Therapeutic hypothermia for hypoxic-ischaemic encephalopathy in the newborn infant

This review examines recent findings from experimental models and clinical trials of induced hypothermia as treatment after cerebral hypoxia-ischaemia in term newborn infants.

Experimental hypothermia inhibits many steps in the biochemical cascade that produces severe brain injury after hypoxia-ischaemia. This is in contrast to pharmacological agents, which tend to target only one step in the process that leads to brain injury. In adult humans hypothermia initiated immediately after cardiac arrest has improved outcomes. Delayed cooling after brain trauma has also been effective in a subgroup of adult patients. Seventy-two hours of selective head cooling with mild systemic hypothermia (rectal temperature 34.5 degrees C) in term infants with hypoxic-ischaemic encephalopathy (HIE) reduced death or disability in the infants with less severe electroencephalographic changes at entry (no benefit in those with advanced electroencephalographic changes). Cooling had no apparent adverse effects. A smaller randomized clinical trial of 48 h whole body cooling (rectal T 33 degrees C) found a reduction in death and neurological impairment.

In term infants with HIE there is emerging evidence that both selective head cooling and whole body cooling are neuroprotective and safe. This is consistent with a wealth of experimental animal data and adult trials. Neuroprotection seems to be lost if cooling is started after 6 h. The challenge now is to complete ongoing trials. If meta-analysis confirms a therapeutic effect, then this may lead to selection criteria and treatment protocols for very early hypothermia in HIE at term.