How to prognosticate hypoxic brain injury?

Prognostication of Hypoxic Brain Injury

A comprehensive multimodal approach including clinical examination, electrophysiological tests, biomarkers, and neuroimaging is essential for accurate prognostication of hypoxic brain injury, with no single factor serving as the sole indicator for patient prognosis. 1

Initial Assessment and Timing

• Rule out potential confounding factors before prognostication, including sedatives, significant electrolyte disturbances, and hypothermia, to prevent an overly pessimistic prognosis 1
• Perform daily clinical/neurological assessments for patients undergoing targeted temperature management, with the most crucial evaluation conducted after rewarming 1
• Avoid early prognostication, as it can lead to self-fulfilling prophecy bias, where test results indicating poor outcomes influence treatment decisions prematurely 1

Clinical Examination Components

• Pay special attention to pupillary and corneal reflexes, which are strong predictors of neurological outcome 1
• Absence of pupillary and corneal reflexes at ≥72 hours post-injury strongly suggests unfavorable neurological outcome 1
• Status myoclonus within 72 hours post-injury is associated with poor prognosis 1
• Motor response remains a robust indicator even in sedated patients and correlates well with injury severity 1

Electrophysiological Testing

• Bilateral absence of N20 cortical waves in somatosensory evoked potentials (SSEP) at ≥24 hours strongly indicates poor outcome 1
• Highly malignant EEG patterns at >24 hours post-injury are associated with unfavorable outcomes 1
• EEG patterns such as status epilepticus, burst suppression, and electrocerebral silence demonstrate high specificity (92-99%) for predicting disability and death, though sensitivities are low (6-39%) 2

Biomarkers

• Neuron-specific enolase (NSE) levels exceeding 60 μg/L at 48h or 72h indicate poor prognosis 1
• In ECMO patients, NSE values are often higher due to ongoing hemolysis, and the threshold for predicting unfavorable outcomes may exceed 100 μg/L 1
• Other biomarkers such as neurofilament light chain or tau protein may be useful, but data in hypoxic brain injury patients is limited 1

Neuroimaging

• Non-contrast head CT should be performed initially but has limited sensitivity for non-hemorrhagic axonal injury or hypoxic-ischemic encephalopathy 3
• Brain MRI shows characteristic patterns depending on the severity of the injury and is more sensitive than CT for detecting all stages of subarachnoid hemorrhage, extra-axial collections, contusions, and axonal injuries 3
• Extensive diffuse anoxic injury observed on brain CT/MRI is associated with poor outcomes 1

Prognostication Algorithm

1. First 24-72 hours: Focus on stabilization and avoid definitive prognostication

   • Maintain systolic blood pressure >110 mmHg 4, 3
   • Prevent and correct hypoxemia (SaO₂ <90%) 4, 3
   • Begin targeted temperature management if indicated 1

2. After 72 hours or after rewarming:

   • Perform comprehensive neurological examination focusing on brainstem reflexes 1
   • Conduct electrophysiological testing (EEG, SSEP) 1
   • Measure biomarkers (NSE) 1
   • Obtain brain MRI if not already performed 3

3. Poor prognosis is indicated by at least two of the following:

   • Absent pupillary and corneal reflexes at ≥72h 1
   • Bilateral absence of N20 SSEP responses at ≥24h 1
   • Highly malignant EEG pattern at >24h 1
   • NSE >60 μg/L at 48h or 72h 1
   • Status myoclonus ≤72h 1
   • Extensive diffuse anoxic injury on neuroimaging 1

Special Considerations

• For patients on ECMO, especially after ECPR, prognostication is more challenging and may require higher thresholds for biomarkers 1
• Frequent meetings with family/surrogate decision-makers are essential, focusing on informed consent, goal-setting with timelines, and emotional support 1
• Decisions regarding withdrawal of life-sustaining therapy should be highly individualized with multidisciplinary discussions and consideration of patient preferences 1
• Be aware that the overall prognosis for hypoxic-ischemic brain injury is extremely poor, with only about 25% of patients surviving to hospital discharge, often with severe neurological or cognitive deficits 5

Common Pitfalls to Avoid

• Avoid relying on a single prognostic indicator, as this can lead to inaccurate predictions 1
• Be cautious of the "self-fulfilling prophecy" bias, where early negative prognostication leads to withdrawal of care that might have been beneficial 1
• Remember that despite negative CT results, patients with neurologic abnormalities should be closely observed, as CT has limited sensitivity for certain types of brain injury 3
• Consider that up to 27% of patients with normal CT findings may have abnormalities detected on subsequent MRI 3