HYPOTHERMIA FOR ASPHYXIA

Objective: This lecture will cover the results of the two published trials of hypothermia for hypoxic ischemic encephalopathy recently reported. There will be a discussion of the methods of selection, criteria, and outcomes of the studies, as well as future directions for further trials.

Methods: Review of the literature.

Results: Numerous studies in small and large animal models have shown efficacy for hypothermia as a neuroprotective therapy. Recently, two large studies were completed in humans following similar protocols for inclusion and exclusion except that one trial cooled primarily the head and the other cooled the body systemically. The former trial also used a further step in selection of newborns, background abnormalities or seizures evident on an amplitude integrated EEG. Only term newborns were enrolled who had no evidence of being in extremis or other underlying abnormalities, like genetic diseases. In both studies, babies had to be enrolled before 6 hours of life, and were “cooled” for 72 hours. There were no serious adverse events of the hypothermia in either trial. The major outcomes of mortality and severe disability were tabulated at 18 months of life. In the selective head cooling trial, although there was no treatment effect when all patients were counted, there was a significant improvement seen when only babies determined to have moderate encephalopathy by aEEG were compared to the randomized controls. However, in the systemic cooling trial, there was a treatment effect for all babies with the combined end point of death or moderate or severe disability, but not when these parameters were looked at individually. There are two other trials still ongoing in Australia and the United Kingdom. Long term effects of these therapies are currently unknown but there will be follow up studies done for both of the published trials.

Conclusion: Hypothermia is safe and may prove effective in reducing neurodevelopmental disability. There does not seem to be a shift toward increasing survivors with disability in either trial. Long term follow up is needed, and babies should not be cooled unless enrolled in a standardized protocol.

Keywords: perinatal: aEEG; outcome; hypoxia-ischemia