What is the treatment for hypoxic encephalopathy?

Treatment for Hypoxic Encephalopathy

The treatment of hypoxic-ischemic encephalopathy (HIE) should focus on therapeutic hypothermia as the cornerstone therapy, with additional supportive care including management of seizures, respiratory support, and careful prognostication.

Initial Management

• Position the patient with a 20-30° head-up tilt to optimize cerebral perfusion while minimizing intracranial pressure 1
• Maintain systolic blood pressure >110 mmHg to prevent secondary cerebral insults and preserve cerebral blood flow 1
• Ensure adequate oxygenation with appropriate respiratory support to prevent hypoxemia, which significantly worsens neurological outcomes 1
• Target PaCO₂ of 4.5-5.0 kPa; hyperventilation should only be used short-term when there is evidence of raised intracranial pressure 1
• Use 0.9% saline as the crystalloid of choice for fluid management to prevent increases in brain water 1

Therapeutic Hypothermia

• Therapeutic hypothermia is the standard of care for moderate to severe hypoxic-ischemic encephalopathy 2, 3
• Cooling should be initiated within 6 hours of the hypoxic event to be effective 2, 3
• Maintain strict temperature control at 33-34°C for 72 hours 2, 3
• Rewarming should occur gradually over at least 4 hours 2
• Therapeutic hypothermia reduces the risk of death or major neurodevelopmental disability by approximately 22-33% 3
• For every 5-7 infants treated with therapeutic hypothermia, one fewer infant will die or have significant neurodevelopmental disability 3

Seizure Management

• If the EEG shows a treatable non-convulsive status epilepticus, antiepileptic treatment should be administered 2
• Epileptic seizures that affect quality of life should be treated, even with a poor prognosis 2
• Anticonvulsant therapy should be administered at a sufficiently high dose and for a sufficiently long period of time 2
• In palliative therapy, alternative modes of administration for anticonvulsants (buccal, intramuscular, subcutaneous or rectal) can be considered 2

Delirium Management

• Before using drug therapies in delirious patients, implement general measures such as a calm environment that promotes orientation, fall prevention, and calm communication 2
• Perform EEG to differentiate between hypoactive delirium and a treatable non-convulsive status epilepticus 2
• Base the indication for drug therapy on symptoms and impact on quality of life 2

Prognostication

• Avoid early prognostication as it can lead to self-fulfilling prophecy bias 1, 4
• Perform daily clinical/neurological assessments, with the most crucial evaluation conducted after rewarming if targeted temperature management was implemented 4
• Rule out confounding factors before prognostication, including sedatives, significant electrolyte disturbances, and hypothermia 1, 4
• Use a comprehensive approach including clinical examination, electrophysiological tests, biomarkers, and neuroimaging 4
• Poor prognosis is indicated by at least two of the following: absent pupillary and corneal reflexes at ≥72h, bilateral absence of N20 SSEP responses at ≥24h, highly malignant EEG pattern at >24h, NSE >60 μg/L at 48h or 72h, status myoclonus ≤72h, or extensive diffuse anoxic injury on neuroimaging 4

Special Considerations

Neonatal HIE

• Cooling should only be conducted in facilities with capabilities for multidisciplinary care 2
• Required resources include: intravenous therapy, respiratory support, pulse oximetry, antibiotics, anticonvulsants, and pathology testing 2
• The assessment of HIE and prognosis should be multidimensional according to current guidelines, including cerebral imaging, EEG, and laboratory determination of neuron-specific enolase 2

Adult HIE

• For patients with severe brain injury perceived to be devastating, a period of physiological stabilization and observation is recommended to improve the quality of decision-making 1
• During the observation period, the therapeutic aim is to provide cardiorespiratory stability to facilitate accurate neurological prognostication 1

Common Pitfalls to Avoid

• Avoid relying on a single prognostic indicator, as this can lead to inaccurate predictions 4
• Prevent even short periods of hypoxia, as they can exacerbate secondary brain injury 1
• Avoid hypovolemia and hypotension, as hypovolemic brain-injured patients do not tolerate transfer well and hypotension will adversely affect neurological outcome 1
• Be cautious of the "self-fulfilling prophecy" bias, where early negative prognostication leads to withdrawal of care that might have been beneficial 4

Emerging Therapies

• Several neuroprotective agents are being explored as adjuncts to hypothermia, including melatonin, allopurinol, topiramate, erythropoietin, N-acetylcysteine, magnesium sulfate, and xenon 5
• These experimental treatments aim to reduce free radical production and have anti-inflammatory and anti-apoptotic actions 5