Hypoxic-Ischemic Brain Injury 

 Definition

Hypoxic-Ischemic Brain Injury (HIBI) refers to diffuse or focal neuronal injury resulting from reduced oxygen delivery and/or reduced cerebral blood flow leading to failure of oxidative metabolism and cellular energy failure.

It is one of the most common causes of global brain injury in ICU, especially after:

• Cardiac arrest (most important)
• Severe hypoxemia
• Shock states
• Respiratory failure
• Near drowning
• Carbon monoxide poisoning
• Severe anemia

 Pathophysiology 

HIBI is not a single event. It occurs in two phases:

👉 Primary Injury

Occurs during hypoxia/ischemia itself

👉 Secondary Injury

Occurs during reperfusion (major determinant of outcome)

 Cerebral Oxygen Delivery Physiology

Cerebral Oxygen Delivery Formula-CDO₂=CBF×CaO₂

Where:

• CBF = Cerebral Blood Flow
• CaO₂ = Arterial oxygen content

Oxygen Content Equation-CaO2 =(1.34×Hb×SaO2 )+(0.003×PaO2 )

👉 Hence HIBI can occur due to:

 Vulnerable Brain Regions (Selective Neuronal Vulnerability)

Some neurons have higher metabolic demand → more vulnerable.

Most vulnerable

1. Hippocampus (CA1 neurons)
2. Cerebellar Purkinje cells
3. Basal ganglia
4. Cortical pyramidal neurons
5. Watershed areas

 Types of Brain Edema in HIBI

HIBI produces mixed edema pattern:

Cytotoxic edema

• Early phase
• Cellular swelling

Vasogenic edema

• Later phase
• BBB breakdown

 Clinical Spectrum

Depends on severity and duration.

Mild Injury

• Confusion
• Memory impairment
• Cognitive dysfunction

Moderate Injury

• Coma
• Myoclonus
• Seizures
• Movement disorders

Severe Injury

• Persistent coma
• Brain death
• Vegetative state

 Post-Cardiac Arrest Syndrome 

HIBI is the major determinant of survival after cardiac arrest.

Post-cardiac arrest syndrome includes:

1. Brain injury
2. Myocardial dysfunction
3. Systemic ischemia-reperfusion injury
4. Persistent precipitating cause

 Neurological Manifestations Timeline

Immediate

• Coma
• Absent reflexes

24–72 hours

• Myoclonic status epilepticus
• Cerebral edema
• Raised ICP

Days to weeks

• Cognitive decline
• Movement disorders
• Vegetative state

 Diagnostic Evaluation

A. Clinical Examination

Brainstem Reflexes

B. Neuroimaging

CT Brain

Early:

• Loss of grey-white differentiation
• Sulcal effacement

Severe:

• Diffuse cerebral edema
• Pseudo-subarachnoid sign

MRI Brain (Gold Standard)

Especially:Diffusion Weighted Imaging (DWI)

Shows:

• Cytotoxic edema
• Restricted diffusion
• Early detection

 EEG Findings

Used for:

• Seizure detection
• Prognostication

Poor prognostic patterns:

• Burst suppression
• Status epilepticus
• Non-reactive EEG
• Generalized suppression

 Biomarkers

Neuron-specific enolase -(NSE)S-100 protein

Used for prognostication (not standalone).

 Prognostication (Guideline Based – ERC/AHA)

Prognosis should be assessed ≥72 hours after ROSC and after sedation clearance.because early neurological findings are unreliable due to confounding factors such as sedation, targeted temperature management (TTM), metabolic disturbances, and delayed neuronal injury evolution, which can lead to false pessimistic prediction.

Poor Outcome Predictors

Two or more required:

• Absent pupillary reflex
• Absent corneal reflex
• Bilateral absent N20 SSEP
• Highly malignant EEG
• Elevated NSE
• Diffuse anoxic injury on MRI

 Management Principles

There is NO direct curative therapy. Management aims to:

• Prevent secondary injury
• Optimize cerebral perfusion
• Control ICP
• Maintain homeostasis

 ICU Management — Core Strategy

A. Airway and Oxygenation

Target:

• SpO₂: 94–98%
• Avoid hyperoxia (PaO₂ >300 harmful)

B. Hemodynamic Management

Maintain cerebral perfusion pressure.

Target:

• MAP ≥ 65 mmHg
• Often 70–80 preferred in HIBI

C. Temperature Management 

Targeted Temperature Management (TTM)

Indicated in:

• Comatose post-cardiac arrest patients

Recommended Target

36°C is currently guideline supported
(Previously 32–34°C)

Avoid fever at all costs.

Mechanism

TTM reduces:

• Metabolic demand
• Excitotoxicity
• Free radical formation
• Apoptosis

D. Glucose Control

Target:

• 140–180 mg/dL

Avoid hypoglycemia (very harmful to brain).

E. Seizure Control

Common in HIBI.

Treatment:

• Continuous EEG monitoring
• Antiepileptics
• Aggressive seizure suppression

F. Ventilation Targets

• Normocapnia (PaCO₂ 35–45)
• Avoid hypocapnia (reduces CBF)

G. ICP Management

Similar to TBI principles:

• Head elevation
• Osmotherapy
• Sedation
• Avoid hypotension
• Controlled ventilation

 Role of Osmotherapy

Both used:

Mannitol

Hypertonic saline

Used for:

• Raised ICP
• Cerebral edema

(Not disease modifying for neuronal injury)

 Complications of HIBI

Early

• Seizures
• Cerebral edema
• Autonomic instability

Late

• Persistent vegetative state
• Spasticity
• Parkinsonism
• Cognitive impairment

 Special Syndromes

Lance-Adams Syndrome

• Chronic post-hypoxic myoclonus
• Occurs in survivors
• Better prognosis

Myoclonic Status Epilepticus

• Occurs early post arrest
• Poor prognosis

 Duration of Ischemia vs Outcome

(Temperature modifies tolerance)

Pathology

Gross findings:

• Diffuse cerebral edema
• Laminar cortical necrosis
• Hippocampal neuronal loss
• Basal ganglia injury