Ischemic Brain Injury: Hemodynamic & Oxygenation

• Neuronal injury after an ischemic insult is a dynamic process that can continue for hours to days.
• The brain accounts for 15% of the body's cardiac output and uses 20% of the body's oxygen, despite being only 2% of body weight.
• ATP depletion from cerebral ischemia disrupts osmotic gradients, leading to water influx into cells, causing cytotoxic edema.
• Cytotoxic edema peaks 48-72 hours post-injury.
• The Monro-Kellie doctrine states that the skull is a fixed-volume container, so increases in brain, blood, or CSF volume must be offset by reductions in other components, or ICP will rise.
• Elevated ICP reduces cerebral perfusion pressure (CPP = MAP – ICP), which lowers blood flow and worsens ischemia.

Hemodynamic & Oxygenation Targets

• Maintain MAP >65 mmHg and CPP >60 mmHg to ensure adequate cerebral blood flow.
• Target PaO2 range is 80–120 mmHg and oxyhemoglobin saturation in the high 90s to avoid both hypoxemia and hyperoxemia.
• Excess oxygen generates reactive oxygen species, worsening neuronal injury.

ICP Management Strategies

• A stepwise approach to managing elevated ICP includes:
  • Optimizing positioning, such as 30° head elevation.
  • Providing analgesia/sedation.
  • Using hypertonic therapy with mannitol or hypertonic saline.
  • Administering barbiturates.
  • Initiating hypothermia (TTM).
  • Considering surgical decompression.
• Therapeutic hyperventilation is appropriate only for life-threatening cerebral herniation or severe ICP elevation as a short-term bridge to definitive therapy, targeting a PaCO2 of 35–40 mmHg.

Seizures & Temperature Control

• Treat acute seizures with IV lorazepam and avoid prophylactic antiepileptics, using continuous EEG if seizures are suspected.
• Fever increases metabolic demand and inflammation, exacerbating secondary injury, so treat temperatures >38°C with acetaminophen.
• Targeted temperature management (TTM) involves maintaining comatose cardiac arrest survivors at 33-36°C for 24 hours in the ICU to reduce metabolic demand and improve outcomes.

Prognostication & Family Communication

• Neurological prognostication is unreliable before 72 hours post-normothermia, as early exams lack accuracy, and delayed neuronal injury and recovery timelines require prolonged observation.
• Withdrawal of life-sustaining treatment due to perceived poor neurological prognosis is the most common cause of death in cardiac arrest survivors.
• Emergency physicians should set realistic expectations, emphasize uncertainty in early prognosis, and advocate against premature care withdrawal when communicating with families.

Guidelines & Outcomes

• AHA, ERC, and ESICM provide post-cardiac arrest care guidelines, based on ILCOR's CoSTR recommendations.
• Survival rates for out-of-hospital cardiac arrest are 12% (75% with favorable neurology), while in-hospital cardiac arrest survival is 25%.
• Standardized post-resuscitation protocols improve survival and neurological recovery by addressing multisystem insults, such as hemodynamics, temperature, and seizures.

Miscellaneous Key Points

• The three components of intracranial volume are brain (~80%), blood (~10%), and CSF (~10%).
• The final consequence of uncontrolled intracranial hypertension is cerebellar tonsillar herniation through the foramen magnum, compressing medullary cardiorespiratory centers.
• No neuroprotectant therapy has succeeded in clinical trials, as none have shown reproducible clinical benefit despite targeting molecular pathways in ischemic injury.
• Cerebral arteriolar vasodilation worsens ICP by increasing cerebral blood volume, raising ICP, and further reducing CPP, forming a vicious cycle.
• Stroke and traumatic brain injury (TBI) share overlapping pathophysiology with hypoxic-ischemic brain injury.
• Compensatory mechanisms, such as shifting CSF to the spinal subarachnoid space and reducing venous blood volume, delay ICP elevation initially.

Neuronal injury after ischemia is a dynamic process. ATP depletion disrupts osmotic gradients, leading to cytotoxic edema, peaking 48-72 hours post-injury. Elevated ICP reduces cerebral perfusion pressure, worsening ischemia. Maintain MAP >65 mmHg and CPP >60 mmHg.