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PEDIATRICS Vol. 106 No. 4 October 2000, pp. 684-694
Received May 24, 1994; accepted Jan 10, 2000.
, and
From the * Department of Paediatrics and the Biomedical
Sciences Division, Imperial College School of Medicine, London, United
Kingdom.
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°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 · L1) and
low blood potassium levels (median value: 3.9 mmol · L1). 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°C to 34°C is associated with minor physiologic abnormalities. Further studies of both the safety and efficacy of mild hypothermia, including further neuroimaging studies, are warranted. Key words: hypothermia, neonatal encephalopathy, birth asphyxia, amplitude integrated electroencephalography.
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