研究。然而，由于难以预测出生后不久的长期结局以及对低血糖不良反应的担忧，临床研究一直被推迟。本研究的目的是确定选择神经预后不良的婴儿并在出生后6小时内开始低温治疗是否可行，并观察这种治疗对相关生理变量的影响。通过振幅整合脑电图（aEEG）评估了16名具有出生窒息临床特征的新生儿（中位数脐带血pH值：6.74;范围：6.58-7.08），在10名aEEG预后不良的婴儿中，在出生后6小时内开始轻度全身低温。直肠温度保持在33.2 +/-（标准差）.6 ℃持续48小时。在冷却期间和冷却后监测直肠和鼓膜温度、血压、心率、血气、血乳酸、全血细胞计数、血电解质、高和低剪切速率粘度和凝血研究。通过重复的磁共振成像（MRI）和神经系统检查对神经系统结局进行初步评估。所有选择接受低温治疗的婴儿都出现了抽搐和严重的脑病。在48小时的低体温婴儿有长期的代谢性酸中毒（中位数pH值：7.30;碱过剩：-6.3 mmol。L-1，高血乳酸（中位数乳酸：5.3 mmol . L-1）和低血钾水平（中位数：3.9 mmol . L-1）。体温过低与较低的心率和较高的平均血压有关。然而，这些变化似乎与临床无关，也没有出现明显的低体温并发症。冷却期间和冷却后的血液粘度和凝血研究相似。3名婴儿出现不寻常的MRI表现：横窦血栓形成伴随后的小小脑梗死;直窦可能血栓形成;出血性脑梗死。10名冷却婴儿中有6名仅出现轻微异常或随访神经系统检查正常; 3名婴儿死亡，1名婴儿出现严重异常。6例aEEG正常的新生儿均未发生严重新生儿脑病或神经系统后遗症。aEEG可客观地筛选出出生后窒息的婴儿，在发生严重新生儿脑病的高危婴儿中，在出生后6小时内开始低温治疗。长期轻度低温至33 ℃至34 ℃与轻微的生理异常有关。进一步研究的安全性和有效性的轻度低温，包括进一步的神经影像学研究，是必要的。
Background. There is extensive experimental evidence to support the investigation of treatment with mild hypothermia after birth asphyxia. However, clinical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypothermia.Objectives. The objectives of this study were to determine whether it is feasible to select infants with a bad neurological prognosis and to begin hypothermic therapy within 6 hours of birth, and to observe the effect of this therapy on relevant physiologic variables.Methods. Sixteen newborn infants with clinical features of birth asphyxia (median cord blood pH: 6.74; range: 6.58-7.08) were assessed by amplitude integrated electroencephalography (aEEG), and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognostic of a bad outcome. Rectal temperature was maintained at 33.2 +/- (standard deviation).6 degrees C for 48 hours. Rectal and tympanic membrane temperature, blood pressure, heart rate, blood gases, blood lactate, full blood count, blood electrolytes, high and low shear rate viscosity, and coagulation studies were monitored during and after cooling. A preliminary assessment of neurological outcome was made by repeated magnetic resonance imaging (MRI) and neurological examination.Results. All infants selected to receive hypothermia developed convulsions and a severe encephalopathy. During 48 hours of hypothermia infants had prolonged metabolic acidosis (median pH: 7.30; base excess: -6.3 mmol . L-1, a high blood lactate (median lactate: 5.3 mmol . L-1) and low blood potassium levels (median value: 3.9 mmol . L-1). Hypothermia was associated with lower heart rate and higher mean blood pressure. However, these changes did not seem to be clinically relevant and no significant complication of hypothermia was encountered. Blood viscosity and coagulation studies were similar during and after cooling. Unusual MRI findings were noted in 3 infants: transverse sinus thrombosis with subsequent small cerebellar infarct; probable thrombosis in the straight sinus; and hemorrhagic cerebral infarction. Six of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination; 3 infants died and 1 had major abnormalities. None of the 6 infants with a normal aEEG developed severe neonatal encephalopathy or neurological sequel.Conclusions. After birth asphyxia infants can be objectively selected by aEEG and hypothermia started within 6 hours of birth in infants at high risk of developing severe neonatal encephalopathy. Prolonged mild hypothermia to 33 degrees C to 34 degrees C is associated with minor physiologic abnormalities. Further studies of both the safety and efficacy of mild hypothermia, including further neuroimaging studies, are warranted.