Brain Herniation

Etiology

Multiple factors can predispose to raised intracranial pressure and brain herniation syndrome, including:

• Hematoma (traumatic epidural and subdural hematoma, contusions, intracerebral hemorrhage)
• Missile and non-missile penetrating injuries
• Diffuse subarachnoid hemorrhage
• Pneumocephalus (traumatic or postoperative)
• Malignant infarction
• Tumors
• Infections (abscess, empyema, hydatid cyst)
• Hydrocephalus
• CSF overdrainage
• Fulminant hepatic failure with cerebral edema
• Open spinal dysraphism (intracranial hypotension after spinal CSF leak) [3][4][5][6]

Epidemiology

Traumatic brain injury (TBI) is the predominant cause of death after traumatic injury. Raised intracranial pressure (ICP) especially correlates with poor TBI outcomes.[7]

Pathophysiology

The pathogenesis of brain herniation is based on the Monro-Kellie doctrine, which governs intracranial dynamics and pressure.[8][9][10]

Evolution of Monro-Kellie Doctrine

Alexander Monro Secundus and his student, George Kellie, proposed that the volume of blood circulating in the cranium remains constant. Consequently, expulsion of an equivalent volume of blood from the skull must occur whenever any additional fluid enters the intracranial space. John Abercrombie further advanced this concept by asserting that cranial depression compresses brain parenchyma and diminishes cerebral blood flow, helping disseminate the doctrine within the medical community. At that time, knowledge of CSF and its function was lacking, preventing the completion of the theory. François Magendie later identified CSF as a third intracranial component.

George Burrows challenged the assumption of a perfectly spherical skull and fixed intracranial blood volume, reformulating the doctrine to state that brain tissue, blood, and CSF occupy interdependent volumes within the cranium. When compensatory thresholds fail, and displacement of these components cannot offset added volume, pathological processes ensue. Burrows also introduced intracranial pressure into the analysis of cranial dynamics. Subsequently, Henri Duret, Ernst von Bergmann, and Theodor Kocher demonstrated that CSF displacement into the spinal canal and vascular compression maintain intracranial pressure, while failed compensation produces ischemia and brain shift syndromes. Harvey Cushing later validated and clinically demonstrated the doctrine’s physiological principles.[8]

ICP Waveforms

Burrows first noticed pulsations within the meninges during the arterial systolic phase and during respiratory movements. Angelo Mosso first described the tricuspid variability of the cerebral blood pulse. The ICP pulse waveform is classically characterized by 3 components: P1 (percussion wave), P2 (tidal wave), and P3 (dicrotic wave), with a rising P2 suggesting reduced compliance.[8] 

When the CSF and venous spaces become exhausted, the brain is compressed, generating a steeply rising ICP and increased brain swelling. This concept explains the exponential pressure-volume relationship of the intracranial system (elastance curve).[11] Acute intraoperative brain swelling/herniation reflects loss of compliance and pathological pressure gradients; cerebral perfusion pressure (CPP) may deteriorate as a consequence.[12] The Pressure Reactivity Index (PRx) is pivotal in governing cerebral autoregulation and compensatory reserve.[13] Cerebrovascular autoregulation, the glymphatic system, and cerebral compensatory reserve are major determinants governing ICP dynamics. Therefore, newer insights into the role of cisternal drainage, assessment of changes in ICP pulse morphology, and multimodality neuro-monitoring to determine brain compliance have been adopted in the management of intracranial compartment syndrome.”[9]

Patterns of Brain Herniation

Plum and Posner described the cephalocaudal sequential progression of the brain during herniation.[14] Brain herniation is classified as follows:

• Subfalcine herniation
• Transalar (transsphenoidal) herniation
• Uncal herniation
• Central (trans-tentorial) herniation (descending and ascending)
• Cerebellar tonsillar herniation
• Transcalvarial herniation

Subfalcine herniation

In subfalcine herniation, the ipsilateral cingulate gyrus gets migrated beneath the anterior falx, potentially causing anterior cerebral artery compression and infarction in its distal territory.[15]

Transalar (transsphenoidal) herniation

In the posterior (descending) variant of transalar herniation, infarction may occur within the middle cerebral artery territory, resulting from its compression within the sphenoid ridge. In anterior (ascending) transalar herniation, compression of the supraclinoid segment of the internal carotid artery against the anterior clinoid process leads to infarction within the territory of the anterior and middle cerebral arteries.

Uncal herniation

Transtentorial uncal herniation compresses the oculomotor nerve (CN III) against the tentorial edge, classically producing an ipsilateral dilated, poorly reactive pupil; a transient early constriction (Hutchinson pupil) may rarely precede dilation.[16][17]

Infarction may occur within the temporal or occipital lobe owing to compression of the calcarine branch of the posterior cerebral artery as well. Brainstem and tectal distortion may contribute to aqueductal obstruction and hydrocephalus in severe cases. Significant midline shift and transtentorial brain displacement may distort or compress the third ventricle and cerebral aqueduct, contributing to obstructive hydrocephalus in severe cases. As the midbrain is further displaced, sometimes the contralateral cerebral peduncle is forced against the tentorium edge, creating the Kernohan notch and damaging the contralateral corticospinal tract, thereby resulting in paresis or paralysis ipsilateral to the mass lesion.

Transtentorial central herniation (descending and ascending)

As the pathological descent of the brainstem through the incisura progresses, venous congestion, along with stretching and tearing of small perforators, creates Duret hemorrhages.[18] Clinically, progression from abnormal flexor posturing to abnormal extensor response occurs through the involvement of the rubrospinal and the vestibulospinal tracts. Progression leads to worsening brainstem dysfunction with respiratory and cardiovascular collapse; in extreme, terminal cases, continued downward shift may be accompanied by tonsillar herniation with medullary compression and death. Patients may exhibit characteristic triple components of Cushing triad, consisting of hypertension, bradycardia, and irregular respirations.

Ascending transtentorial herniation can compress the posterior cerebral or superior cerebellar arteries against the tentorium and can follow posterior fossa mass lesions, endoscopic third ventriculostomy, or excessive supratentorial CSF drainage, eg, following an external ventricular drainage.[19][20][21] 

Cerebellar tonsillar herniation

Increased pressure in the posterior fossa forces the cerebellar tonsils through the foramen magnum. These forces will compress the lower part of the brain stem and upper cervical cord, resulting in life-threatening consequences. Compression usually occurs along with ascending or descending transtentorial herniation. Acute herniation can compress the posterior inferior cerebellar arteries, vertebral arteries, and their branches, or the origin of the anterior spinal artery, leading to ischemia of the brainstem, tonsils, and lower cerebellum. Severely elevated ICP (often >40–50 mm Hg), particularly when approaching or exceeding mean arterial pressure, can cause critically reduced CPP, global cerebral ischemia, and progression to brain death.[11] 

Transcalvarial herniation

In cases of calvarial defects, eg, after decompressive hemicraniectomy, edematous brain tissue may herniate outward through the defect along the path of least resistance due to pressure gradients. This external herniation can compress cortical vessels against the bony margins, predisposing to venous congestion and hemorrhagic infarction.

 Other patterns of brain herniation:

• Paradoxical herniation and shrunken skin flap syndrome [22]
• Rare herniations into the arachnoid granulation, the transverse sinus, or the cuneus gyrus [23][24][25]

History and Physical

Rigorous neurological evaluation remains essential when assessing patients at risk for brain herniation, as deterioration may develop unexpectedly.[26] Early recognition of pupillary asymmetry and prompt correction of the underlying cause help to minimize secondary injury and improve outcomes.[27] As herniation syndromes evolve, characteristic neurological signs and symptoms emerge that reflect the pattern and progression of tissue displacement.

Subfalcine herniation produces lower limb weakness resulting from infarction of the corresponding motor homunculus after compression of the pericallosal and callosomarginal vessels. Uncal herniation classically presents with ipsilateral anisocoria and contralateral motor weakness, although the Kernohan–Woltman notch phenomenon may produce ipsilateral weakness. Abnormal posturing signals rostrocaudal deterioration: lesions at the diencephalon or above the red nucleus typically produce abnormal flexor (decorticate) posturing, whereas progression to involvement at or below the red nucleus in the midbrain or upper pons produces extensor (decerebrate) posturing.

Progressive intracranial hypertension with midline shift and downward diencephalic displacement alters sensorium through distortion of ascending arousal pathways and may obstruct the foramen of Monro or cerebral aqueduct, leading to hydrocephalus. The onset of downward transtentorial herniation is characterized by decorticate and decerebrate posturing, along with loss of brainstem reflexes. Respiratory patterns may become progressively abnormal. For example, Cheyne–Stokes, central neurogenic hyperventilation, ataxic breathing, potentially progressing to apnea with advanced brainstem failure. Upward transtentorial herniation may produce dorsal midbrain (Parinaud) features, while hypothalamic–pituitary dysfunction remains uncommon but possible in severe cases.

Evaluation

Vigilant neurological monitoring with the Glasgow Coma Scale (GCS) and pupillary assessment is the key to the evaluation of patients with brain herniation. When available, multimodality monitoring complements clinical examination and imaging by providing continuous, physiology-based markers of cerebral oxygenation, perfusion, autoregulation, and metabolism, helping clinicians detect evolving secondary injury early and individualize targets beyond ICP and CPP alone (see Table 1).

Table 1. Multimodality Monitoring

An automatic pupillometer can aid early detection of pupillary changes suggesting an ICP crisis or impending herniation, facilitating timely escalation and intervention.[28]

Radiological imaging also reveals the following characteristic markers associated with each herniation subtype:

• An effacement of the ipsilateral lateral horn with a displacement of the septum pellucidum in subfalcine herniation occurs, which is followed by progressive compression and obliteration of the basal cisterns along with hydrocephalus resulting from brain torsion (see Images. Hemispheric Infarction Radiologic Findings and Hemorrhagic Transformation  Radiologic Finding).
• As a supratentorial mass expands, the ipsilateral temporal lobe uncus is displaced medially and downward through the tentorial notch. This causes the midbrain to shift away from the mass, compressing the contralateral cerebellopontine cistern between the midbrain and the petrous bone, resulting in its obliteration. Simultaneously, the ipsilateral cerebellopontine cistern is stretched and widened as the midbrain shifts toward the contralateral side, increasing the space on the side of the lesion. Thus, the uncal herniation causes widening of the ipsilateral cerebellopontine cisterns with the obliteration of the contralateral cerebellopontine cisterns. 
• Central (descending) herniation is suggested by effacement of the perimesencephalic cisterns with downward displacement of the diencephalon/midbrain; duret hemorrhages may be present.
• The upward herniation variant leads to flattened quadrigeminal cisterns, "spinning top" appearance of the midbrain, and associated hydrocephalus.[29][30] 

The imaging will also reveal characteristic infarction along with the vascular territory of compressed vessels. In severe diffuse cerebral edema with hypoxic–ischemic injury, a "white cerebellar sign" may be observed.

Cerebral autoregulation may become disrupted, rendering cerebral blood flow increasingly pressure-passive. As intracranial compliance diminishes and compensatory reserve is exhausted, ICP monitoring may reveal characteristic pathological wave patterns. Lundberg A (plateau) waves are abrupt, sustained ICP elevations (often 40–60 mm Hg) lasting 5 to 30 minutes, reflecting severely reduced intracranial compliance and an autoregulatory vasodilatory cascade. Lundberg B waves are lower-amplitude rhythmic oscillations occurring every 0.5 to 2 minutes, commonly seen in hydrocephalus and moderate compliance impairment, and may precede ICP decompensation. The ICP pulse waveform itself has 3 peaks: P1 (percussion), P2 (tidal), and P3 (dicrotic). With worsening compliance, P2 rises relative to P1, and the waveform becomes progressively rounded as individual peaks become indistinct.

Some institutions use the term "brain code" to denote suspected impending herniation or refractory intracranial hypertension requiring immediate escalation of care.[3] The following 10 time-critical red flags of ICP crisis or suspected herniation should trigger immediate escalation:

• New dilated and nonreactive pupil
• New asymmetric pupils or rapidly worsening anisocoria
• Progressive decline in neurological status, especially a drop in GCS by more than 2 points, not explained by nonneurological causes
• Motor exam showing extensor (decerebrate) posturing
• New abnormal posturing (decorticate or decerebrate), especially if worsening
• Cushing reflex (hypertension with bradycardia, often with irregular respirations)
• New irregular respirations, ataxic breathing, or apnea suggestive of brainstem involvement
• Sustained intracranial hypertension on monitoring despite initial measures (for example, ICP above commonly treated thresholds, eg, >22 mm Hg in adults)
• Sudden neurological deterioration during transport, repositioning, suctioning, or intubation
• Seizure with failure to return to baseline consciousness or suspicion of ongoing nonconvulsive seizure with worsening exam

Treatment / Management

Prehospital care during transport and effective emergency management of patients with traumatic brain injury are critical in preventing secondary damage (hypoxia, hypotension, seizure) to the brain resulting from the primary insult.[31][32](B2)

General Measures

The following general protocol is recommended for patients presenting with traumatic brain injury:

1. Call for help and treat this as an ICP crisis. Escalate to a senior clinician, neurosurgery, and prepare for urgent imaging and definitive intervention.
2. Position the patient to optimize for venous outflow. Elevate the head of the bed to greater than 30 degrees and keep the head midline; avoid neck obstruction (tight collars, tube ties, extreme rotation).
3. Minimize noxious stimuli. Control pain, agitation, coughing, and ventilator dyssynchrony with adequate analgesia and sedation.
4. Oxygenation: prevent hypoxemia (target SpO2 ≥94% and restore oxygenation immediately after airway interventions).
5. Provide airway protection and mechanical ventilation as needed for patients with severe TBI. Consider neuromuscular blockade in selected cases of refractory agitation or ventilator dyssynchrony contributing to intracranial hypertension. Use sedatives to calm the patient.
6. Hyperventilation may be used briefly as a temporizing measure for impending herniation (target PaCO₂ about 30–35 mm Hg) while definitive treatment is arranged; prophylactic hyperventilation should be avoided, particularly in the first 24 hours after injury.
7. Maintain euvolemia and avoid hypotension; avoid hypotonic fluids.
8. Administer osmotherapy, eg, mannitol, to lower ICP.
9. Control blood pressure while ensuring adequate perfusion of the brain.
10. Consider corticosteroids to reduce vasogenic edema in patients with malignancies and abscesses.
11. Target normothermia and avoid or correct hyponatremia (both worsen cerebral edema and ICP dynamics).
12. If a CSF drain is present, ensure it is functioning and use CSF diversion (EVD drainage) as part of first-line ICP control. Continue urgent assessment to identify underlying etiologies requiring surgery or other definitive treatment.

Physiologic Targets

In patients with severe TBI, intracranial hypertension, or risk of herniation, the following clearly defined physiologic targets guide management:

• Oxygenation:
  • SpO₂ ≥94% (initial target)
  • Avoid hypoxia (SpO₂ <90% or PaO₂ <60 mm Hg is associated with worse outcomes)
• Ventilation
  • Normocapnia: PaCO₂ approximately 35–40 mm Hg (or ETCO2 ~35–40 mm Hg) 
  • If impending herniation: brief temporizing hyperventilation to PaCO₂ approximately 30–35 mm Hg while definitive therapy is arranged 
• Blood pressure/perfusion
  • Avoid hypotension; support systemic pressure to maintain cerebral perfusion. 
  • CPP target 60–70 mm Hg (individualize to autoregulation status; avoid aggressive CPP >70 with fluids/pressors) 
• ICP
  • Treat sustained ICP elevation >22 mm Hg (commonly used initial treatment threshold) 
  • When weighing higher-risk escalation, consider a practical treatment range of 20–25 mm Hg. 
• Temperature
  • Target normothermia; treat hyperthermia 
• Sodium/osmolality
  • Avoid and correct hyponatremia (Na <135 mEq/L)
  • During hyperosmolar therapy: monitor sodium/osmolality closely; do not treat “to exceed” a serum osmolality threshold (use limits per local protocol rather than targets)

Brain Trauma Foundation guidelines recommend monitoring ICP in patients with severe TBI (ie, GCS of 3 to 8) and have either (1) abnormalities in CT of the head or (2) meet at least 2 of the following 3 criteria: age over 40 years; systolic blood pressure under 90 mm Hg, or abnormal posturing. The genesis of this approach is that ICP elevation may precede clinical deterioration, supporting early monitoring in selected severe TBI patients.[7] However, studies on ICP-guided rescue therapy have produced mixed results. Level I evidence for any strategies targeted for managing refractory intracranial hypertension remains lacking. Trials of ICP-guided management and decompressive craniectomy show mixed effects on functional outcomes; decompressive craniectomy reduces ICP and can improve survival in selected refractory cases, with important disability trade-offs (DECRA, RESCUEicp). Thresholds for ICP and CPP guided therapies are 22 mm Hg and 60 to 70 mm Hg, respectively.

Proposed tiers in the management of refractory intracranial hypertension and resultant brain herniation (see Table 2) include:

1. Evacuation of mass lesions (hematoma, contusion, infarction, edema, tumors)
2. Physiological neuroprotection
3. Sedation (intravenous with early reversibility, midazolam, fentanyl), analgesics, and ventilation
4. CSF drainage through external ventricular drain (EVD). External lumbar drainage (ELD) may be considered only in carefully selected patients (with appropriate imaging and without obstructive hydrocephalus or significant mass effect) and with close monitoring.
5. Osmotherapy-Urea was used in the 1950s, mannitol (20%) in the 1960s, and hypertonic saline (3%/7.5%/10%/23.4%) in the 1990s. Mannitol and sodium (hypertonic saline) both have high reflection coefficients (σ ≈ 0.9), meaning they are largely excluded from crossing the blood-brain barrier and thus efficiently draw water from the brain parenchyma into the intravascular space, provided the blood-brain barrier is intact.[11]
6. Hyperventilation (drives off CO₂, thereby causing cerebral vasconstriction)
7. Hypothermia (reduces cerebral metabolism)
8. Barbiturate coma (burst suppression)
9. Decompressive hemicraniectomy [3][33]

Table 2. Refractory Intracranial Hypertension Management Tiers

 The Brain Trauma Foundation Level IIA recommendations (2020)

The following recommendations are supported by the Brain Trauma Foundation:

• Secondary decompressive craniectomy in the setting of late, refractory ICP elevations is recommended to improve mortality and favorable outcomes (based on results of RESCUEicp).
• Secondary decompressive craniectomy for early refractory ICP elevation is not recommended to improve mortality and favorable outcomes (based on results of DECRA).
• Secondary decompressive craniectomy, whether early or late, likely reduces ICP and ICU length of stay; however, its impact on functional outcomes remains unclear.
• Craniotomy is a good option versus decompressive craniectomy for ASDH in patients without brain swelling (RESCUE-ASDH trial)
• A large frontotemporoparietal decompressive craniectomy (12–15 cm in diameter) is recommended.[34]

Differential Diagnosis

Certain clinical entities can mimic brain herniation syndrome owing to rapid clinical and neurological deterioration in patients, including:

• Posttraumatic subclinical seizures
• Postictal state and nonconvulsive status epilepticus
• Medication or sedation effects (eg, opioids, benzodiazepines, and propofol) causing pupillary and consciousness changes
• Metabolic causes that mimic brainstem dysfunction (hypoglycemia, hypercapnia, severe hyponatremia)
• Paroxysmal sympathetic hyperactivity (formerly termed paroxysmal autonomic instability with dystonia)
• Acute hydrocephalus
• Tension pneumocephalus
• Dyselectroytemia 
• Meningitis
• CSF over-drainage syndrome
• Ocular causes of anisocoria (topical anticholinergics, Adie pupil, prior eye surgery)
• Osteopetrosis
• Costello and posterior fossa crowding syndrome

Pertinent Studies and Ongoing Trials

Randomized trials demonstrate that decompressive craniectomy lowers mortality in refractory traumatic intracranial hypertension; however, this survival benefit often shifts outcome distribution toward survival with severe disability in a subset of patients. Outcomes vary according to timing and indication, with differences observed between early “neuroprotective” decompressive craniectomy and last-tier rescue decompressive craniectomy.[35]

Associations among ICP magnitude, cumulative burden, and outcome indicate that lower ICP generally correlates with improved prognosis, yet no single narrow optimal ICP range applies to all patients. Sustained ICP >22 mm Hg commonly prompts treatment, with targets individualized according to overall physiology and, when available, autoregulation status.[36][37] Evidence remains mixed. A randomized controlled trial comparing an ICP monitor–driven protocol with examination and CT-guided management failed to demonstrate superiority of the ICP-monitor strategy in that context, whereas observational studies and guideline syntheses suggest potential short-term mortality reduction in selected severe TBI populations.[7] Although ICP monitoring is a central tenet of many management algorithms, reliance on numeric thresholds may trigger interventions that inadvertently cause harm.

Recent research on intracranial hypertension management explores enhancing glymphatic “cooling and clearing” pathways through modulation of sleep patterns and targeting aquaporin channels, alongside strategies to attenuate catecholamine hyperactivity (glutamate storm).[9][38][39]

Prognosis

Prognosis in brain herniation and severe TBI depends on multiple variables, including duration of herniation, patient age, presenting GCS, presence of anisocoria, associated polytrauma, concurrent hypoxia and hypotension, lesion type such as extradural versus subdural hemorrhage, Marshall and Rotterdam CT scores, and ICP measurements. The advancing progression of a herniation syndrome correlates with an increasingly poor likelihood of recovery.[40][41][42]

The following factors affect prognosis:

• Increasing age is associated with an unfavorable outcome (centered at 40 years).[43][44]
• GCS score at admission is highly predictive of clinical outcomes.[45][46]
• Pupillary asymmetry is associated with an unfavorable prognosis.[47]
• Marshall and Rotterdam scores have high accuracy in predicting mortality in patients with acute and severe traumatic brain injury.[48][49]
• Hypoxia is an independent risk variable for poor prognosis in head injury.[50][51] Patients with prehospital saturation ≥94% had better outcomes among hypotensive patients with TBI.[52][53]
• Concurrent hypotension in TBI confers nearly 2-fold increased odds of mortality.[54]
• TBI is the most prevalent cause of death in polytrauma patients.[55] Mortality rates are higher in patients with TBI associated with polytrauma (35%) compared to those with isolated traumatic brain injury (24%).[56]
• Both hypertonic saline and mannitol reduce ICP; comparative superiority is inconsistent across studies, with several analyses suggesting hypertonic saline may provide more sustained ICP reduction.[57][58]
• EVD can control intracranial pressure and avoid third-tier therapeutic measures (therapeutic hypothermia, decompressive craniectomy, and barbiturate coma) or avoid a decision to withdraw life-sustaining treatment in almost 40% of cases.[59] ELD can be effective in carefully selected patients with close clinical and radiological vigilance to avoid precipitating herniation ("coning").[60] Meta-analysis has proven the benefits of lumbar drainage in ICP reduction, with complication rates similar to those of EVD therapy. However, clinical and radiological vigilance is needed to recognize coning early.[61]
• Early surgical evacuation of a hematoma within 6 hours of brain herniation can significantly reduce mortality and improve survival, especially in cases of cerebellar hemorrhage and traumatic subdural hematoma, but its effect on neurological recovery and long-term prognosis is less certain and depends on patient selection, hematoma characteristics, and surgical technique.[62]
• ICP-guided therapy has also been shown to reduce mortality and hospital length of stay.[63] Care focused on maintaining monitored intracranial pressure at 20 mm Hg or less has not been observed to be superior to a care bundle approach based on imaging and clinical examination.[64]

Complications

Brain herniation can progress from a subtle finding of pupillary asymmetry (uncal herniation) to an altered level of consciousness (compression of the reticular activating system), then progress to the moribund stage of abnormal posturing (dysfunction of the diencephalon and the brainstem), and finally death resulting from respiratory arrest (brainstem failure).

An associated infarction is seen along with the vascular territory of the compressed vessels associated with each herniation subtype. In advanced global hypoxic–ischemic injury with diffuse cerebral edema, noncontrast CT may show a "white cerebellum" (reversal) sign.[65]

Complications of Brain Herniation

Complications of brain herniation include:

• Cerebral infarction 
• Seizure
• Coagulopathy
• Dyselectrolytemia
• Neurogenic pulmonary edema 
• Dysautonomia
• Panhypopituitarism 
• ICU-related complications (eg, critical illness neuropathy, pneumonia, sepsis, deep vein thrombosis, pressure ulcers)
• Chronic dependency
• Superficial siderosis
• Taupathies
• Persistent vegetative state
• Brainstem death
• Brain death [30][66][67][68]

Complications Relating to Management Strategies (Tiers)

Treatment-related complications include:

• EVD is associated with ventriculitis, track hematomas, mechanical failure, upward transtentorial herniation (rarely) in the setting of posterior fossa lesions/compartmental pressure gradients, inadvertent pull, misplacements, and critical cerebrospinal fluid hypovolemia.[69]
• Lumbar CSF drain is associated with similar complications to EVD, including inadvert brain coning.
• Postoperative hematoma is associated with recurrence and delayed traumatic intracranial hematoma.[26] 
• Complications of craniectomy include reperfusion syndrome (hemorrhagic transformation), ventriculomegaly with or without hydrocephalus, and shrunken flap (trephination) syndrome.[70][71]
• Mannitol can cause acute renal failure. Hypertonic saline can cause hypernatremia, hyperchloremia/metabolic acidosis, and volume overload; rapid osmolar shifts may precipitate neurological complications, and cause skin sloughing if it extravasates into the subcutaneous tissues (higher concentrations and/or prolonged infusions may warrant central access per institutional protocol), and can cause rebound intracranial hypertension.[11] Mannitol, particularly with repeated dosing and brain-blood barrier disruption, has been associated with a reverse osmotic shift and rebound cerebral edema; both agents require careful laboratory and hemodynamic monitoring. Mannitol and hypertonic saline can cause a rebound increase in ICP owing to propagation of “idiogenic osmoles” (polyols, amino acids, and methylamines) via astrocytes.[11]
• Hyperventilation can lead to cerebral ischemia from reduced cerebral blood flow; abrupt normalization of PaCO₂ may be followed by a rebound increase in ICP.
• Hypothermia is associated with arrhythmias, immunosuppression, and coagulation disorders.[72]
• Barbiturate coma is associated with hypotension, immunosuppression, and critical illness-related polyneuromyopathy.[73][74]