Neonatal Hypothermia

A Method to Provide Neuroprotection After Hypoxic Ischemic Encephalopathy

Katherine M. Newnam, MS, RN, CPNP, NNP-BC; Donna L. DeLoach, MS, RN, CPNP, NNP-BC


NAINR. 2011;11(3):113-124. 

In This Article

Previous Research Using Animal Models

Rodent mice had unilateral carotid artery ligation with measured exposure to periods of hypoxia to replicate related injury sustained during perinatal asphyxia and HIE. Histologic findings of rodent mice and neuroimaging studies of infants who demonstrated symptoms of HIE demonstrated similar injury patterns of the basal ganglia and cerebral cortex.[13,21,22] These findings were important when examining magnetic resonance imaging (MRI) studies after a diagnosis of HIE.

In similar models using fetal sheep, Gunn et al[23] described evidence to support neuroprotection. After a 30-minute hypoxic insult, followed by hypothermia (defined as a reduction of brain temperature of 2–5°C within 90 minutes of the hypoxic insult), significant improvement in clinical outcomes was demonstrated when compared with lambs that were provided sham cooling.[20,23]

It has also been noted in experimental studies using animal model that a delay of treatment of 6 or more hours did not demonstrate the same level of neuroprotection.[24,25] Cytotoxic edema as well as clearly described apoptotic cascades was demonstrated as a result of the hypoxic insult. Of important note, there were minimal adverse outcomes related to the cooling process using the animal models, and side effects were minimal and easily monitored or treated. Many of the side effects (bradycardia, oliguria, arrhythmia, and thrombocytopenia) were consistent among the treatment and control groups, supporting that these side effects were the result of the hypoxic injury and not the result of hypothermia treatment.

These findings have provided researchers evidence to move ahead with clinical trials, with the goal of successfully halting the continued damage occurring during the second stage of HIE. This critical time was replicated in initial human trials (pilot studies) and was, therefore, used during hypothermia protocol development. Testing of the hypothermia protocols was completed during large randomized controlled clinical trials described in more detail later in this article (see Table 1).[14,26,27]

We understand that the degree of injury as well as the individual response to that injury can be variable, making long-term outcomes difficult to predict for these infants. It would be easy to say that all infants who had any degree of hypoxia at birth would qualify for intensive evaluation and care including serial follow-up; however, that is neither practical nor cost-effective. We must determine a reasonable prediction method to offer those infants most at risk with the appropriate services.


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