Management of intracranial hypertension with and without invasive intracranial pressure monitoring

Table 1 Usual indications for intracranial pressure monitoring

Indication	Likelihood of ICH
Overt signs of intracranial hypertension	Very high
Herniation syndromes (specially anisocoria)
Cushing's triad
Comment (1): These cases are usually identified upon presentation and usually undergo surgical treatment followed by ICP monitoring, except for diffuse brain edema, where isolated ICP monitoring may be indicated; Comment (2): During the ICU stay, this may present as a neuroworsening scenario that prompts treatment escalation, sometimes regardless of ICP monitoring
High risk of intracranial hypertension with unreliable neurological examination	High (approximately 50%)
Coma (i.e., GCS ≤ 8) with abnormal head CT scans (cistern compression, midline shift, contusions, hematomas)
Comment (1): These cases usually don't have overt signs of intracranial hypertension. Coma may be a manifestation of intracranial hypertension or not, but monitoring is advised both to diagnose elevated ICP and eventually to guide treatment. Monitoring may be beneficial both to avoid overtreatment and undertreatment; Comment (2): In scenarios where ICP monitoring is unavailable, these patients represent the greatest challenge to address treatment escalation and de-escalation
Low risk of intracranial hypertension	Low (approximately 10%-15%)
Coma (i.e., GCS ≤ 8) with normal head CT scans
Comment: These cases are unlikely to benefit from ICP monitoring. Repeat CT scans, frequent neurological examinations and noninvasive strategies may help identify the few patients who develop intracranial hypertension

CT: Computed tomography; ICP: Invasive intracranial pressure; GCS: Glasgow Coma scale; ICH: Intracranial hemorrhage.

Table 2 Studies comparing invasive intracranial pressure monitoring vs no invasive intracranial pressure monitoring from 2020 to 2024

Ref.	Country	Design, sample size	Population	Findings
Al Saiegh et al[88]	United States	Retrospective cohort, n = 36929	TBI	ICP monitored patients had a 25% reduction of in-hospital mortality compared to non-ICP monitored patients[79]
Che et al[89]	China	Retrospective cohort, n = 116	ICH	No difference in mortality; ICP monitoring predicted of 6-month favorable outcome (OR: 17, 95%CI: 3-95, P = 0.001)[80]
Ren et al[90]	China	Retrospective cohort, n = 196	ICH	ICP monitoring group presented higher rate of favorable GOS-E at six-months (OR: 0.54, 95%CI: 0.31-0.93, P = 0.027)
Li et al[91]	China	Retrospective cohort, n = 91	Moderate TBI	No difference in 6-month GOS or mortality between the groups
Robba et al[44]	42 countries, mostly in Europe	Prospective cohort, n = 2395	1287 TBI; 587 ICH; 521 SAH	ICP monitoring group with lower 6-month mortality (34% vs 49%, P < 0.0001)
Menacho et al[92]	United States	Retrospective cohort, n = 494	ICH	ICP monitor placement was associated with poor outcome (OR: 2.76, 95%CI: 1.30-5.85, P = 0.008), but not with death (P = 0.652)
Dallagiacoma et al[93]	42 countries, mostly in Europe	Prospective cohort, n = 587	ICH	ICP monitoring is associated with reduction of 6-month mortality (HR: 0.49, 95%CI: 0.35-0.71; P = 0.001)
Foote et al[94]	United States	Retrospective cohort, n = 123	Severe TBI	ICP monitored patients had longer length of hospital stay (12 vs 3, P < 0.001)
Yang et al[47]	China	Prospective cohort, n = 2029	Severe TBI	ICP monitoring patients had lower in-hospital mortality (19.82% vs 26.83%, P < 0.001)
Nattino et al[52]	7 countries in Europe	Prospective cohort, n = 1448	TBI	Worse 6-month GOS-E for ICP monitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, P = 0.005)
Shibahashi et al[48]	Japan	Retrospective cohort, n = 31660	Severe TBI	ICP monitoring associated with lower in-hospital mortality (31,9% vs 39.1%, P < 0.001) and no difference in patients with unfavorable outcomes at discharge (80.3% vs 77.8%, P = 0.127)
Lee et al[95]	Korea	Retrospective cohort, n = 912	TBI	No difference in in-hospital mortality (62% vs 58.9%, P = 0.59) or favorable outcome (25.3% vs 24.6%, P = 0.88)
Waack et al[96]	United States	Retrospective cohort, n = 1664	TBI	ICP monitoring associated with less mortality (35.1% vs 42.4%, P < 0.01) and discharge home (7.9%, 19.3%, P < 0.001)

TBI: Traumatic brain injury; ICH: Intracranial hemorrhage; SAH: Subarachnoid hemorrhage; ICP: Intracranial pressure.

Table 3 Concepts that need to be considered for the interpretation of neutral and divergent results regarding intracranial pressure monitoring benefit

Concept	Interpretation
Selection bias	Some observational studies include participants that would be excluded in a clinical trial (e.g., non salvageable patients) of ICP monitoring. They are less likely to receive ICP monitoring in clinical practice and very much more likely to die or have unfavorable outcomes. Confounding adjustment is not enough to address selection bias when the proposed treatment (or monitoring device) would not have been received in a clinical trial
Confounding	While many studies address confounding at baseline, the use of ICP monitoring may lead to differential treatment intensities, which may vary from place to place. Therefore, modern causal inference methods that properly address time-dependent confounding with G-methods is necessary to address not only treatment thresholds, but the benefits or not of ICP monitoring
Dichotomania	Dichotomization of continuous variables leads to loss of information. While there are thresholds that are associated with increases in mortality, the relationship between high ICP levels and worse outcomes is not linear and certainly not a two-level (higher or lower than 20 or 22 mmHg) relationship. This dichotomization leads to riskier treatments being proposed for patients with intermediate (20-25 mmHg) ICP elevations that may not be as harmful as very high (> 30 mmHg) ICP elevations
Risk-guided management	In Medicine, in general, management is guided by different prognostic risk categories. Riskier therapies should be reserved for high risk scenarios where no other alternatives exist. Using tier 3 therapies (barbiturates, hypothermia, craniectomy) for intermediate risk patients based on dichotomania (ICP threshold) may therefore lead to more harm than benefit. Even among the very high risk patients, it may not be beneficial whatsoever, unless as a bridge to a definitive treatment
Prognostic association vs causal effect	Increased intracranial pressure is essentially the consequence of a severe acute brain injury, whether traumatic or not, and is a potential mediator of worse outcomes. Its prognostic association with worse outcomes is well documented. However, whether high ICP has a causal effect on increased mortality or disability is likely dependent on the non-linear relationship of high ICP with worse outcomes. At very high ICP levels (i.e., > 30 mmHg), this is very likely true and high ICP likely mediates this relationship. However, at intermediate high ICP levels (20-30 mmHg), it's likely that there is a complex interplay between treatment intensity, underlying cause of high ICP (diffuse axonal injury, cerebral edema, contusions, etc.), physiological compensation (e.g., maintenance or not of cerebral flow autoregulation) and ICU-acquired complications potentially caused by treatment intensity. Hence, we cannot assume that treatment escalation above proposed ICP thresholds is always beneficial with the current evidence base

ICP: Intracranial pressure; ICU: Intensive care unit.

Table 4 Criteria for suspected intracranial hypertension from the CREVICE protocol

Major criteria (one criteria should indicate SICH treatment)

CT classification of Marshall III or worse

Compressed cisterns (Marshall diffuse injury III)

Midline shift > 5 mm (Marshall diffuse injury IV)

Non-evacuated mass lesion > 25 cc

Minor criteria (at least two should be observed to indicate SICH treatment)

Glasgow coma scale (motor) ≤ 4

Pupillary asymmetry

Abnormal pupillary reactivity

Marshall diffuse injury II

CT: Computed tomography; SICH: Suspected intracranial hypertension.

Table 5 Treatments that are not recommended for patients with severe traumatic brain injury

Mannitol by non-bolus continuous intravenous infusion
Scheduled infusion of hyperosmolar therapy
Lumbar cerebrospinal fluid drainage
Furosemide
Routine use of steroids
Routine use of therapeutic hypothermia to temperatures below 35 ℃
High-dose propofol to achieve burst suppression
Routinely decreasing PaCO2 below 30 mmHg
Routinely raising cerebral perfusion pressure above 90 mmHg

Table 6 Neuroworsening definition

Spontaneous decrease in the GCS motor score ≥ 1 points

New decrease in pupillary reactivity

New pupillary asymmetry or bilateral mydriasis

New focal motor deficit

Herniation syndrome or Cushing's triad requiring immediate physician response

GCS: Glasgow Coma scale.

Table 7 Tiers of therapy for intracranial hypertension

Tier 0: Basic neurocritical care management for ventilated patients at risk of intracranial hypertension

ICU admission with proper monitoring, including: (1) Invasive arterial pressure monitoring; (2) End-tidal CO2 monitoring; and (3) Core temperature measurement

Venous return optimization with: (1) Head-of-bed elevation to 30-45 ℃; (2) Midline head positioning; and (3) Avoidance of tight cervical collars when possible

Avoidance of ICP spikes with: (1) Analgesia and (2) Mild sedation (not ICP directed) to prevent pain, agitation and ventilator asynchrony

Avoidance of secondary insults, including:

(1) Hypoxemia: Target SpO2 94%-98%

(2) Hypotension: Avoid hypotension by targeting a minimal systolic arterial pressure of 100-110 mmHg or to CPP 60-70 mmHg

(3) Hypocapnia: Target PaCO2 to normal levels (35-40 mmHg)

(4) Hyponatremia: Target serum Na+ to 140-145 mmol/L

(5) Hyperthermia: Target core temperature to below 38 ℃

(6) Hypoglycemia: Target glucose levels to 110-180 mg/dL

Avoid anemia (i.e., Hb < 7.0 g/dL)

Consider anti-seizure prophylaxis for up to 1 week

Tier 1: Deep sedation, CPP optimization, EVD drainage and hyperosmolar therapy

Revise Tier 0 treatment:

(1) Target CPP of 60-70 mmHg or MAP 80-90 mmHg in absence of invasive ICP monitoring

(2) Maintain PaCO2 at lower end of normal (35-38 mmHg)

Intermittent bolus hyperosmolar treatment: (1) Hypertonic saline; and (2) Mannitol

Increase sedation beyond mild sedation to lower ICP (if measured) or to a target RASS of -4/-5 (if ICP not measured), but not to target burst-suppression

Cerebrospinal fluid drainage if external ventricular drain in situ or consider the placement of an EVD

Consider EEG monitoring (if available)

Tier 2: Additional measures with controversial effect

Mild hypocapnia in a lower range (32-35 mmHg)

Trial of neuromuscular paralysis (among ICP monitored patients)

If ICP decreases with a bolus, consider a continuous infusion

Trial of hemodynamic augmentation beyond usual CPP targets:

Perform MAP challenge to assess cerebral autoregulation: If ICP decreases with increased MAP, consider sustaining higher MAP, but no more than a CPP greater than 90 mmHg

Avoid any other adjustments during MAP challenges

In patients without ICP monitors, this trial may be considered with TCCD/TCD measurements

Tier 3: Highly efficacious therapies to reduce ICP, but with demonstrated increased risk of complications (i.e., should not be routinely used except under specific circumstances)

Barbiturate coma with pentobarbital or thiopentone to ICP control (if efficacious) or to pupil abnormality correction (when ICP is not measured)

Secondary decompressive craniectomy

Mild hypothermia (35-36 ℃) with active cooling measures

ICP: Intracranial pressure; MAP: Mean arterial pressure; CPP: Cerebral perfusion pressure; TCCD: Transcranial color-coded duplex scan; TCD: Transcranial doppler; EVD: External ventricular drain; ICU: Intensive care unit.

Table 8 Altered findings from non-invasive estimates of intracranial pressure

(1) Optic nerve sheath diameter (ONSD)

ONSD > 6 mm (any side)

Increase in ONSD > 0.5 from baseline value (any side)

(2) Noninvasive TCD/TCCD ICP estimation (nICP)

nICP > 20-22 mmHg (any side)

(3) Pulsatility index (PI)

PI > 1.4 with FVd < 20 cm/s (any side)

Increase in PI > 0.5 from baseline value (any side)

(4) Pupillometer derived neurological pupillary index (NPi)

NPi < 3 (any side)

NPi reduction > 1 from baseline value (any side)

Table 9 Summary of intracranial pressure managing protocols

	ICE protocol	CREVICE protocol	SIBICC protocol	B-ICONIC protocol
Setting	BEST-TRIP study (Latin America, limited resources)	Post-BEST-TRIP refinement (Latin America, limited resources)	High-resource ICU with access to invasive multimodal monitoring	Low-resource settings without access to invasive monitoring
Type of monitoring	Non-invasive ICP monitoring	Non-invasive ICP monitoring	ICP ± brain oxygen monitoring (PbtO2)	Non-invasive ICP monitoring
Trigger for protocol activation	GCS ≤ 8 with abnormal CT scan	Suspected intracranial hypertension (SICH): 1 major or 2 minor criteria (e.g., imaging, age, motor response, hypotension)	Elevated ICP and/or low PbtO2	SICH plus ≥ 2 abnormal non-invasive findings (see below)
Basis for monitoring	Serial clinical exams and CT scans	Clinical exams and CT; revised with definitions of neuroworsening and structured de-escalation	Continuous ICP and/or PbtO2 values with tiered thresholds	Four non-invasive markers: (1) ONSD; (2) pulsatility index (3) estimated ICP via TCD; and (4) NPi on pupillometry
Threshold for escalation	Clinical or radiological neuroworsening	Neuroworsening or failure of Tier 1 therapy	ICP ≥ 22 mmHg, PbtO2 < 20 mmHg, or clinical deterioration	Two or more non-invasive abnormalities, or clinical worsening
Treatment Strategy (Tiers)	Aggressive from outset; includes hyperosmolar therapy, hyperventilation, barbiturates, decompressive craniectomy	Tiered escalation (Tier 1 to Tier 3); last treatment in should be first out	Tiered algorithm with increasing intensity and risk (Tier 1 to 3), individualized per ICP and PbtO2 status	Uses CREVICE framework with adapted triggers; relies on availability of non-invasive modalities
De-escalation guidance	Not clearly structured; based on improvement or repeat imaging	Defined matrix combining imaging and neuro exam (pupils, motor score); last treatment added is first to be withdrawn	Heatmap and structured matrix based on ICP/PbtO2; includes neuroworsening and “tier zero” baseline care	Structured de-escalation using improvement of non-invasive markers and clinical status
Limitations	Aggressive, CT-dependent, lacks flexibility for mild cases	Still CT-dependent; subjective criteria for SICH; limited data validation	Based on expert consensus (Delphi method), lacks RCT validation	Dependent on accuracy of non-invasive markers; potential for false-positives or over-treatment
Unique features	First consensus protocol for ICP-unmonitored patients; used in RCT	Adds clarity on neuroworsening, introduces structured de-escalation	Integrates ICP and brain oxygenation; includes “MAP challenge” and not recommended interventions list	First consensus using only non-invasive data; bridges evidence gap in LMICs

CT: Computed tomography; GCS: Glasgow Coma scale; ICP: Intracranial pressure; LMICs: Low- and middle-income countries; MAP: Mean arterial pressure; NPi: Neurological pupil index; ONSD: Optic nerve sheath diameter; PbtO₂: Brain tissue oxygen pressure; RCT: Randomized controlled trial; SICH: Suspected intracranial hypertension; TCD: Transcranial doppler; ICU: Intensive care unit.