What is the diagnosis and treatment for Hypoxic-Ischemic Encephalopathy (HIE)?

From the Guidelines

Hypoxic-ischemic encephalopathy (HIE) treatment should prioritize therapeutic hypothermia for newborns, and for adults, treatment should focus on addressing the underlying cause, maintaining adequate oxygenation and blood pressure, and preventing secondary brain injury, as recommended by the most recent guidelines 1.

Key Considerations

• The prognosis assessment of HIE should be performed using a standard prognostic algorithm, considering cerebral imaging, electroencephalogram (EEG), and laboratory determination of neuron-specific enolase 1.
• If the prognosis assessment shows no prospect of recovery of cerebral functions and regaining consciousness, a therapy limitation should be discussed with the relatives, taking into account comorbidities 1.
• For adults with HIE, treatment should include maintaining adequate oxygenation and blood pressure, and preventing secondary brain injury through measures like targeted temperature management (36°C for 24 hours) 1.
• Epileptic seizures that occur during the course of the disease and affect quality of life should be treated, even with a bad prognosis, but anticonvulsant therapy should not affect quality of life more than the seizures 1.

Treatment Recommendations

• Therapeutic hypothermia is now standard care in high-income countries for the treatment of moderate or severe hypoxic ischemic encephalopathy in term and near-term infants 1.
• For newborns, therapeutic hypothermia should be initiated within 6 hours of birth, with strict temperature control to a specified range (typically 33 °C–34 °C) and most commonly for a duration of 72 hours with rewarming over at least 4 hours 1.
• Adoption of hypothermia techniques without close monitoring, without protocols, or without availability of comprehensive neonatal intensive care may lead to harm 1.

Quality of Life Considerations

• The state of delirium can be frightening and upsetting for patients, relatives, and professional team members, and open communication and explanation of the clinical situation are therefore enormously important 1.
• Before the use of drug therapies in delirious patients, possible general measures such as a calm environment that promotes orientation, prophylaxis against falls, and calm communication should be carried out 1.
• The indication for drug therapy should be based on the symptoms and the quality of life, and alternative forms of application can be used to a greater extent 1.

From the Research

Definition and Incidence of Hypoxic-Ischemic Encephalopathy

• Hypoxic-ischemic encephalopathy (HIE) is a brain lesion caused by inadequate blood supply and oxygen deprivation, often occurring in neonates 2.
• The incidence of HIE is approximately 1 to 8 per 1000 live births in developed countries 3, and 10-20 per 1000 live births in low and middle-income countries 4.

Pathophysiology of Hypoxic-Ischemic Encephalopathy

• The pathophysiology of HIE involves impaired cerebral blood flow and oxygen delivery to the brain, resulting in primary and secondary energy failure 5.
• HIE pathophysiology also involves oxidative stress, mitochondrial energy production failure, glutaminergic excitotoxicity, and apoptosis 4.
• Other mechanisms contributing to the onset and progression of HIE include reperfusion injury, inflammation, mitochondrial dysfunction, excitotoxicity, ferroptosis, endoplasmic reticulum stress, and apoptosis 2.

Treatment and Management of Hypoxic-Ischemic Encephalopathy

• Hypothermia therapy is the sole standard treatment for neonatal HIE, providing only partial neuroprotection 2, 6.
• Systemic supportive care, including the use of inotropes, vasopressors, and fluid boluses, is also important in the management of HIE 6.
• Experimental treatments, such as drug therapy and stem cell therapy, are being explored as adjunctive treatments to hypothermia therapy 2, 5.
• Monitoring of patients with HIE during and after hypothermia is possible using near-infrared spectroscopy, echocardiography, electrocardiography, and magnetic resonance imaging 6.

Prognosis and Outcomes of Hypoxic-Ischemic Encephalopathy

• The prognosis for infants with HIE is poor, with 40-60% of affected infants dying by 2 years of age or having severe disabilities 5.
• Hypothermia therapy can improve outcomes in some cases, but the treatment is only partially effective, with not more than 50% of neonates achieving an improved outcome 4.
• Further research is needed to better understand the long-term impact of experimental treatments and to improve outcomes in infants with HIE 5.