Pilot study of treatment with whole body hypothermia for neonatal encephalopathy

Background. There is extensive experimental evidence to support the investi gation of treatment with mild hypothermia after birth asphyxia. However, cl inical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypot hermia. Objectives. The objectives of this study were to determine whether it is fe asible to select infants with a bad neurological prognosis and to begin hyp othermic 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 in tegrated electroencephalography (aEEG), and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognost ic of a bad outcome. Rectal temperature was maintained at 33.2 +/- (standar d deviation).6 degrees C for 48 hours. Rectal and tympanic membrane tempera ture, blood pressure, heart rate, blood gases, blood lactate, full blood co unt, 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 (MR I) and neurological examination. Results. All infants selected to receive hypothermia developed convulsions and a severe encephalopathy. During 48 hours of hypothermia infants had pro longed 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 potassiu m levels (median value: 3.9 mmol . L-1). Hypothermia was associated with lo wer heart rate and higher mean blood pressure. However, these changes did n ot seem to be clinically relevant and no significant complication of hypoth ermia was encountered. Blood viscosity and coagulation studies were similar during and after cooling. Unusual MRI findings were noted in 3 infants: tr ansverse sinus thrombosis with subsequent small cerebellar infarct; probabl e thrombosis in the straight sinus; and hemorrhagic cerebral infarction. Si x of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination; 3 infants died and 1 had major abnormalities. No ne of the 6 infants with a normal aEEG developed severe neonatal encephalop athy or neurological sequel. Conclusions. After birth asphyxia infants can be objectively selected by aE EG 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 abnormal ities. Further studies of both the safety and efficacy of mild hypothermia, including further neuroimaging studies, are warranted.