Elevated intracranial pressure and brain herniation

Intracranial pressure (ICP) is the pressure that exists within the cranium, including its compartments (e.g., the subarachnoid space and the ventricles). ICP varies as the position of the head changes relative to the body and is periodically influenced by normal physiological factors (e.g., cardiac contractions). Adults in the supine position typically have a physiological ICP of ≤ 15 mm Hg; an ICP of ≥ 20 mm Hg indicates pathological intracranial hypertension. ICP may be elevated in a variety of conditions (e.g., intracranial tumors) and can result in a decrease in cerebral perfusion pressure (CPP) and/or herniation of cerebral structures. Symptoms of elevated ICP are generally nonspecific (e.g., impaired consciousness, headache, vomiting); however, more specific symptoms may be present depending on the affected structures (e.g., Cushing triad if the brainstem is compressed). Findings from brain imaging (e.g., a midline shift) and physical examination (e.g., papilledema) can indicate ICP elevation but may not be able to rule it out. Therefore, ICP monitoring and quantification are vital in at-risk patients. Management usually involves expedited surgery of resectable or drainable lesions, conservative measures (e.g., positioning, sedation, analgesia, and antipyretics), and medical therapy (e.g., hyperosmolar therapy such as mannitol or hypertonic saline, or glucocorticoids). Treatment options for refractory intracranial hypertension include temporary controlled hyperventilation, CSF drainage, and decompressive craniectomy (DC), as well as other advanced medical therapies (e.g., barbiturate coma, therapeutic hypothermia).

• Idiopathic intracranial hypertension
• CNS inflammation, infection, and/or abscess
• Space-occupying lesions
  • Intracranial hemorrhage or hematoma
  • Aneurysm
  • Intracranial tumors
• Elevated venous pressure (e.g., as a result of heart failure)
• Increased CSF (hydrocephalus)
• Metabolic disturbances; (e.g., hyponatremia, hepatic encephalopathy)
• Epilepsy and seizures ^[1]

Physiology of ICP ^[2]

• Overview
  • Physiological ICP is ≤ 15 mm Hg in adults (in supine position); children generally have a lower ICP.
  • ICP varies depending on the position of the head relative to the rest of the body and is influenced by certain physiological processes (e.g., cardiac contractions, sneezing, coughing, Valsalva maneuver).
  • Volume of intracranial contents ^[2]
    • Brain: approx. 85%
    • CSF: approx. 10%
    • Blood: approx. 5%
• Monro-Kellie principle: The sum of volumes of intracranial blood, CSF, and brain within the cranium is constant, which means that an increase in one component volume will be compensated for by a decrease in other(s). ^[3]
  • Initial compensation allows for an increase in component volume with minimal change in ICP.
    • Decrease in CSF volume via shifting into the spinal canal
    • Decrease in cerebral blood volume via venous vasoconstriction and drainage
  • Once the compensatory mechanisms are exhausted, ICP increases rapidly because of the skull's inability to expand and accommodate the increase in intracranial volume.

Physiology of cerebral blood flow

• Cerebral blood flow (CBF): the volume of blood (in mL) supplied to 100 g of brain tissue per minute ^[4]
• Cerebral autoregulation
  • Process by which CBF is constantly maintained across a wide range of mean arterial pressures (MAPs), typically between 50–150 mm Hg
  • Decreases in MAP cause vasodilation and increases in MAP trigger precapillary vascular constriction within seconds.
• Cerebral perfusion pressure (CPP): the effective pressure that delivers blood to the brain and is responsible for constant perfusion of brain tissue
  • CPP = MAP - ICP
  • A CPP of 0 equals the absence of brain perfusion.
  • Cerebral perfusion is predominantly modulated by the partial pressure of carbon dioxide (pCO₂).
  • CPP linearly increases with pCO₂ until pCO₂ > 90 mm Hg. ^[2]
    • Increased pCO₂ → ↓ pH → vasodilation → ↑ cerebral blood flow to remove excess CO₂
    • Decreased pCO₂ → vasoconstriction → ↓ cerebral blood flow
  • Cerebral perfusion is, to a lesser degree, modulated by brain temperature through cerebral metabolism. ^[5]
    • Hyperthermia → ↑ cerebral metabolism → ↑ CBF → ↑ cerebral blood volume → ↑ ICP
    • Mild hypothermia → ↓ cerebral metabolism → ↓ CBF → ↓ cerebral blood volume → ↓ ICP
  • Partial pressure of oxygen (pO₂) only modulates cerebral perfusion in severe hypoxic conditions when pO₂ < 50 mm Hg.

Therapeutic hyperventilation reduces pCO₂ → ↓ cerebral blood flow → ↓ intracranial pressure (used, e.g., when patients with acute cerebral edema are unresponsive to other treatments).

Consequences of elevated ICP

• Decreased cerebral perfusion CPP
  • If arterial pressure remains constant, an increase in ICP will cause a decrease in CPP.
  • ↓ CPP → ↓ CBF → ischemia
• Brain tissue herniation
  • Increased pressure gradient within the rigid skull → brain tissue shifts to other spaces of the skull → brain tissue herniation
  • This may result in injury or in blocking of cerebral vessels and subsequent ischemia.
• Cushing's reflex
  • ↑ ICP → ↓ CPP → compensatory activation of the sympathetic nervous system → ↑ systolic blood pressure → stimulation of aortic arch baroreceptors → activation of the parasympathetic nervous system (vagus) → bradycardia ^[6]
  • ↑ Pressure on brainstem → dysfunction of respiratory center → irregular breathing

• Global
  • Cushing triad: irregular breathing, widening pulse pressure,; and bradycardia
  • Reduced levels of consciousness
  • Headache
  • Vomiting
  • Papilledema
  • Psychiatric changes
  • In infants: macrocephaly, bulging fontanel, sunset sign
• Focal
  • Diplopia
  • Cerebral herniation syndrome: see “Subtypes and variants” below.

Cerebral herniation syndromes ^[7][8]

Subfalcine herniation

• Most common type of cerebral herniation
• Mass effect due to affection of the ipsilateral frontal, parietal, or temporal lobes → medial displacement of the cingulate gyrus → herniation under the falx cerebri → compression of:
  • Anterior cerebral artery branches (specifically the pericallosal artery) → contralateral hemiparesis (predominantly lower limbs)
  • Contralateral hemisphere → obstruction of the foramen of Monro → hydrocephalus
• Usually no pupillary involvement

Descending transtentorial herniation

• Uncal herniation: mass effect caused by a supratentorial lesion → medial and downward displacement of the uncus at the tentorial incisure
  • Early manifestations
    • Ipsilateral posterior cerebral artery compression→ cortical blindness with contralateral homonymous hemianopia
    • Ipsilateral oculomotor nerve compression → Hutchinson pupil (ipsilateral fixed and dilated pupil)
    • Ipsilateral cerebral peduncle compression → contralateral hemiparesis
    • Midline shift → altered consciousness
  • Late manifestations
    • Contralateral cerebral peduncle compression against the tentorial notch → Kernohan phenomenon (a rare false localizing sign consisting of hemiparesis ipsilateral to the brain lesion)
    • Downward shift of the brainstem → brainstem hemorrhages → focal deficits, impaired consciousness, death
• Central herniation: mass effect caused by bilateral or midline supratentorial lesions or severe brain edema → downward displacement of the diencephalon, midbrain, and pons
  • Oculomotor nerve compression → oculomotor nerve palsy with fixed and dilated pupils
  • Brain stem dysfunction → decerebrate or decorticate posture, cardiac arrest, respiratory failure → vegetative state or death
  • Stretching or tearing of basilar artery perforating branches → Duret hemorrhages

Foramen magnum herniation

• Structures of the posterior fossa (e.g., cerebellar tonsils, medulla) herniate through the foramen magnum
• Symptoms include:
  • Impaired consciousness
  • Decerebrate posturing
  • Apnea
  • Impaired circulation
  • Death

The following clinical features should raise suspicion for a cerebral herniation syndrome, which can be fatal if not treated promptly: acutely worsening level of consciousness (e.g., coma), pupillary changes (e.g., ipsilateral mydriasis, fixed dilated pupils), new focal neurological deficits (e.g., hemiparesis, decerebrate posturing), and cardiorespiratory compromise (e.g., bradycardia, apnea).

Neuroimaging (CT head/MRI head) ^[9]

• Indications
  • Clinical features of increased ICP
  • Suspected intracerebral pathology: e.g., neurological compromise, seizures, head trauma
  • See also “Diagnostics in TBI.”
• Neuroimaging findings of intracranial hypertension: indirect indicators of elevated ICP and cerebral edema
  • Midline shift
  • Mass lesions
    • TBIs: e.g., EDH, SDH, ICH, parenchymal contusions
    • CNS infections: e.g., brain abscess
    • Brain tumors (with or without surrounding vasogenic edema)
  • Effacement of the basilar cisterns
  • Effacement of cerebral sulci
  • Evidence of brain herniation (e.g., uncal herniation or tonsillar herniation)
  • Changes in ventricular size (e.g., enlarged with hydrocephalus, reduced with diffuse cerebral edema)

Clinical examination and imaging may indicate elevated ICP, but cannot rule it out. Additionally, neither allow ICP to be quantified, which is necessary to determine CPP.

Invasive ICP monitoring

• Invasive monitoring is typically required for confirmation and accurate measurement of ICP.
• ICP should be evaluated in combination with CPP to guide therapeutic interventions and help prevent secondary brain injury and brain herniation. ^[10]
• There are no absolute contraindications for invasive ICP monitoring.
• Consider the risks versus the benefits in consultation with a specialist.

Indications ^[11][12][13]

• Traumatic brain injury: ICP monitoring in severe TBI reduces in-hospital and two-week postinjury mortality. ^[12]
• Mass lesions: e.g., brain tumors, ICH, SAH, SDH, EDH
• Diffuse brain injury due to:
  • Infectious causes: e.g., meningitis, encephalitis
  • Vascular causes: e.g., ischemic stroke, cerebral venous thrombosis
  • Other causes: e.g., hydrocephalus, idiopathic intracranial hypertension
• Other: nonsurgical intracranial hemorrhages in patients who cannot undergo full clinical evaluation

Methods to monitor ICP ^[10][14][15]

Intraventricular catheters; with an external ventricular drain (EVD) and intraparenchymal catheters; (IPC) are most commonly used to monitor ICP, as they have the highest accuracy compared with other monitoring methods.

• Intraventricular catheter: a monitoring device placed into the ventricles of the brain along with a CSF drainage system (i.e., an EVD) ^[16]
  • Allows for continuous ICP monitoring and evaluation of intracranial compliance
  • Useful in conditions in which CSF drainage is required for both diagnostic and therapeutic purposes
  • The preferred monitoring method for intracranial lesions associated with hydrocephalus ^[10]
  • Complications
    • Infections
    • Hemorrhage attributable to the placement of the device
    • Malpositioning and/or accidental removal
    • Blockage with blood or debris
• Intraparenchymal catheter: a fiberoptic device placed into the brain parenchyma without an accompanying CSF drainage system ^[17]
  • Allows for continuous ICP monitoring
  • Accuracy and effect on patient outcomes are considered equivalent to intraventricular catheters
  • Lower risk of infection and hemorrhage compared with intraventricular catheters
  • Technical complications: e.g., dislodgement, breakage

Interpretation

• Generally, ICP > 20 mm Hg indicates intracranial hypertension, which requires treatment. ^[10]
• ICP varies in a complex cyclical manner and is influenced by hemodynamic and metabolic factors.
• Monitor ICP along with MAP to calculate CPP using the formula CPP = MAP − ICP.

Do not use the ICP value in isolation as a prognostic marker or to inform therapeutic decisions. ^[10]

Approach ^{[9][10][12][18][19][20]}

• Indications for ICP management
  • Clinical or radiographic signs of elevated ICP
  • Confirmed elevated ICP on direct measurement
• Goals: Maintain cerebral blood flow (CBF) and prevent secondary brain injury.
• Acute resuscitation and stabilization: Follow the ABCDE approach.
  • Emergency airway management (e.g., if GCS < 8): high-risk, as laryngeal manipulation can raise ICP (see “Intubation of patients with increased ICP”)
  • Mechanical ventilation as needed: See “Ventilation strategy for elevated ICP.”
  • Hemodynamic support: See “Shock.”
• Consultation: Early involvement of neurosurgery and a neurocritical care specialist is essential.

• General therapeutic targets: Base treatment decisions on trends identified using repeat assessments of ICP, CPP, and clinical status. ^[10][12]
  • Target ICP: < 20 mm Hg
  • Target CPP range: 60–70 mm Hg

Conservative therapy ^[23]

See also “Neuroprotective measures.”

• Patient positioning :
  • Head of bed elevation (∼ 30°): ^[18][24]
    • Reduces ICP without compromising CBF
    • Blunts the effect of high PEEP on ICP
    • Should be avoided if the patient is hypovolemic
  • Avoid neck flexion and rotation and situations that may provoke a Valsalva response.
• Sedation and analgesia ^[18]
  • Prevents unnecessary spikes in ICP due to pain, agitation, and patient-ventilator dyssynchrony
  • Combinations of benzodiazepines, opioid analgesics, and dexmedetomidine are generally used.
  • Ketamine was previously contraindicated, but recent evidence suggests that it may be suitable for use.
  • Propofol may be used but caution should be taken when using high doses because of the risk of hypotension. ^[12]
  • Minimize waking patients up for neurological assessments.^[10][24]
  • See “Adjunctive care of ventilated patients” for dosages and further information.
• Temperature management: : Maintain normothermia; fever should be treated with antipyretics.
• Fluid management: Target euvolemia and avoid serum hypoosmolarity.
• Seizure control
  • Manage acute seizures with antiepileptics and consider prophylaxis for patients at high risk of seizures.
  • Routine seizure prophylaxis is not recommended.

Medical therapy ^[23]

• Hyperosmolar therapy
  • Indications
    • Elevated ICP refractory to conservative measures
    • Empiric therapy for patients with elevated ICP and herniation syndrome or neurological deterioration ^[12]
  • Options ^[25][26][27]
    • IV hypertonic saline (HTS) ^[28][29]
    • IV mannitol

Although hyperosmolar therapies can lower ICP, they have not been shown to improve neurological outcomes in patients with underlying TBI, acute ischemic stroke, ICH, SAH, or hepatic encephalopathy. ^[23]

• Glucocorticoids: e.g., dexamethasone
  • Recommended only if elevated ICP is caused by vasogenic edema secondary to: ^[20][35]
    • CNS infection or inflammation (e.g., bacterial or tuberculous meningitis) ^[23]
    • Neoplasms
  • Avoid in patients with ICH. ^[23]
  • Not recommended in large hemispheric stroke ^[24]
  • Contraindicated in TBI (associated with increased mortality) ^[12]

Surgical therapy

• Emergency surgery (if possible): e.g., resection of brain tumor, hematoma evacuation ^[20]
• CSF drainage
  • Indications ^[22]
    • Acute obstructive hydrocephalus (can be caused by TBI, ICH, and ischemic stroke)
    • Diffuse cerebral edema
    • Intracranial lesion causing mass effect
  • Options
    • External ventricular drain ^[16]
      • Can be inserted at the bedside or in the operating room by a neurosurgeon or other trained clinician
      • Drainage of 1–2 mL of CSF reduces ICP temporarily. ^[18]
    • Lumbar drain
    • Cerebral shunt
  • Risks: hemorrhage, infection (e.g., ventriculitis, encephalitis, meningitis)
• Decompressive craniectomy (DC): removal of a portion of the skull, which allows the brain to expand in volume, thereby reducing ICP ^[36]
  • Primary DC: removal of a skull flap following evacuation or resection of an intracranial lesion (e.g., brain tumor)
  • Secondary DC: removal of a skull flap without additional surgical procedures to treat refractory elevated ICP
    • Recommended for (controversial): ^[36]
      • Late refractory elevated ICP: reduced mortality, improved outcomes
      • Early or late refractory elevated ICP: improved control of ICP, reduced neuro-ICU length of stay
      • Large hemispheric stroke (e.g., malignant MCA infarction) in patients with an infarct > 12 cm and within 24–48 hours of symptom onset ^[24][37]
    • Not recommended for patients with early refractory elevated ICP
  • Multiple approaches have been described in the literature (suboccipital, subtemporal, frontotemporoparietal, etc.) depending on the type and location of the brain lesion. ^[38]
  • Lowers mortality in TBI without improving neurological or functional outcomes ^[19]

Nonsurgical therapy for refractory intracranial hypertension ^[23]

Controlled hyperventilation

Hyperventilation is primarily used as a temporizing measure for intracranial hypertension refractory to medical therapy. ^[21]

• Indications ^[39]
  • Bridge to surgical therapy for expanding lesions (e.g., intracranial hemorrhages)
  • Treatment of life-threatening elevated ICP pending investigation results and onset of action of medical therapy (e.g., hyperosmolar therapy)
• Therapeutic targets
  • First 30 minutes: PaCO₂ 30–35 mm Hg ^[39]
  • After 30 minutes: normocapnia, i.e., PaCO₂ 35–45 mm Hg (see “Ventilation strategy for elevated ICP”)

Controlled hyperventilation should only be used short-term and is not recommended routinely or for prophylaxis. Avoid excessive hyperventilation (PaCO₂ < 30 mm Hg), prolonged hyperventilation, and hypoventilation of any kind, as CBF and perfusion may become compromised.

Advanced therapies

These are primarily reserved for patients with persistently refractory intracranial hypertension.

• Barbiturate coma: e.g., pentobarbital (off-label, not routinely recommended) ^[18][40][41]
  • Not recommended in patients with large hemispheric stroke ^[24]
  • Adverse effects: e.g., hypotension, hypokalemia, infection, multiorgan dysfunction ^[18]
• Therapeutic hypothermia: highly controversial ^{[14][42][43][44][45][46][47]}
  • No benefit has been observed when used prophylactically ^[14]
  • Not recommended in TBI ^[12][43]

• Irreversible loss of brain function (brain death)

Cerebral edema

• Definition: excess accumulation of fluid within the brain parenchyma as a result of damage to the blood-brain barrier and/or the blood-CSF barrier ^[48]

We list the most important complications. The selection is not exhaustive.