A Randomized Clinical Trial of Therapeutic Hypothermia During Transport for Hypoxic Ischemic Encephalopathy (HIE): Device-regulated Cooling Versus Standard Practice.

Statement of the Problem:

Hypoxic ischemic encephalopathy (HIE) remains a major cause of death and severe disability despite advances in neonatal and perinatal medicine. Therapeutic hypothermia is the single most promising intervention for HIE. Reduction of brain temperature by 2° to 5°C has shown to be neuroprotective in newborn and adult animal models of brain ischemia. Therapeutic hypothermia instituted within 6 hours of birth has been shown to significantly improve survival and neurodevelopmental outcome in term newborns with HIE. Hypothermia is most effective if begun during the latent period, before secondary energy failure. It is not known whether cooling initiated after 6 hours of age is effective. Animal studies have shown that the sooner the initiation of cooling, the better the outcome. They have also suggested that the latent period may be shorter with a more severe insult. Cooling should be initiated as soon as possible, preferably within 2 hours and not later than 6 hours. There have been six large randomized clinical trials supporting the efficacy of therapeutic hypothermia for HIE and it is now the standard of care in the U.S. and internationally.

Once a patient qualifies for cooling, whole body cooling or selective head cooling is initiated. However, most birth hospitals do not have the ability to provide therapeutic hypothermia; thus, patients must be transported to Level 3 NICUs specially equipped to provide this therapy. As there is a limited therapeutic window for induction of hypothermia, it would be ideal to initiate therapeutic hypothermia as soon as the patient qualifies for cooling therapy. If cooling is initiated at the birth hospital, neuroprotective temperatures can be achieved several hours prior to arrival in the cooling center.

At this time patients cooled in transport receive passive cooling (turning off the active warming devices such as the transport isolette) or active cooling (ice packs placed around the baby). These practices have been shown to present a significant risk for over-cooling and under-cooling. The risks associated with excessive cooling include bradycardia, cardiac arrest, and coagulation disturbances. Undercooling likely results in reduced efficacy of the neuroprotective effects provided by therapeutic hypothermia.

Primary and secondary endpoints Primary end point: The percentage of temperatures in the target range (33°-34°C) both within and between enrolled infants after cooling initiation by the transport team.