Analytic Review

Journal of Intensive Care Medicine

1-8
Initial Diagnosis and Management of © The Author(s) 2023

Acutely Elevated Intracranial Pressure Article reuse guidelines:

sagepub.com/journals-permissions
DOI: 10.1177/08850666231156589
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Hashim Kareemi, MD1 , Michael Pratte, MD2,

Shane English, MD, MSc3,4, and Ariel Hendin, MD1,3

Abstract
Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet
its initial detection remains difficult because of the variety of manifestations that it can cause disease states it is associated
with. Several treatment guidelines exist for specific disease processes such as trauma or ischemic stroke, but their recom-
mendations may not apply to other causes. In the acute setting, management decisions must often be made before the under-
lying cause is known. In this review, we present an organized, evidence-based approach to the recognition and management of
patients with suspected or confirmed elevated ICP in the first minutes to hours of resuscitation. We explore the utility of
invasive and noninvasive methods of diagnosis, including history, physical examination, imaging, and ICP monitors. We syn-
thesize various guidelines and expert recommendations and identify core management principles including noninvasive
maneuvers, neuroprotective intubation and ventilation strategies, and pharmacologic therapies such as ketamine, lidocaine,
corticosteroids, and the hyperosmolar agents mannitol and hypertonic saline. Although an in-depth discussion of the defin-
itive management of each etiology is beyond the scope of this review, our goal is to provide an empirical approach to these
time-sensitive, critical presentations in their initial stages.

Keywords
intracranial pressure, ICP, traumatic brain injury, TBI, intracranial hypertension, hypertonic saline, mannitol

Introduction Prompt recognition, monitoring, and treatment of raised ICP

Elevated intracranial pressure (ICP) is a common and potentially
life-threatening condition encountered in a wide array of neuro-
logical pathologies. It is associated with increased mortality1,2
and poor neurologic outcomes3,4 in traumatic brain injury
(TBI), and decreased survival in intracerebral hemorrhage5 and
acute ischemic stroke.6 Normal ICP in adults is generally
defined as an ICP between 5 and 15 mm Hg.7 It can be under-
stood fundamentally as an equilibrium in the partial pressures
of fluids, namely, arterial blood, venous blood, and cerebral
spinal fluid, in addition to the largely incompressible brain paren-
chyma within the fixed volume of the cranium, as described by
the Monroe-Kellie Doctrine.8 If the volume of one of these or
additional components (such as a neoplasm) increases, venous
blood and cerebrospinal fluid are displaced out of the cranium
to maintain equilibrium. In a state of elevated ICP, this compen-
satory mechanism may become dysfunctional, and neurologic
injury may result through 2 mechanisms: hypoperfusion/ische-
mia and herniation. Ischemic injury is the result of decreased
cerebral arterial blood flow secondary to insurmountable ICP
and dysregulated vascular compensation.7 Herniation is the
process by which brain parenchyma is displaced from one com-
partment to another (eg, uncal or transtentorial herniation), with
subsequent compression of critical structures such as the
brainstem.
are essential in the management of critical intracranial patholo-
gies including TBI, intracranial infections, malignancies, and
neurovascular emergencies. The Brain Trauma Foundation rec-
ommends treatment of ICP over 22 mm Hg, as this is the thresh-
old for increased mortality.9 In 2020, the Neurocritical Care
Society released guidelines for the treatment of acute cerebral
edema,10 as well as an updated algorithm for intracranial hyper-
tension and herniation as part of their Emergency Neurological
Life Support program.11 However, given that this topic is a
1
Department of Emergency Medicine, The Ottawa Hospital, University of
Ottawa, Ottawa, Ontario, Canada
2
Department of Internal Medicine, University of Ottawa, Ottawa, Ontario,
Canada
3
Department of Medicine (Critical Care), University of Ottawa, Ottawa,
Ontario, Canada
4
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa,
Ontario, Canada
Received October 19, 2022. Received revised January 25, 2023. Accepted
January 26, 2023.
Corresponding Author:
Hashim Kareemi, The Ottawa Hospital, Civic Campus, Department of
Emergency Medicine, 1053 Carling Avenue, Ottawa, Ontario, Canada.
Email: hkareemi@toh.ca
2 Journal of Intensive Care Medicine 0(0)
rapidly evolving area of research, many of these suggestions are
generalized and lack practical guidance that may be easily
employed in patient care. Particularly, in acute resuscitation
of patients with unknown etiology or degree of elevated ICP,
delays or errors in treatment can have deleterious consequences.
This review presents a pragmatic approach to the initial man-
agement of a patient with elevated ICP, with a focus on early rec-
ognition in the first minutes to hours of resuscitation. The
recommendations made herein combine current evidence with
expert consensus to provide empiric treatment for the undifferen-
tiated patient with raised ICP, such as those presenting in the emer-
gency department. A disease-specific approach or advanced
therapeutic strategies implemented outside of this hyperacute
phase are outside of the scope of this review and covered in
various guidelines.9,12–15 There will be particular emphasis on
rapid recognition, noninvasive treatment, pharmacologic therapy,
and practical considerations for neuroprotective intubation.
Diagnosis
History and Physical Examination
As many patients with elevated ICP have altered mental status,
history is often limited and there is equivocal evidence support-
ing its utility. Upon approaching a patient with suspected ele-
vated ICP, one may gather a history of classic signs or
symptoms, including headache, vomiting, and change in
mental status; however, none of these findings are specific.16
Despite this, history may provide important information in
patients whose diagnosis is uncertain to clarify the etiology or
likelihood of high ICP (eg, meningismus, trauma, or use of
anticoagulants).
A recent meta-analysis explored the utility of 3 common phys-
ical examination findings for raised ICP.17 Although no single
finding was diagnostic of the condition, pupillary dilation was
found to be highly specific (85.9%) but not sensitive (28.2%).
In contrast, a Glasgow Coma Scale (GCS) of 8 or below was
quite sensitive (75.8%) but poorly specific (39.9%). There is evi-
dence that the “Cushing triad” of hypertension, bradycardia, and
irregular breathing may have a specificity as high as 96.9%18;
however, it is poorly sensitive.18,19 In extreme situations, uncon-
trolled ICP may lead to cerebral herniation syndromes, resulting
in various findings including cranial nerve deficits and lateraliz-
ing neurological deficits. These are emergent conditions requir-
ing prompt neurosurgical evaluation. In extremis or if left
untreated, patients may develop brain death—the complete and
irreversible loss of all brain function.20 Given the importance
of rapid intervention in elevated ICP, noninvasive management
should be initiated based on convincing clinical history and phys-
ical examination findings and should not be delayed by further
investigations.
Imaging
Computed tomography (CT) is a useful imaging modality for
the evaluation of elevated ICP and should be used to
supplement the history and physical examination when the clin-
ical context permits. Especially, when the etiology is uncertain,
convincing CT scan findings in conjunction with a history and
physical examination may be sufficient to make the diagnosis of
elevated ICP.21 The most sensitive signs for elevated ICP on CT
include basal cistern effacement (85.9%), midline shift (80.9%),
and a Marshall class of at least 3 (80.6%).17 The Marshall clas-
sification is a grading system using key findings on CT neuro-
imaging to prognosticate traumatic brain injuries.22 In addition
to specific signs of elevated ICP, CT may provide diagnostic
clarification on the etiology of elevated ICP, allowing for plan-
ning of definitive management as initial resuscitative steps are
taken. Conversely, magnetic resonance imaging (MRI) is
rarely used in the evaluation of acutely elevated ICP.
Although it has a similar utility as CT for ICP evaluation,
MRI is relatively slow and costly, making it impractical in
emergent situations. Imaging should not delay initial manage-
ment steps in the context of a high pretest probability of ele-
vated ICP. Although CT scans may provide valuable
information and diagnostic clarification, noninvasive manage-
ment should simultaneously be initiated in patients with a mod-
erate probability of elevated ICP while arranging for imaging.
Point-of-Care Ultrasound
As point-of-care ultrasound (POCUS) becomes increasingly
available, several techniques have gained popularity in the iden-
tification of raised ICP. The use of transcranial doppler ultraso-
nography relies on qualitative, noninvasive measurements of
cerebral blood flow via bone windows in the cranium to esti-
mate ICP using flow velocity and various other parameters.23
However, transcranial doppler was shown to have limited
utility with a relatively low area under the receiver operating
characteristic curve (AUROC) (0.55-0.72 for pulsatility index,
0.85 for arterial blood pressure).17 Likewise, another small
study demonstrated pulsatility index to be a poor proxy for
ICP estimate.24
Optic nerve sheath diameter (ONSD) relies on the assump-
tion that increases in ICP will be reflected in the dilatation of
the optic nerve sheath through the communication of the intra-
cranial and intraorbital subarachnoid spaces. Practically, it
involves measuring the diameter of the optic nerve sheath pos-
terior to the orbit with POCUS. Its utility is more encouraging
(AUROC for diagnostic accuracy of 0.94 among 10 studies)17;
however, these studies used different cutoffs for diameter mea-
surements, making comparison difficult. Another recent meta-
analysis found ONSD to be highly sensitive (92%) and specific
(86%) in the diagnosis of elevated ICP, with a positive likeli-
hood ratio of 6.93 in non-TBI.25 Despite these promising
results, they should be interpreted with caution as their compar-
ison was not exclusive to the gold standard of invasive ICP
monitoring.
Given the methodological limitations of the available
studies, specifically the lack of a large, prospective trial with
a gold standard comparator, there is limited high-quality evi-
dence for the use of POCUS in the diagnosis of elevated ICP.
Kareemi et al
In the hands of an experienced operator, POCUS findings may
add additional information to other clinical signs of elevated
ICP, but cannot be depended upon in isolation.
Invasive Intracranial Monitoring
Invasive intracranial monitoring remains the gold standard for
measuring and diagnosing elevated ICP.26 Invasive monitoring
is typically done by placement of either an intraparenchymal
sensor or external ventricular drain (EVD), with the latter
having the advantage of permitting cerebrospinal fluid drainage
if needed. Despite its widespread use, however, there is conflict-
ing evidence that invasive ICP monitoring improves patient
outcomes.27,28 The landmark BEST:TRIP trial found no
improvement in neurologic outcomes or mortality with a treat-
ment algorithm utilizing invasive ICP monitoring compared to
an algorithm involving serial physical examinations and CT
scans.28 However, this trial did have important limitations
including a lack of external validity (performed in Bolivian
and Ecuadorian intensive care units where the standard of
care may vary significantly from other countries, particularly
in regards to pre- and post-hospital care) and a composite
outcome that weighted mortality similarly to individual compo-
nents of functional and cognitive tests. Although invasive ICP
monitoring may provide valuable information on response to
advanced management such as hyperosmolar therapy, a
normal ICP reading in isolation is insufficient to rule out ele-
vated pressure.26 Various factors, including focal lesions, may
prevent accurate measurement of ICP by monitors, making
serial physical examinations and neuroimaging vital in acute
resuscitation scenarios even if a monitor is in place.
Additionally, the use of invasive ICP monitoring is not
without risks. One review found the infection rate of EVDs to
be as high as 22%.29 EVD-related infections were associated
with prolonged hospital stay, increased cost of care, and
overall mortality.30 In addition to other complications, includ-
ing postprocedural hemorrhage and misplacement, one must
also consider the potential harm from delaying other diagnostic
and therapeutic interventions during monitor insertion.
Guideline recommendations for the routine use of invasive
ICP monitors is specific to underlying etiology; for example,
routine monitoring is not recommended for ischemic stroke15
but is recommended for TBI.9 A consensus statement by the
International Multidisciplinary Consensus Conference on
Multimodality Monitoring in Neurocritical Care recommends
that ICP monitoring be incorporated in protocolized care for
patients with acute brain injury in addition to imaging and clin-
ical evaluation, with the indications and methods for monitoring
tailored to the specific pathology.31
Extrapolating these data to acute scenarios in which the
underlying etiology may be unknown and competing manage-
ment priorities exist, the decision to place an invasive ICP
monitor needs to balance the potential benefits with its inherent
risks. The information provided by the monitor may be partic-
ularly helpful in the hours, rather than minutes, following acute
resuscitation to assess ongoing ICP fluctuations and response to
3
therapy. Compared to an intraparenchymal monitor, the addi-
tional therapeutic benefit of fluid drainage with an EVD must
be weighed by additional risks, particularly with insertion in
the absence of hydrocephalus. Therefore, it may be reasonable
to defer the placement of an invasive ICP monitor, while initial
management steps are initiated, ensuring that serial clinical
examinations and imaging studies are used to monitor ICP in
the interim.
Management
Rapid assessment and management of elevated ICP is para-
mount in the prevention of secondary brain injury. Several
organizations have released detailed recommendations for the
management of specific etiologies of elevated ICP, including
TBI,9,12 intracerebral hemorrhage,14 subarachnoid hemor-
rhage,13 and acute ischemic stroke.15 More recently, the
Neurocritical Care Society published guidelines on the manage-
ment of acute cerebral edema.10 Collectively, they lack a sys-
tematic approach to the acute resuscitation of critically ill
patient with undifferentiated etiology of elevated ICP. Below,
we will review the current body of evidence for various inter-
ventions, with the ultimate goal of reducing or stabilizing eleva-
tions in ICP while more definitive management for the specific
underlying cause is arranged. We present a generally linear
approach to management starting with the simplest methods
and proceeding to more involved or invasive steps with less
clear evidence of benefit. These management steps are summa-
rized in Table 1.
Initial Assessment and Patient Positioning
As with any unstable patient, one should begin by assessing the
ABCs (Airway, Breathing, Circulation). Many patients with ele-
vated ICP will have neurological dysfunction resulting in impaired
ability to protect their airway or compromised ventilation.
Therefore, it is important to anticipate and prepare for endotracheal
intubation early (see section on “Neuroprotective Intubation”
below). The patient must receive appropriate sedation and analge-
sia, as pain or agitation may cause further elevations in ICP.
Possible treatments include rapid-onset, short-acting agents such
as fentanyl and ketamine.
Targeting normal vital signs will mitigate secondary brain
injury. This includes normotension (100-180 mm Hg; acknowl-
edging there is limited evidence for a particular range in the
undifferentiated patient, and that prevention of hypotension
should remain the priority), normoxia (≥94% SpO2) and nor-
mothermia (36°C-37.8°C). Ideal blood pressure treatment uti-
lizes rapid onset, short-acting and titratable medications such
as labetalol for hypertension or norepinephrine for hypotension.
Elevated ICP itself should not cause hypotension, so the pres-
ence of hypotension should prompt a thorough search for
other causes. Regarding targeted temperature management,
multiple guidelines recommend aggressively targeting normo-
thermia using core-temperature monitoring and standard or
advanced temperature-regulating devices.9,13–15 Due to the
4 Journal of Intensive Care Medicine 0(0)

Table 1. Fundamental Management Principles in the Initial Empiric Treatment of Acutely Elevated Intracranial Pressure.

Treatment Goal Step/Target Example Agent

Positioning Promote cerebral venous drainage • Head of bed 30° NA

• Neck midline
• Relieve jugular vein
compression
Vital Signs Maintain cerebral perfusion, mitigate secondary SpO2 ≥ 94% NA
injury SBP 100-180a • Labetalol for hypertension
• Norepinephrine for
hypotension
Ventilation: NA
• PaCO2 35-38 mm Hg
• ETCO2 32-35 mm Hg
If signs of herniation,
hyperventilate:
• PaCO2 32-35 mm Hg
• ETCO2 28-32 mm Hg

Temperature 36°C-37.8 °C NA
• Diligently avoid fever
Airway Support oxygenation and ventilation while See Table 2 for details NA
protecting the airway.
Symptoms Prevent intracranial pressure spikes, decrease Pain • Fentanyl
metabolic demand • Ketamine
Agitation/Anxiety • Propofol
• Dexmedetomidine
Nausea/Vomiting • Ondansetron
Hyperosmolar Reduce cerebral edema via osmotic gradient NA • Hypertonic saline
Therapy • Mannitol

Abbreviations: ETCO2, end-tidal concentration carbon dioxide; PaCO2, arterial partial pressure carbon dioxide; SBP, systolic blood pressure; SpO2, oxygen
saturation.
a
If underlying etiology known, use specific guideline recommendations for perfusion target.

risk of severe adverse physiologic effects, therapeutic hypother-
mia is not recommended in the acute phase of treatment and is
best reserved as a refractory or intraoperative treatment option
for specific etiologies of elevated ICP, which is beyond the
scope of this review.
Simple maneuvers to optimize patient positioning are widely
recommended across guidelines and, given their low risk of
harm, should be employed immediately for all patients with
suspected raised ICP.9,31,32 The head of the bed should be
raised to 30°, and the patient’s head and neck kept midline to
facilitate venous drainage from the cerebral vasculature. If the
patient has an intracranial monitor in place, it is important to
level and zero the device at the new position before proceeding
with other treatments. Noxious stimuli such as tracheal suction-
ing should be minimized to avoid further elevating ICP.
Neuroprotective Intubation
Intubation poses unique risks to the patient with elevated ICP,
as stimulation via laryngoscopy may increase heart rate,
increase blood pressure, and induce bronchospasm, whereas
utilization of induction agents may induce hypotension, poten-
tially compromising the patient’s hemodynamic status.
Therefore, these patients should be considered to have physio-
logically challenging airways. The procedure should be done by
the most experienced provider to reduce the risk of prolonged
attempt and subsequent hypoxia, as well as unnecessary stimu-
lation from multiple attempts. The interventions discussed
below are summarized in Table 2.
While the intubation equipment is being prepared, the non-
invasive ICP management steps described above should be con-
tinued. During preoxygenation, patients should be pretreated
with fentanyl at least 3 minutes before induction, as short-acting
opioids have been shown to mitigate elevations in heart rate and
blood pressure during rapid sequence intubation (RSI33) as well
as elevations in ICP during noxious procedures in brain-injured
patients.34 Hemodynamic changes should be anticipated with
vasopressor therapy, which should be prepared and ready for
immediate infusion.
The use of intravenous (IV) lidocaine for pretreatment in
neuroprotective intubation was historically based upon a
small trial of 20 patients who underwent elective neurosurgery
for cerebral malignancy.35 Since then, 2 systematic reviews of
TBI patients undergoing RSI found no benefit of IV lidocaine
for decreasing elevated ICP.36,37 A separate systematic review
similarly found poor evidence that IV lidocaine is effective at
Kareemi et al 5

Table 2. Approach to Neuroprotective Intubation of Patients With topical lidocaine may be helpful in situations where it does not
Acutely Elevated Intracranial Pressure. delay intubation or jeopardize maintenance of normal ICP.
Step Details and Example Agents
Induction should be done with a hemodynamically stable
agent that does not induce hypotension or negative chronotropy,
Preparation Assess airway for difficult anatomic/physiologic such as ketamine or etomidate.44,45 Historically, ketamine was
predictors avoided as a neuroprotective induction agent due to concerns
Preoxygenation • Nasal prongs about its potential to raise ICP.46 More recently, large systematic
• Nonrebreather
reviews found little evidence supporting this effect on ICP44 nor
• Apneic oxygenation
Positioning • Head of bed 30° reduction of cerebral perfusion pressures in critically ill patients.47
• Neck midline Similarly, a retrospective study of trauma patients undergoing RSI
• Sniffing position found no difference in mortality or patient outcomes between the
Pretreatment Give >3 min preinduction use of ketamine versus etomidate for induction in the subset of
• Vasopressor patients with TBI.45 Because of its vasodilating properties, propo-
- Norepinephrine fol is best reserved for hypertensive patients but can also be used
- Phenylephrine
for normotensive patients provided hypotension is anticipated and
• Analgesic
- Fentanyl treated with vasopressor therapy.
• Anaesthetic (if time permits) The paralytic of choice for neuroprotective RSI is succinyl-
- Topical lidocaine choline or rocuronium, depending on institutional availability
or provider preference. Concerns have been raised that succi-
Induction • Ketamine nylcholine may elevate ICP based on studies of elective
• Etomidate neurosurgical patients48,49; however, subsequent studies have
• Propofol (if significantly hypertensive)
not demonstrated this nor have they shown an attenuation of
Paralytic • Rocuronium
• Succinylcholine elevation of ICP using pretreatment with a nondepolarizing
Postintubation • Analgesic neuromuscular blocking agent.50 Succinylcholine is a safe
- Fentanyl option and has the potential benefit of decreasing time until
- Hydromorphone repeat neurologic assessment due to its decreased duration of
• Sedative effect compared with rocuronium. Usual contraindications for
- Dexmedetomidine succinylcholine, such as for patients with acute hyperkalemia,
- Propofol
should be respected.
During endotracheal tube placement, particular care should be
made for a gentle, nontraumatic insertion that minimizes glottic
stimulation. Continuous analgesia and sedation following intuba-
tion should be maintained using opioids and either dexmedetomi-
attenuating ICP spikes nor improving patient outcomes.38 dine or propofol, titrated to clinical effect (as measured by a
Furthermore, a Cochrane review found that pretreatment standardized sedation scale) and resolution of signs of elevated
using IV lidocaine in elective operations resulted in elevated ICP. The 2019 Seattle International Severe Traumatic Brain
odds ratios for bradycardia, hypotension, and other adverse Injury Consensus Conference (SIBICC) guidelines recommend
events.39 Other small studies have found similar results suggest- considering a single dose of a neuromuscular paralytic agent in
ing that IV lidocaine at doses of 2 mg/kg pretreatment40 may an adequately sedated patient to assess for efficacy in decreasing
induce hypotension and a drop in cerebral perfusion pressure.38 ICP and proceeding with an infusion if efficacious.12
Taken together, the evidence suggests that at best, IV lidocaine
provides minimal benefit, and at worst, results in significant
physiologic derangements. Hyperosmolar Therapy
Evidence supporting the use of topical lidocaine for pretreat- Hyperosmolar therapy may reduce ICP via 2 primary physio-
ment is also limited. A small trial of 21 patients found that instill- logic mechanisms. Initially, a rheologic effect occurs via the
ing topical lidocaine through an endotracheal tube prior to expansion of plasma volume and reduction of blood viscosity,
suctioning was safe and effective at reducing stimulation-induced thereby improving cerebral oxygen delivery and resulting in
spikes in ICP.41 Although this could indicate a blunting of sym- cerebral vasoconstriction.51 Secondly, the production of an
pathetic response induced by topical lidocaine, suctioning is osmolar gradient in the blood draws water from the extravascu-
notably different from endotracheal intubation and thus these lar (ie, brain tissue) into the intravascular compartment, thereby
results should be interpreted with caution. Topical lidocaine is promoting venous drainage and reducing ICP.51 Hypertonic
used occasionally in neuroanesthesia for similar reasons; saline (HTS) and mannitol have been widely used for the treat-
however, the evidence supporting it is largely confined to case ment of TBI for decades.52 The 2020 guidelines from the
reports and anecdotal experience.42 Additionally, topical lido- Neurocritical Care Society support the use of hyperosmolar
caine takes 4 to 5 min to reach maximal effect, which may therapy in the management of elevated ICP from TBI, subarach-
make it impractical in acute situations.43 Based on this evidence, noid hemorrhage, intracerebral hemorrhage, and acute ischemic
6 Journal of Intensive Care Medicine 0(0)
stroke based on demonstrated efficacy in several randomized
controlled trials.10
The effect of mannitol on ICP is thought to begin in minutes,
peaking between 15 and 120 minutes and lasting a total of 1 to 5
hours based on sparse pharmacodynamic data.53,54 Notably, it
has been shown to cause adverse effects including hypovolemia
and renal failure.55,56 Although mannitol was formerly recom-
mended as the first-line agent for hyperosmolar ICP therapy,57 a
meta-analysis found HTS to be more effective than mannitol at
reducing ICP without the associated adverse effects.58 A small
RCT found that HTS had a faster time to onset and a more
robust ICP reduction when mannitol failed to reduce ICP in TBI
patients.59
The NCS guidelines generally recommend the use of HTS over
mannitol for the treatment of elevated ICP in TBI, subarachnoid
hemorrhage, and intracerebral hemorrhage,10 while acknowledg-
ing the absence of large, high-quality trials on the subject. The
2019 SIBICC guidelines recommend targeting serum sodium of
less than 155 mEq/L and osmolality less than 320 mEq/L, with
regular monitoring every 4 to 6 hours.12 As an alternative to
serum osmoles, ensuring a normal osmolar gap is a useful moni-
toring target when initiating mannitol therapy.60 When initiating
hyperosmolar therapy, a Foley catheter should be placed to
monitor urine output.
Hyperventilation
Hyperventilation therapy relies on the principle that inducing
cerebral arterial vasoconstriction via hypocapnia results in
reduced cerebral blood volume and therefore decreases ICP.
Although hyperventilation has been shown to rapidly reduce
ICP, it has not been associated with improved patient outcomes
in TBI.61,62 Nonetheless, it is strongly recommended by the
NCS guidelines, with the rationale that the benefit of reducing
harm from elevated ICP outweighs the risk of cerebral ische-
mia, which has only been demonstrated with prolonged
employment.10 In scenarios where hyperventilation is used, it
is best employed as a temporizing measure for impending or
active cerebral herniation until more definitive treatment (eg,
neurosurgery) can be provided.
Initially, a low-normal PaCO2 between 35 and 38 mm Hg
and end-tidal CO2 between 32 and 35 mm Hg (to account for
dead space ventilation in mechanically ventilated patients
with an endotracheal tube) should be targeted. If elevated ICP
persists, the target may be lowered to 32 to 35 mm Hg
PaCO2 and 28 to 32 mm Hg end-tidal CO2 for a maximum of
2 hours to mitigate ischemic brain injury.
Corticosteroids
There is little evidence to support the use of corticosteroids for
several etiologies of elevated ICP. The landmark CRASH-1 trial
found a higher risk of mortality within 2 weeks with IV corticoste-
roid use in 10 008 adult TBI patients.63 Corticosteroid use has
shown minimal benefit with increased rates of complications in
intracerebral hemorrhage10,64 and ischemic stroke.65
In the case of bacterial meningitis, the use of corticosteroids
has not shown consistent improvement in patient mortality in
several meta-analyses,66,67 although it does appear to reduce
rates of sensorineural hearing loss.68 In 2004, the Infectious
Diseases Society of America released guidelines supporting
the use of corticosteroids in adults with bacterial meningitis.69
Although limited evidence exists on the use of steroids for ele-
vated ICP caused by central nervous system tumors, there is
some evidence it may be effective specifically for temporary
symptomatic relief of the vasogenic edema caused by brain
metastases.70
Corticosteroids should, therefore, be reserved for patients
with elevated ICP only in the context of bacterial meningitis
or central nervous system tumors and not empirically in the
patient with an undifferentiated underlying cause.
Conclusion
Acutely elevated ICP is a life-threatening condition that may
result from a variety of neurologic disease processes. Early rec-
ognition depends on the findings of physical examination and
neuroimaging modalities, with the addition of an invasive
monitor if time and resources allow. Early treatment may
need to be initiated before the underlying etiology is known,
in which case specific treatment guidelines are less helpful.
An empiric approach based on hemodynamic control and pre-
vention of secondary brain injury can optimize the initial resus-
citation while further investigations and definitive management
are arranged. In cases where the patient’s ability to protect their
airway or respiratory status is compromised, neuroprotective
intubation should be performed by the most experienced pro-
vider. Adequate analgesia and sedation can prevent abrupt
increases in ICP, while hyperosmolar therapy and hyperventila-
tion can be used for patients that continue to display signs of
elevated ICP despite initial management. As future studies
and trials elucidate the value of specific medications and inter-
ventions, clinicians must continue to rely on a multimodal
approach to these complex, critical situations.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
ORCID iDs
Hashim Kareemi https://orcid.org/0000-0001-8599-1576
Ariel Hendin https://orcid.org/0000-0002-4886-1710
References
1. Lannoo E, Van Rietvelde F, Colardyn F, et al. Early predictors of
mortality and morbidity after severe closed head injury. J
Neurotrauma. 2000;17(5):403-414.
Kareemi et al
2. Narayan RK, Greenberg RP, Miller JD, et al. Improved confidence
of outcome prediction in severe head injury. A comparative anal-
ysis of the clinical examination, multimodality evoked potentials,
CT scanning, and intracranial pressure. J Neurosurg.
1981;54(6):751-762.
3. Czosnyka M, Guazzo E, Whitehouse M, et al. Significance of
intracranial pressure waveform analysis after head injury. Acta
Neurochir (Wien). 1996;138(5):531-541.
4. Sorrentino E, Diedler J, Kasprowicz M, et al. Critical thresholds
for cerebrovascular reactivity after traumatic brain injury.
Neurocrit Care. 2012;16(2):258-266.
5. Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral
haemorrhage: current approaches to acute management. Lancet.
2018;392(10154):1257-1268.
6. Jauch EC, Saver JL, Adams HP, Jr., et al. Guidelines for the early
management of patients with acute ischemic stroke: a guideline for
healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2013;44(3):870-947.
7. Rangel-Castilla L, Gopinath S, Robertson CS. Management of
intracranial hypertension. Neurol Clin. 2008;26(2):521-541.
8. Cushing H. Studies in Intracranial Physiology & Surgery. Oxford
University Press; 1926.
9. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the man-
agement of severe traumatic brain injury, fourth edition.
Neurosurgery. 2017;80(1):6-15.
10. Cook AM, Morgan Jones G, Hawryluk GWJ, et al. Guidelines for
the acute treatment of cerebral edema in neurocritical care patients.
Neurocrit Care. 2020;32(3):647-666.
11. Cadena R, Shoykhet M, Ratcliff JJ. Emergency neurological life
support: intracranial hypertension and herniation. Neurocrit
Care. 2017;27(Suppl 1):82-88.
12. Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm
for patients with intracranial pressure monitoring: the Seattle
International Severe Traumatic Brain Injury Consensus Conference
(SIBICC). Intensive Care Med. 2019;45(12):1783-1794.
13. Connolly ES, Rabinstein AA, Carhuapoma JR, et al. Guidelines for
the management of aneurysmal subarachnoid hemorrhage: a guideline
for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2012;43(6):1711-1737.
14. Hemphill JC, Greenberg SM, Anderson CS, et al. Guidelines for the
management of spontaneous intracerebral hemorrhage: a guideline
for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2015;46(7):2032-2060.
15. Wijdicks EF, Sheth KN, Carter BS, et al. Recommendations for
the management of cerebral and cerebellar infarction with swell-
ing: a statement for healthcare professionals from the American
Heart Association/American Stroke Association. Stroke.
2014;45(4):1222-1238.
16. Rosenberg JB, Shiloh AL, Savel RH, Eisen LA. Non-invasive
methods of estimating intracranial pressure. Neurocrit Care.
2011;15(3):599-608.
17. Fernando SM, Tran A, Cheng W, et al. Diagnosis of elevated
intracranial pressure in critically ill adults: systematic review
and meta-analysis. Br Med J. 2019;366:l4225.
18. Ter Avest E, Taylor S, Wilson M, Lyon RL. Prehospital clini-
cal signs are a poor predictor of raised intracranial pressure fol-
lowing traumatic brain injury. Emerg Med J. 2021;38(1):21-
26.
19. Kalmar AF, Van Aken J, Caemaert J, Mortier EP, Struys MM.
Value of cushing reflex as warning sign for brain ischaemia
during neuroendoscopy. Br J Anaesth. 2005;94(6):791-799.
7
20. Greer DM, Shemie SD, Lewis A, et al. Determination of brain
death/death by neurologic criteria: the world brain death project.
JAMA. 2020;324(11):1078-1097.
21. Kristiansson H, Nissborg E, Bartek JJr., Andresen M, Reinstrup P,
Romner B Measuring elevated intracranial pressure through non-
invasive methods: a review of the literature. J Neurosurg
Anesthesiol. 2013;25(4):372-385.
22. Marshall LF, Marshall SB, Klauber MR, et al. The diagnosis of
head injury requires a classification based on computed axial
tomography. J Neurotrauma. 1992;9(Suppl 1):S287-S292.
23. Cardim D, Schmidt B, Robba C, et al. Transcranial Doppler mon-
itoring of intracranial pressure plateau waves. Neurocrit Care.
2017;26(3):330-338.
24. Behrens A, Lenfeldt N, Ambarki K, Malm J, Eklund A, Koskinen
LO. Transcranial Doppler pulsatility index: not an accurate
method to assess intracranial pressure. Neurosurgery.
2010;66(6):1050-1057.
25. Koziarz A, Sne N, Kegel F, et al. Bedside optic nerve ultrasonog-
raphy for diagnosing increased intracranial pressure: a systematic
review and meta-analysis. Ann Intern Med. 2019;171(12):896-
905.
26. Liotta EM. Management of cerebral edema, brain compression, and
intracranial pressure. Continuum (Minneap Minn). 2021;27(5):
1172-1200.
27. Narayan RK, Kishore PR, Becker DP, et al. Intracranial pressure:
to monitor or not to monitor? A review of our experience with
severe head injury. J Neurosurg. 1982;56(5):650-659.
28. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-
pressure monitoring in traumatic brain injury. N Engl J Med.
2012;367(26):2471-2481.
29. Tavakoli S, Peitz G, Ares W, Hafeez S, Grandhi R. Complications
of invasive intracranial pressure monitoring devices in neurocriti-
cal care. Neurosurg Focus. 2017;43(5):E6.
30. Murthy SB, Moradiya Y, Shah J, Hanley DF, Ziai WC. Incidence,
predictors, and outcomes of ventriculostomy-associated infections
in spontaneous intracerebral hemorrhage. Neurocrit Care.
2016;24(3):389-396.
31. Le Roux P, Menon DK, Citerio G, et al. Consensus summary
statement of the international multidisciplinary consensus confer-
ence on multimodality monitoring in neurocritical care: a state-
ment for healthcare professionals from the Neurocritical Care
Society and the European Society of Intensive Care Medicine.
Intensive Care Med. 2014;40(9):1189-1209.
32. Esquenazi Y, Lo VP, Lee K. Critical care management of cere-
bral edema in brain tumors. J Intensive Care Med.
2017;32(1):15-24.
33. Kim J-T, Shim J-K, Kim SH, et al. Remifentanil vs. lignocaine for
attenuating the haemodynamic response during rapid sequence
induction using propofol: double-blind randomised clinical trial.
Anaesth Intensive Care. 2007;35(1):20-23.
34. Kerr ME, Sereika SM, Orndoff P, et al. Effect of neuromuscular
blockers and opiates on the cerebrovascular response to endotra-
cheal suctioning in adults with severe head injuries. Am J Crit
Care. 1998;7(3):205-217.
35. Bedford RF, Winn HR, Tyson G, Park TS, Jane JA. Lidocaine
Prevents Increased ICP after Endotracheal Intubation. 1980;
Heidelberg.
36. Robinson N, Clancy M. In patients with head injury undergoing
rapid sequence intubation, does pretreatment with intravenous
lignocaine/lidocaine lead to an improved neurological outcome?
A review of the literature. Emerg Med J. 2001;18(6):453-457.
8 Journal of Intensive Care Medicine 0(0)
37. Qi DY, Wang K, Zhang H, et al. Efficacy of intravenous lidocaine
versus placebo on attenuating cardiovascular response to laryngos-
copy and tracheal intubation: a systematic review of randomized
controlled trials. Minerva Anestesiol. 2013;79(12):1423-1435.
38. Samaha T, Ravussin P, Claquin C, Ecoffey C. [Prevention of
increase of blood pressure and intracranial pressure during endo-
tracheal intubation in neurosurgery: esmolol versus lidocaine].
Ann Fr Anesth Reanim. 1996;15(1):36-40.
39. Khan FA, Ullah H. Pharmacological agents for preventing mor-
bidity associated with the haemodynamic response to tracheal
intubation. Cochrane Database Syst Rev. 2013(7):CD004087.
40. Grover VK, Reddy GM, Kak VK, Singh S. Intracranial pressure
changes with different doses of lignocaine under general anaesthe-
sia. Neurol India. 1999;47(2):118-121.
41. Bilotta F, Branca G, Lam A, Cuzzone V, Doronzio A, Rosa G.
Endotracheal lidocaine in preventing endotracheal suctioning-induced
changes in cerebral hemodynamics in patients with severe head trauma.
Neurocrit Care. 2008;8(2):241-246.
42. Hajat Z, Unger Z. Near misses in neuroanesthesia. In: Prabhakar H,
Ali Z, eds. Textbook of Neuroanesthesia and Neurocritical Care:
Volume I—Neuroanesthesia. Springer Singapore; 2019:403-411.
43. Schønemann NK, van der Burght M, Arendt-Nielsen L, Bjerring
P. Onset and duration of hypoalgesia of lidocaine spray applied
to oral mucosa–a dose response study. Acta Anaesthesiol Scand.
1992;36(7):733-735.
44. Gregers MCT, Mikkelsen S, Lindvig KP, Brøchner AC. Ketamine
as an anesthetic for patients with acute brain injury: a systematic
review. Neurocrit Care. 2020;33(1):273-282.
45. Upchurch CP, Grijalva CG, Russ S, et al. Comparison of etomi-
date and ketamine for induction during rapid sequence intubation
of adult trauma patients. Ann Emerg Med. 2017;69(1):24-33.e22.
46. Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral
circulation and metabolism in man. Anesthesiology.
1972;36(1):69-75.
47. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose
NG, Hohl CM. The effect of ketamine on intracranial and cerebral
perfusion pressure and health outcomes: a systematic review. Ann
Emerg Med. 2015;65(1):43-51.e42.
48. Marsh M, Dunlop B, Shapiro H, Gagnon R, Rockoff M.
Succinylcholine-intracranial pressure effects in neurosurgical
patients. Paper presented at: Anesthesia and Analgesia, 1980.
49. Minton MD, Grosslight K, Stirt JA, Bedford RF. Increases in
intracranial pressure from succinylcholine: prevention by
prior nondepolarizing blockade. Anesthesiology. 1986;65(2):
165-169.
50. Clancy M, Halford S, Walls R, Murphy M. In patients with head
injuries who undergo rapid sequence intubation using succinyl-
choline, does pretreatment with a competitive neuromuscular
blocking agent improve outcome? A literature review. Emerg
Med J. 2001;18(5):373-375.
51. Hinson HE, Stein D, Sheth KN. Hypertonic saline and mannitol therapy
in critical care neurology. J Intensive Care Med. 2013;28(1):3-11.
52. Burgess S, Abu-Laban RB, Slavik RS, Vu EN, Zed PJ. A system-
atic review of randomized controlled trials comparing hypertonic
sodium solutions and mannitol for traumatic brain injury: implica-
tions for emergency department management. Ann Pharmacother.
2016;50(4):291-300.
53. Marshall LF, Smith RW, Rauscher LA, Shapiro HM. Mannitol
dose requirements in brain-injured patients. J Neurosurg.
1978;48(2):169-172.
54. Sorani MD, Morabito D, Rosenthal G, Giacomini KM, Manley
GT. Characterizing the dose-response relationship between man-
nitol and intracranial pressure in traumatic brain injury patients
using a high-frequency physiological data collection system. J
Neurotrauma. 2008;25(4):291-298.
55. Diringer MN, Zazulia AR. Osmotic therapy: fact and fiction.
Neurocrit Care. 2004;1(2):219-234.
56. Oken DE. Renal and extrarenal considerations in high-dose man-
nitol therapy. Renal Fail. 1994;16(1):147-159.
57. Surgeon AAoNSBTFCoN. Guidelines for the management of
severe traumatic brain injury. J Neurotrauma. 2007;24(Suppl 1):
S1-106.
58. Kamel H, Navi BB, Nakagawa K, Hemphill JC, Ko NU.
Hypertonic saline versus mannitol for the treatment of elevated
intracranial pressure: a meta-analysis of randomized clinical
trials. Crit Care Med. 2011;39(3):554-559.
59. Harutjunyan L, Holz C, Rieger A, Menzel M, Grond S, Soukup
J. Efficiency of 7.2% hypertonic saline hydroxyethyl starch
200/0.5 versus mannitol 15% in the treatment of increased
intracranial pressure in neurosurgical patients—a randomized
clinical trial [ISRCTN62699180]. Crit Care. 2005;9(5):
R530-R540.
60. García-Morales EJ, Cariappa R, Parvin CA, Scott MG, Diringer
MN. Osmole gap in neurologic-neurosurgical intensive care
unit: its normal value, calculation, and relationship with mannitol
serum concentrations. Crit Care Med. 2004;32(4):986-991.
61. Stocchetti N, Maas AI, Chieregato A, van der Plas AA.
Hyperventilation in head injury: a review. Chest. 2005;127(5):
1812-1827.
62. Curley G, Kavanagh BP, Laffey JG. Hypocapnia and the injured
brain: more harm than benefit. Crit Care Med. 2010;38(5):1348-
1359.
63. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous
corticosteroids on death within 14 days in 10008 adults with
clinically significant head injury (MRC CRASH trial): rando-
mised placebo-controlled trial. Lancet. 2004;364(9442):1321-
1328.
64. Feigin VL, Anderson N, Rinkel GJ, Algra A, van Gijn J, Bennett
DA. Corticosteroids for aneurysmal subarachnoid haemorrhage
and primary intracerebral haemorrhage. Cochrane Database Syst
Rev. 2005(3):CD004583.
65. Sandercock PA, Soane T. Corticosteroids for acute ischaemic
stroke. Cochrane Database Syst Rev. 2011;2011(9):CD000064.
66. van de Beek D, de Gans J, Tunkel AR, Wijdicks EF.
Community-acquired bacterial meningitis in adults. N Engl J
Med. 2006;354(1):44-53.
67. Vardakas KZ, Matthaiou DK, Falagas ME. Adjunctive dexame-
thasone therapy for bacterial meningitis in adults: a meta-analysis
of randomized controlled trials. Eur J Neurol. 2009;16(6):662-
673.
68. Brouwer MC, McIntyre P, de Gans J, Prasad K, van de Beek D
Corticosteroids for acute bacterial meningitis. Cochrane
Database Syst Rev. 2010(9):CD004405.
69. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for
the management of bacterial meningitis. Clin Infect Dis.
2004;39(9):1267-1284.
70. Ryken TC, McDermott M, Robinson PD, et al. The role of steroids
in the management of brain metastases: a systematic review and
evidence-based clinical practice guideline. J Neurooncol.
2010;96(1):103-114.