What is Hypoxic-Ischemic Encephalopathy (HIE)?

From the Guidelines

Hypoxic-Ischemic Encephalopathy (HIE) is a neurological condition characterized by brain injury resulting from a lack of oxygen and blood flow to the brain, typically as a consequence of a cardiac arrest 1.

Key Characteristics

• The condition is diagnosed based on a multidimensional assessment, including cerebral imaging, electroencephalogram (EEG), and laboratory determination of neuron-specific enolase 1.
• The prognosis is determined using a standard prognostic algorithm, and if the assessment shows no prospect of recovery of cerebral functions and regaining consciousness, a therapy limitation should be discussed with the relatives 1.

Treatment and Management

• Antiepileptic treatment should be attempted if the EEG shows a treatable non-convulsive status epilepticus 1.
• Epileptic seizures that occur during the course of the disease and affect quality of life should be treated, even with a bad prognosis 1.
• Alternative modes of administration, such as buccal, intramuscular, subcutaneous, or rectal, can be considered for anticonvulsant therapy in palliative care 1.

Associated Conditions

• Delirium is a common complication of HIE, and its treatment should consist of non-medicinal and medicinal components 1.
• Haloperidol can be an option for treatment of hyperactive delirium, but there is currently no pharmaceutical therapeutic option for hypoactive delirium 1.

From the Research

Definition and Overview of Hypoxic-Ischemic Encephalopathy (HIE)

• Hypoxic-Ischemic Encephalopathy (HIE) is a condition that results in brain damage in newborns due to insufficient blood and oxygen supply during or after birth 2.
• HIE is a major cause of neurological disability and mortality in newborns, with over one million neonatal deaths occurring annually worldwide 2.
• The incidence of HIE is approximately 1 to 3 per 1000 live births 3, and it is more common in low- and middle-income countries, with an incidence 3-10 fold higher than in high-income settings 4.

Pathophysiology and Classification of HIE

• The pathophysiology of HIE involves different phases, including the primary phase, latent phase, secondary phase, and tertiary phase 2.
• The primary and secondary phases are characterized by episodes of energy and cell metabolism failures, increased cytotoxicity and apoptosis, and activated microglia and inflammation in the brain 2.
• HIE is classified into mild, moderate, and severe categories based on the extent of brain damage and resulting neurological issues 2.

Treatment and Management of HIE

• Therapeutic hypothermia (TH) is the standard of care and the only currently available therapy to reduce the risk of death or disability in newborns with moderate to severe HIE 3.
• TH needs to be initiated within 6 hours after birth in order to provide the best chance for neuroprotection 3.
• Maintenance of homeostasis is important in order to prevent conditions that may result in additional brain injury, and seizures are common in neonates with HIE, but electrographic seizures are rare in the first few hours after birth if the insult occurred during labor and delivery 3.

Research and Future Directions

• Understanding the cellular and molecular aspects of the different phases of HIE is crucial for developing new interventions and therapeutics 2.
• Emerging evidence from preclinical studies suggests that future therapy for HI brain injury and neonatal encephalopathy will combine novel neuroprotective and anti-seizure agents 5.
• More research is needed to address the question of whether therapeutic hypothermia should be used as a preventive treatment to reduce adverse outcomes in mild-HIE 4.