Therapeutic Normothermia for infants with HIE

We are all well aware of the use of therapeutic hypothermia for infants with HIE, so what the heck do I mean “therapeutic normothermia”??

In the Randomized Control Trials (RCT’s) performed around the world to establish the effectiveness of therapeutic hypothermia, like any other randomized trial, there were two study groups.  One group recieved the standard of care (the control group), and one group that was cooled to 33.5 degrees C for 72 hours (the intervention group).

As you know, the intervention group has better outcomes and less death than the control, standard of care group… but there was another group… that had the worst outcomes of all.  This was the group of babies in the “standard of care” (control) arm who had temperatures that exceeded 37.5 degrees C.

The post-hoc analysis of the NICHD Whole Body Cooling trial (1) discovered that for infants with moderate to severe HIE who were not cooled and had increased temperatures had an increased risk of death or disability.

To summarize the conclusions of this secondary analysis (1) , it was found that control infants had a mean esophageal temperature of 37.2 +/- 0.7 (36.5 to 37.9) degrees C over the 72-hour period. And that 63% of all core temperatures recorded were >37 degrees C; 22% were >37.5 degrees C; and and 8% were >38 degrees C.  When looking at the mean skin temperature similar results were found – 12% of all skin temperatures were >37 degrees C, 5% were >37.5 degrees C, and 2% were >38 degrees.  The final analyis found that the odds of death or disability were increased 3.6-4 fold (this is 360 to 400 times higher) for each 1 degrees C increase in the skin or esophageal temperatures.

So what does this mean to us today… although I would like to believe that every infant who is eligible for therapeutic hypothermia receives it, this is not the reality (especially in remote and resource poor environments).  This study shows us that just as therapeutic hypothermia is a life-sparing treatment for those infants that receive it, the exact opposite is true, those who do not receive it and are exposed to elevated body temperature (due to infection, equiment malfunction, or other reason) have the worst outcomes of all.  We need to take all precautions necessary to provide therapeutic normothermia to the babies in our care, especially those term infants born at highest risk; and this applies to those infants we cool too and caution should be taken in the days following rewarming to avoid elevated temperatures at all costs.

Temperature is a powerful metabolic force in the body and should not be considered a soft vital-sign to be dismissed as less important than others.  In fact, as this analysis reveals, temperature can especially be dangerous to the injured, newborn brain.


  1. Laptook A, et al. (2008) Elevated temperature after hypoxic-ischemic encephalopathy: risk factor for adverse outcomes. Pediatrics. Sep;122(3):491-9. doi: 10.1542/peds.2007-1673.

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