Head Cooling for HIE

Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalo-pathy: multicentre randomized trial.
Lancet (Feb 19, 2005); 365:663-70. Full Text

BACKGROUND: Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia. We did a multicentre randomised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy.

METHODS: 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography (aEEG) were randomly assigned to either head cooling for 72 h, within 6 h of birth, with rectal temperature maintained at 34-35 degrees C (n=116), or conventional care (n=118). Primary outcome was death or severe disability at 18 months. Analysis was by intention to treat. We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before randomisation--i.e., severe loss of background amplitude, and seizures--and those with less severe changes.

FINDINGS: In 16 babies, follow-up data were not available. Thus in 218 infants (93%), 73/110 (66%) allocated conventional care and 59/108 (55%) assigned head cooling died or had severe disability at 18 months (odds ratio 0.61; 95% CI 0.34-1.09, p=0.1). After adjustment for the severity of aEEG changes with a logistic regression model, the odds ratio for hypothermia treatment was 0.57 (0.32-1.01, p=0.05). No difference was noted in the frequency of clinically important complications. Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes (n=46, 1.8; 0.49-6.4, p=0.51), but was beneficial in infants with less severe aEEG changes (n=172, 0.42; 0.22-0.80, p=0.009).

INTERPRETATION: These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy, it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes.

Comments. This is the first of several large randomized-controlled trials investigating the safety and efficacy of using hypothermia to prevent death or disability from perinatal hypoxic-ischemic encephalopathy (HIE). This trial used head cooling as it’s method of hypothermia, and used aEEG as well as clinical findings to select eligible patients. The results showed a modest trend toward improved outcomes in the head cooling group, and statistical significance was only reached in the subgroup with LESS-SEVERE aEEG changes. Stated differently, babies with aEEG evidence of severe HIE (“severe loss of background amplitude, and seizures”) were not likely to benefit from head cooling)! Compare these results with the next paper which used Whole-Body Hypothermia for HIE. ABK.

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