Neuroprotective Strategies for Hypoxic Ischemic Encephalopathy

Leslie Parker, PhD, NNP-BC; Carole Kenner, DNS, RNC-NIC, FAAN

Disclosures

NAINR. 2012;12(1):8-11. 

In This Article

Abstract and Introduction

Abstract

Our world is shrinking due to computerized linkages and the mobility of society. Information is shared rapidly around the world. Issues surrounding newborn and infant nursing are global. In efforts to acknowledge the international community, each Newborn and Infant Nursing Review issue will feature a column that highlights care-related issues from a featured country or region of the world. This article focuses on the United States. Newborn and infant health issues are global ones. To review issues occurring in different areas of the world, a different area of the globe will be featured that addresses the Newborn and Infant Nursing Review's theme-oriented topic. This month the United States will be featured. Our guest author is Ms Leslie Parker PhD, NNP-BC, Clinical Assistant Professor, College of Nursing at the University of Florida and a Regional Network Contact for the Council of International Neonatal Nurses for the United States. This month's article focuses on the hypoxic ischemic encephalophathy.

Introduction

Hypoxic ischemic encephalophathy (HIE) is a potentially devastating condition occurring in one to four infants per 1000 live births.[1] Despite recent advances in obstetric and neonatal care,[2] HIE remains an important cause of morbidity and mortality during the neonatal period. Hypoxic ischemic encephalophathy accounts for 25% of all neonatal deaths and contributes to significant financial and personal burden. Ten to fifteen percent of infants affected by HIE will die before discharge from the hospital; an additional 10% to 15% will develop cerebral palsy; and 40% will be affected by blindness, deafness, autism, epilepsy, developmental delay, or other long-term complications.[3,4] The etiology of HIE varies but is most often due to an acute perinatal episode such as placental abruption, prolapsed cord, uterine rupture, acute blood loss, or shoulder dystocia.[5]

Hypoxic ischemic encephalophathy may be due to any condition leading to decreased oxygen supply (hypoxia) and decreased blood supply (ischemia).With hypoxia and ischemia, the brain converts to anaerobic metabolism, resulting in depletion of adenosine triphosphate and accumulation of lactic acid and free radicals.[6] In addition, failure of intracellular pump function allows sodium, calcium, and water to accumulate in brain cells, leading to cellular death.[7] Intracellular pump failure also causes excess release of neurotoxic excitatory neurotransmitters such as glutamate.[6]

Hypoxic ischemic encephalophathy is not a single event but an evolving process. It begins with the initial insult, progresses into a latent phase, and finally occurs as a secondary injury phase. The initial insult causes neural cellular death and apoptosis due to metabolic activity failure, increased levels of excitatory neurotransmitters and free radicals, inflammation, and intracellular pump failure. During the latent phase, the infant may appear stable; however, electroencephalography (EEG) activity remains suppressed, and hypoperfusion and reduced oxygen consumption continue.[8] The latent phase is considered a window of opportunity for initiation of neuroprotective strategies designed to interrupt the process of cellular death that occurs during the final phase. Although the exact timing or length of the latent phase is unknown, the currently accepted estimation is from 6 hours to 3 days. Because of this uncertainty, it is recommended that neuroprotective treatments be initiated as soon as possible after the initial insult.

After the latent phase, the secondary or delayed phase of injury occurs and continues over the next several days. During this phase, cerebral edema, cerebral mitochondrial dysfunction, inflammation, overproduction of excitatory neurotransmitters, and free radical production result in the death of neural cells that survived the initial injury phase.[6,9]

Symptoms of HIE include renal failure; decreased cardiac function and hypotension; hematologic disorders, including disseminated intravascular coagulation and clotting abnormalities; and decreased liver function. Typical neurologic symptoms include early and often refractory seizures, hypotonia, respiratory depression and apnea, and a depressed level of consciousness.[6,9,10] Both the short- and long-term prognosis of HIE is largely dependent on the severity and length of the initial insult.

Until recently, treatment of HIE consisted of supportive care, including respiratory support, treatment of hypotension, careful monitoring of fluid and electrolytes, and treatment of seizures. In the last decade, the use of hypothermia for treatment of HIE has received considerable focus and has been shown to improve the neurologic outcome of infants with mild to moderate HIE. The benefits of hypothermia are compelling, and it is beginning to be viewed as a standard of care for term infants with HIE.[11,12] The mechanism of hypothermic neuroprotection includes decreased rate of cellular death, decreased cerebral metabolism, conservation of adenosine triphosphate stores, and limited free radical release.[6,11]

Hypothermia should be initiated as soon as possible and no later than 6 hours after the initial insult. Hypothermia can be performed by selective head cooling or total body cooling. Although both methods are effective, total body cooling allows hypothermia at a deeper level, which may prove more beneficial.[5] During hypothermia, infants are cooled at 34°C to 35°C for 48 to 72 hours and then rewarmed over the next 12 to 24 hours.

Potential complications of hypothermia include hemodynamic changes such as decreased heart rate, cardiac output and stroke volume, renal impairment, acid-based and electrolyte imbalances, and coagulation abnormalities.[13,14] Although potentially problematic, these complications have not caused undue harm to infants in clinical trials, and abnormalities are expected to return to baseline upon rewarming. In general, facilities providing hypothermia to infants with HIE should have specific protocols in place, and staff should be well educated concerning selection criteria, cooling and rewarming procedures, and monitoring for complications.

Although hypothermia has improved the prognosis of infants with mild and moderate HIE, it has not impacted the outcome of those severely affected, nor has it completely eliminated the risk of death or long-term neurologic sequelae. Many infants are not candidates for hypothermia; these include infants older than 6 hours and those born premature. Additional therapies that provide neuroprotection for infants affected by HIE are thus critically needed. Although no other established treatment currently exists, several potential therapies, including Epogen, magnesium sulfate, allopurinol, and stem cell transplantation, are currently being investigated.

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