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

Disclosures

NAINR. 2011;11(3):113-124. 

In This Article

Pathophysiology of HIE

We understand from previous research (clinical and experimental) that primary cell death occurs within minutes after having a loss of oxygen before or during the infant's delivery (see Fig 1). The primary causes of the loss of oxygen or hypoxia are usually related to an unforeseen event before or at delivery, such as cord compression or shear; placental abruption; maternal physiologic compromise such as preeclampsia/eclampsia, temperature/infection, maternal hemorrhage, or delivery complications such as entrapment.[11]

Figure 1.

Pathophysiology of HIE.

The cerebral blood flow (CBF) of adults is typically maintained at constant levels despite fluctuations in the systemic blood pressure. However, in the infant, CBF autoregulation is not as responsive; therefore, when hypoxia occurs, the infant's initial systemic response is to maintain perfusion to the brain and end organs through a redistribution of cardiac output. This compensation is accomplished with increased heart rate (to increase cardiac output) and the endogenous release of epinephrine. Although initially effective, these measures can only maintain CBF for a short time (minutes), and when the hypoxic state persists, the systemic blood pressure falls and neuronal cells are damaged through progressive intracellular energy failure and eventual cell death via apoptosis.[8,12,13]

This progressive hypoxic state begins the rapid depletion of high-energy metabolites (anaerobic metabolism) and rapid depletion of adenosine triphosphate; hypoxic depolarization of cells; cytotoxic edema or cell swelling; and intracellular accumulation of calcium, extracellular accumulation of neurotransmitters (glutamate), and additional by-products of the necrotic tissue (see Fig 1).[14,15]

When the cerebral circulation and oxygenation are restored (reperfusion), the slow reduction of the metabolic acidosis occurs as evident by the slow recovery of previous impairment from cerebral oxidative metabolism. This is clinically demonstrated by reduced cell swelling or cytotoxic edema and the reduction of the excitatory amino acids that initially accumulated in the extracellular spaces (see Fig 1). It is now clear that although neuronal cell death occurs during this primary or first phase of hypoxia, it is the second or latent stage of the insult, which leads to global damage.[3] Infants who did not show recovery from the initial hypoxic as demonstrated by persistent and profound acidosis showed universally adverse outcomes.[16]

This second or latent stage of this process, which occurs 6 to 24 hours after the initial insult, is the recovery of cerebral circulation and oxygenation leading to a progression of inflammatory response and significant cerebral edema, onset of seizures, secondary cytotoxic edema, and additional cell death.[8,17,18] This particular injury has been described as an evolving process, but evidence so far describes a period between the first and second stage of injury as a "therapeutic window," which was based on earlier animal models using primarily fetal sheep and infant rats.[19,20] The critical timing of this latent phase has been a key finding during research using animal models.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....