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Evaluation and management of elevated

intracranial pressure in adults

Contributors Disclosures

Date

INTRODUCTION — Elevated intracranial pressure (ICP) is a potentially

devastating complication of neurologic injury. Elevated ICP may
complicate trauma, central nervous system (CNS) tumors,
hydrocephalus, hepatic encephalopathy, and impaired CNS venous
outflow (table 1) [1]. Successful management of patients with elevated
ICP requires prompt recognition, the judicious use of invasive
monitoring, and therapy directed at both reducing ICP and reversing its
underlying cause.

The evaluation and management of adult patients with elevated ICP will
be reviewed here. Elevated intracranial pressure in children and specific
causes and complications of elevated ICP (eg, ischemic stroke,
intracerebral hemorrhage, traumatic brain injury) are discussed
separately. (See "Elevated intracranial pressure (ICP) in children" and
"Management of acute severe traumatic brain injury", section on
'Intracranial pressure' and "Initial assessment and management of acute
stroke" and "Spontaneous intracerebral hemorrhage: Treatment and
prognosis" and "Treatment of aneurysmal subarachnoid hemorrhage",
section on 'Management of complications'.)

PHYSIOLOGY — Intracranial pressure is normally ≤15 mmHg in adults,

and pathologic intracranial hypertension (ICH) is present at pressures
≥20 mmHg. ICP is normally lower in children than adults, and may be
subatmospheric in newborns [2]. Homeostatic mechanisms stabilize ICP,
with occasional transient elevations associated with physiologic events,
including sneezing, coughing, or Valsalva maneuvers.
Intracranial components — In adults, the intracranial compartment is
protected by the skull, a rigid structure with a fixed internal volume of
1400 to 1700 mL. Under physiologic conditions, the intracranial
contents include (by volume) [3]:

Brain parenchyma — 80 percent

Cerebrospinal fluid — 10 percent
Blood — 10 percent

Pathologic structures, including mass lesions, abscesses, and

hematomas also may be present within the intracranial compartment.
Since the overall volume of the cranial vault cannot change, an increase
in the volume of one component, or the presence of pathologic
components, necessitates the displacement of other structures, an
increase in ICP, or both. Thus, ICP is a function of the volume and
compliance of each component of the intracranial compartment, an
interrelationship known as the Monro-Kellie doctrine [4,5].

The volume of brain parenchyma is relatively constant in adults, although

it can be altered by mass lesions or in the setting of cerebral edema
(figure 1). The volumes of CSF and blood in the intracranial space vary to
a greater degree. Abnormal increases in the volume of any component
may lead to elevations in ICP.

CSF is produced by the choroid plexus and elsewhere in the central

nervous system (CNS) at a rate of approximately 20 mL/h (500 mL/day)
[6]. CSF is normally resorbed via the arachnoid granulations into the
venous system. Problems with CSF regulation generally result from
impaired outflow caused by ventricular obstruction or venous
congestion; the latter can occur in patients with sagittal (or other)
venous sinus thrombosis. Much less frequently, CSF production can
become pathologically increased; this may be seen in the setting of
choroid plexus papilloma. (See "Cerebrospinal fluid: Physiology and
utility of an examination in disease states".)

Cerebral blood flow (CBF) determines the volume of blood in the

intracranial space. CBF increases with hypercapnia and hypoxia. Other
determinants of CBF are discussed below. Autoregulation of CBF may be
impaired in the setting of neurologic injury, and may result in rapid and
severe brain swelling, especially in children [7-9].

In summary, the major causes of increased intracranial pressure include:

Intracranial mass lesions (eg, tumor, hematoma)

Cerebral edema (such as in acute hypoxic ischemic
encephalopathy, large cerebral infarction, severe traumatic brain
injury)
 Increased cerebrospinal fluid (CSF) production, eg, choroid plexus
papilloma
Decreased CSF absorption, eg, arachnoid granulation adhesions
after bacterial meningitis
Obstructive hydrocephalus
Obstruction of venous outflow, eg, venous sinus thrombosis, jugular
vein compression, neck surgery
Idiopathic intracranial hypertension (pseudotumor cerebri)

Intracranial compliance — The interrelationship between changes in the

volume of intracranial contents and changes in ICP defines the
compliance characteristics of the intracranial compartment. Intracranial
compliance can be modeled mathematically (as in other physiologic and
mechanical systems) as the change in volume over the change in
pressure (dV/dP).

The compliance relationship is nonlinear, and compliance decreases as

the combined volume of the intracranial contents increases. Initially,
compensatory mechanisms allow volume to increase with minimal
elevation in ICP. These mechanisms include:

Displacement of CSF into the thecal sac

Decrease in the volume of the cerebral venous blood via
venoconstriction and extracranial drainage

However, when these compensatory mechanisms have been exhausted,

significant increases in pressure develop with small increases in volume,
leading to abnormally elevated ICP (figure 2).

Thus, the magnitude of the change in volume of an individual structure

determines its effect on ICP. In addition, the rate of change in the volume
of the intracranial contents influences ICP. Changes that occur slowly
produce less of an effect than those that are rapid. This can be
recognized clinically in some patients who present with large
meningiomas and minimally elevated or normal ICP. Conversely, other
patients may experience symptomatic elevations in ICP from small
hematomas that develop acutely.

Cerebral blood flow — Following a significant increase in ICP, brain injury

can result from brainstem compression and/or a reduction in cerebral
blood flow (CBF). CBF is a function of the pressure drop across the
cerebral circulation divided by the cerebrovascular resistance, as
predicted by Ohm's law [10]:

CBF = (CAP - JVP) ÷ CVR

where CAP is carotid arterial pressure, JVP is jugular venous pressure,

and CVR is cerebrovascular resistance.

Cerebral perfusion pressure (CPP) is a clinical surrogate for the

adequacy of cerebral perfusion. CPP is defined as mean arterial pressure
(MAP) minus ICP.

CPP = MAP - ICP

Autoregulation — CBF is normally maintained at a relatively constant

level by cerebrovascular autoregulation of CVR over a wide range of CPP
(50 to 100 mmHg) (figure 3) [11,12]. However, autoregulation of CVR
can become dysfunctional in certain pathologic states, most notably
stroke or trauma. In this setting, the brain becomes exquisitely sensitive
to even minor changes in CPP [11-13].

Another important consideration is that the set-point of autoregulation is

also changed in patients with chronic hypertension. With mild to
moderate elevations in blood pressure, the initial response is arterial and
arteriolar vasoconstriction. This autoregulatory process both maintains
tissue perfusion at a relatively constant level and prevents the increase in
pressure from being transmitted to the smaller, more distal vessels [11].
As a result, acute reductions in blood pressure, even if the final value
remains within the normal range, can produce ischemic symptoms in
patients with chronic hypertension (figure 3) [11].

Cerebral perfusion pressure — Conditions associated with elevated ICP,

including mass lesions and hydrocephalus, can be associated with a
reduction in CPP. This can result in devastating focal or global ischemia.
On the other hand, excessive elevation of CPP can lead to hypertensive
encephalopathy and cerebral edema due to the eventual breakdown of
autoregulation, particularly if the CPP is >120 mmHg [11,14,15]. A
higher level of CPP is tolerated in patients with chronic hypertension
because the autoregulatory curve has shifted to the right (figure 3)
[11,15]. (See "Moderate to severe hypertensive retinopathy and
hypertensive encephalopathy in adults", section on 'Mechanisms of
vascular injury'.)

Ultimately, global or local reductions in CBF are responsible for the

clinical manifestations of elevated ICP. These manifestations can be
further divided into generalized responses to elevated ICP and herniation
syndromes.

CLINICAL MANIFESTATIONS — Global symptoms of elevated ICP include

headache, which is probably mediated via the pain fibers of cranial nerve
(CN) V in the dura and blood vessels, depressed global consciousness
due to either the local effect of mass lesions or pressure on the midbrain
reticular formation, and vomiting.
Signs include CN VI palsies, papilledema secondary to impaired axonal
transport and congestion (picture 1), spontaneous periorbital bruising
[16] and a triad of bradycardia, respiratory depression, and hypertension
(Cushing's triad, sometimes called Cushing's reflex or Cushing's
response) [3]. While the mechanism of Cushing's triad remains
controversial, many believe that it relates to brainstem compression. The
presence of this response is an ominous finding that requires urgent
intervention.

Focal symptoms of elevated ICP may be caused by local effects in

patients with mass lesions or by herniation syndromes. Herniation results
when pressure gradients develop between two regions of the cranial
vault. The most common anatomical locations affected by herniation
syndromes include subfalcine, central transtentorial, uncal transtentorial,
upward cerebellar, cerebellar tonsillar/foramen magnum, and
transcalvarial (figure 4) [3,17]. (See "Stupor and coma in adults",
section on 'Neurologic examination' and "Stupor and coma in adults",
section on 'Coma syndromes'.)

One notable false localizing syndrome seen following neurologic injury,

referred to as Kernohan's notch phenomenon, consists of the
combination of contralateral pupillary dilatation and ipsilateral weakness
[18,19]. Because the diagnostic accuracy of signs and symptoms is
limited, the findings described above may be inconstant or unreliable in
any given case. Use of radiologic studies may support the diagnosis;
however, the most reliable method of diagnosing elevated ICP is to
measure it directly.

ICP MONITORING — Empiric therapy for presumed elevated ICP is

unsatisfactory because CPP cannot be monitored reliably without
measurement of ICP. Furthermore, most therapies directed at lowering
ICP are effective for limited and variable periods of time. In addition,
these treatments may have serious side effects. Therefore, while initial
steps to control ICP may, by necessity, be performed without the benefit
of ICP monitoring, an important early goal in management of the patient
with presumed elevated ICP is placement of an ICP monitoring device.

The purpose of monitoring ICP is to improve the clinician's ability to

maintain adequate CPP and oxygenation. The only way to reliably
determine CPP (defined as the difference between MAP and ICP) is to
continuously monitor both ICP and blood pressure (BP). In general,
these patients are managed in intensive care units (ICUs) with an ICP
monitor and arterial line. The combination of ICP monitoring and
concomitant management of CPP may improve patient outcomes,
particularly in patients with closed head trauma [20-23]. The specific
therapeutic targets for CPP in patients with traumatic brain injury are
discussed separately. (See "Management of acute severe traumatic brain
injury", section on 'Cerebral perfusion pressure'.)

Indications — The diagnosis of elevated ICP generally is based on

clinical findings, and corroborated by imaging studies and the patient's
medical history. Closed head injury is one of the most frequent and
best-studied indications for ICP monitoring. Much of the current practice
of ICP monitoring has been derived from clinical experience with closed
head trauma patients [24]. Indications for ICP monitoring in this
indication is discussed in detail separately. (See "Management of acute
severe traumatic brain injury", section on 'Intracranial pressure'.)

Role of computed tomography — Although CT scans may suggest

elevated ICP based on the presence of mass lesions, midline shift, or
effacement of the basilar cisterns (image 1), patients without these
findings on initial CT may have elevated ICP. This was demonstrated in a
prospective study of 753 patients treated at four major head injury
research centers in the United States, which found patients whose initial
CT scan did not show a mass lesion, midline shift, or abnormal cisterns
had a 10 to 15 percent chance of developing elevated ICP during their
hospitalization [25].

Other studies have shown that up to one-third of patients with initially

normal scans developed CT scan abnormalities within the first few days
after closed head injury [26,27]. Together, these findings demonstrate
that ICP can be elevated even in the setting of a normal initial CT,
demonstrating the importance of invasive monitoring in high-risk
patients and the role of follow-up imaging in patients who develop
clinical evidence of increased ICP during hospitalization.

Since ICP monitoring is associated with a small risk of serious

complications, including CNS infection and intracranial hemorrhage, it is
reasonable to try to limit its use to patients most at risk of elevated ICP
[28]. In general, invasive monitoring of ICP is indicated in patients who
are [29]:

Suspected to be at risk for elevated ICP

Comatose (Glasgow Coma Scale <8) (table 2)
Diagnosed with a process that merits aggressive medical care

Types of monitors — There are four main anatomical sites used in the
clinical measurement of ICP: intraventricular, intraparenchymal,
subarachnoid, and epidural (figure 5) [30]. Noninvasive and metabolic
monitoring of ICP has also been studied, but the clinical value of these
methods is unclear at present. Each technique requires a unique
monitoring system, and has associated advantages and disadvantages.
Intraventricular — Intraventricular monitors are considered the "gold
standard" of ICP monitoring catheters. They are surgically placed into
the ventricular system and affixed to a drainage bag and pressure
transducer with a three-way stopcock. Intraventricular monitoring has
the advantage of accuracy, simplicity of measurement, and the unique
characteristic of allowing for treatment of some causes of elevated ICP
via drainage of CSF.

The primary disadvantage is infection, which may occur in up to 20

percent of patients. This risk increases the longer a device is in place
[31,32]. Prophylactic catheter changes did not appear to reduce the risk
of infection [32]. (See "Infections of central nervous system shunts and
other devices".)

A further disadvantage of intraventricular systems includes a small

(approximately 2 percent) risk of hemorrhage during placement; this risk
is greater in coagulopathic patients. In addition, it may be technically
difficult to place an intraventricular drain into a small ventricle,
particularly in the setting of trauma and cerebral edema complicated by
ventricular compression [33].

Intraparenchymal — Intraparenchymal devices consist of a thin cable

with an electronic or fiberoptic transducer at the tip. The most widely
used device is the fiberoptic Camino system. These monitors can be
inserted directly into the brain parenchyma via a small hole drilled in the
skull. Advantages include ease of placement, and a lower risk of infection
and hemorrhage (<1 percent) than with intraventricular devices [34-36].

Disadvantages include the inability to drain CSF for diagnostic or

therapeutic purposes and the potential to lose accuracy (or "drift") over
several days, since the transducer cannot be recalibrated following initial
placement [30]. In addition, there is a greater risk of mechanical failure
due to the complex design of these monitors. The reliability of
intraparenchymal devices has been debated. One group found only a
small (1 mmHg) drift in a group of 163 patients [37]; however, a second
report found that readings varied by >3 mmHg in more than half of the
50 patients studied [38].

Subarachnoid — Subarachnoid bolts are fluid-coupled systems within a

hollow screw that can be placed through the skull adjacent to the dura.
The dura is then punctured, which allows the CSF to communicate with
the fluid column and transducer. The most commonly used subarachnoid
monitor is the Richmond (or Becker) bolt; other types include the Philly
bolt, the Leeds screw, and the Landy screw. These devices have low risk
of infection and hemorrhage, but often clog with debris and are
unreliable; therefore, they are rarely used. Additionally, they are believed
to be less accurate than ventricular ICP devices [30].

Epidural — Epidural monitors contain optical transducers that rest

against the dura after passing through the skull. They often are
inaccurate, as the dura damps the pressure transmitted to the epidural
space, and thus are of limited clinical utility [30,39]. They are used in the
management of coagulopathic patients with hepatic encephalopathy
complicated by cerebral edema. In this setting, use of these catheters is
associated with a significantly lower risk of intracerebral hemorrhage (4
versus 20 and 22 percent for intraparenchymal and intraventricular
devices) and fatal hemorrhage (1 versus 5 and 4 percent, respectively)
[40]. (See "Acute liver failure in adults: Management and prognosis".)

Waveform analysis — ICP is not a static value; it exhibits cyclic variation

based on the superimposed effects of cardiac contraction, respiration,
and intracranial compliance. Under normal physiologic conditions, the
amplitude of the waveform is often small, with B waves related to
respiration and smaller C waves (or Traube-Hering-Mayer waves) related
to the cardiac cycle [10].

Pathological A waves (also called plateau waves) are abrupt, marked

elevations in ICP of 50 to 100 mmHg, which usually last for minutes to
hours (waveform 1). The presence of A waves signifies a loss of
intracranial compliance, and heralds imminent decompensation of
autoregulatory mechanisms [10,41,42]. Thus, the presence of A waves
should suggest the need for urgent intervention to help control ICP.

Noninvasive systems — A number of devices designed to record ICP

noninvasively have been studied, but most have not demonstrated
reproducible clinical success or have been studied in large clinical trials.
We do not use these in clinical practice.

Tissue resonance analysis (TRA), an ultrasound-based method, has

shown some promise. In one trial 40 patients underwent both
invasive and TRA ICP monitoring, with good correlation between
concomitant invasive and TRA measurements [43].
Ocular sonography can provide a noninvasive measure of optic
nerve sheath diameter, which has been found to correlate with
intracranial pressure. A number of studies have found that
diameters of 5 to 6 mm have the ability to discriminate between
normal and elevated ICP in patients with intracranial hemorrhage
and traumatic brain injury [44-50].
Transcranial Doppler (TCD) measures the velocity of blood flow in
the proximal cerebral circulation. TCD can be used to estimate ICP
based on characteristic changes in waveforms that occur in
response to increased resistance to cerebral blood flow [51,52].
 Generally, TCD is a poor predictor of ICP, although in trauma
patients TCD findings may correlate with outcome at six months
[53-55].
Intraocular pressure can be assessed noninvasively using an
ultrasonic handheld optic tonometer. While some evidence suggests
that intraocular pressure correlates with ICP in the absence of
oculofacial trauma or glaucoma [56], most other studies' findings
disagree [57-59].
Tympanic membrane displacement (measured using an impedance
audiometer) has been compared to direct monitoring, based on the
hypothesis that increased ICP will transmit a pressure wave to the
tympanic membrane via the perilymph [60,61].

Advanced neuromonitoring — In order to supplement ICP monitoring,

several technologies have recently been developed for the treatment of
severe TBI. These techniques allow for the measurement of cerebral
physiologic and metabolic parameters related to oxygen delivery,
cerebral blood flow, and metabolism with the goal of improving the
detection and management of secondary brain injury. These are
discussed separately. (See "Management of acute severe traumatic brain
injury", section on 'Advanced neuromonitoring'.)

GENERAL MANAGEMENT — The best therapy for intracranial

hypertension (ICH) is resolution of the proximate cause of elevated ICP.
Examples include: evacuation of a blood clot, resection of a tumor, CSF
diversion in the setting of hydrocephalus, or treatment of an underlying
metabolic disorder.

Regardless of the cause, ICH is a medical emergency, and treatment

should be undertaken as expeditiously as possible. In addition to
definitive therapy, there are maneuvers that can be employed to reduce
ICP acutely. Some of these techniques are generally applicable to all
patients with suspected ICH; others (particularly glucocorticoids) are
reserved for specific causes of ICH.

Resuscitation — The urgent assessment and support of oxygenation,

blood pressure, and end-organ perfusion are particularly important in
trauma, but applicable to all patients [62-64]. If elevated ICP is
suspected, care should be taken to minimize further elevations in ICP
during intubation through careful positioning, appropriate choice of
paralytic agents (if required), and adequate sedation. Pretreatment with
lidocaine has been suggested as a useful intervention to decrease the
rise in ICP associated with intubation; however, good clinical evidence
supporting this approach is limited [65]. (See "Overview of inpatient
management in the adult trauma patient" and "Advanced cardiac life
support (ACLS) in adults" and "Basic life support (BLS) in adults".)
Large shifts in blood pressure should be minimized, with particular care
taken to avoid hypotension. Although it might seem that lower BP would
result in lower ICP, this is not the case. Hypotension, especially in
conjunction with hypoxemia, can induce reactive vasodilation and
elevations in ICP. As noted above, pressors have been shown to be safe
for use in most patients with intracranial hypertension, and may be
required to maintain CPP >60 mmHg [20]. (See "Use of vasopressors
and inotropes".)

Urgent situations — Life-saving measures may need to be instituted prior

to a more detailed workup (eg, imaging or ICP monitoring) in a patient
who presents acutely with history or examination findings suggestive of
elevated ICP. Many of these situations will rely upon clinical judgment,
but the following combination of findings suggests the need for urgent
intervention [66,67]:

A history that suggests elevated ICP (eg, head trauma, sudden

severe headache typical of subarachnoid hemorrhage)
An examination that suggests elevated ICP (unilateral or bilaterally
fixed and dilated pupil(s), decorticate or decerebrate posturing,
bradycardia, hypertension and/or respiratory depression)
A Glasgow coma scale (GCS) ≤8
Potentially confounding, reversible causes of depressed mental
status, hypotension (SBP <60 mmHg in adults), hypoxemia (PaO2
<60 mmHg), hypothermia (<36ºC), or obvious intoxication are
absent

In such patients osmotic diuretics may be used urgently (see 'Mannitol'

below).

In addition, standard resuscitation techniques should be instituted as

soon as possible:

Head elevation
Hyperventilation to a PCO2 of 26 to 30 mmHg
Intravenous mannitol (1 to 1.5 g/kg)

Concomitant with these measures should be aggressive evaluation of the

underlying diagnosis, including neuroimaging, detailed neurologic
examination, and history gathering. Hyperventilation may be
contraindicated in the setting of traumatic brain injury and acute stroke,
and is discussed separately (see 'Hyperventilation' below). If
appropriate, ventriculostomy is a rapid means of simultaneously
diagnosing and treating elevated ICP.

Monitoring and the decision to treat — If a diagnosis of elevated ICP is

suspected and an immediately treatable proximate cause is not present,
then ICP monitoring should be instituted. The use of ICP monitoring is
associated with decreased mortality in patients with traumatic brain
injury [21]. (See "Management of acute severe traumatic brain injury",
section on 'Intracranial pressure'.)

The type of monitoring device employed should be based on an

assessment of the advantages and disadvantages discussed previously
(figure 5). (See 'ICP monitoring' above.)

The goal of ICP monitoring and treatment should be to keep ICP <20
mmHg [68]. Interventions should be utilized only when ICP is elevated
above 20 mmHg for >5 to 10 minutes. As discussed above, brief
physiologic elevations in ICP may occur in the setting of coughing,
movement, suctioning, or ventilator asynchrony.

Fluid management — In general, patients with elevated ICP do not need

to be severely fluid restricted [69]. Patients should be kept euvolemic
and normo- to hyperosmolar. This can be achieved by avoiding all free
water (including D5W, 0.45 percent (half normal) saline, and enteral free
water) and employing only isotonic fluids (such as 0.9 percent (normal)
saline). Serum osmolality should be kept >280 mOsm/L, and often is
kept in the 295 to 305 mOsm/L range. Hyponatremia is common in the
setting of elevated ICP, particularly in conjunction with subarachnoid
hemorrhage. (See "Causes of hyponatremia in adults" and "Treatment of
hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion
(SIADH) and reset osmostat", section on 'Subarachnoid hemorrhage'.)

Similarly, the value of colloid compared to crystalloid fluid resuscitation

in patients with elevated ICP has been studied, but findings have been
inconclusive with respect to the superior approach [70]. A subgroup
analysis in one large study, however, suggested that in patients with
traumatic brain injury, fluid resuscitation with albumin was associated
with a higher mortality as compared with normal saline [71]. (See
"Management of acute severe traumatic brain injury".)

Hypertonic saline in bolus doses may acutely lower ICP, but further
investigations are required to define a role, if any, for this approach in the
management of elevated intracranial pressure. (See 'Hypertonic saline
bolus' below.)

Sedation — Keeping patients appropriately sedated can decrease ICP by

reducing metabolic demand, ventilator asynchrony, venous congestion,
and the sympathetic responses of hypertension and tachycardia [72].
Establishing a secure airway and close attention to blood pressure allow
the clinician to identify and treat apnea and hypotension quickly.

Propofol has been utilized to good effect in this setting, as it is easily

titrated and has a short half-life, thus permitting frequent neurologic
reassessment. (See "Sedative-analgesic medications in critically ill
adults: Selection, initiation, maintenance, and withdrawal".)

Blood pressure control — In general, BP should be sufficient to maintain

CPP >60 mmHg. As discussed above, pressors can be used safely
without further increasing ICP. This is particularly relevant in the setting
of sedation, when iatrogenic hypotension can occur. Hypertension should
generally only be treated when CPP >120 mmHg and ICP >20 mmHg.

Caution should be taken to avoid CPP <50 mmHg or, as noted above,
normalization of blood pressure in patients with chronic hypertension in
whom the autoregulatory curve has shifted to the right (see
'Autoregulation' above). General issues regarding blood pressure
management following stroke are presented elsewhere. (See
"Antihypertensive therapy to prevent recurrent stroke or transient
ischemic attack".)

Position — Patients with elevated ICP should be positioned to maximize

venous outflow from the head. Important maneuvers include reducing
excessive flexion or rotation of the neck, avoiding restrictive neck taping,
and minimizing stimuli that could induce Valsalva responses, such as
endotracheal suctioning.

Patients with elevated ICP have historically been positioned with the
head elevated above the heart (usually 30 degrees) to increase venous
outflow. It should be noted that head elevation may lower CPP [20,73];
however, given the proven efficacy of head elevation in lowering ICP,
most experts recommend raising the patient's head as long as the CPP
remains at an appropriate level [74].

Fever — Elevated metabolic demand in the brain results in increased

cerebral blood flow (CBF), and can elevate ICP by increasing the volume
of blood in the cranial vault. Conversely, decreasing metabolic demand
can lower ICP by reducing blood flow.

Fever increases brain metabolism, and has been demonstrated to

increase brain injury in animal models [75]. Therefore, aggressive
treatment of fever, including acetaminophen and mechanical cooling, is
recommended in patients with increased ICP. Intracranial hypertension is
a recognized indication for neuromuscular paralysis in selected patients
[76]. (See "Use of neuromuscular blocking medications in critically ill
patients".)

Antiepileptic therapy — Seizures can both complicate and contribute to

elevated ICP [77,78]. Anticonvulsant therapy should be instituted if
seizures are suspected; prophylactic treatment may be warranted in
some cases. There are no clear guidelines for the latter, but examples
include high-risk mass lesions, such as those within supratentorial
cortical locations, or lesions adjacent to the cortex, such as subdural
hematomas or subarachnoid hemorrhage.

SPECIFIC THERAPIES — As mentioned previously, the best treatment of

elevated ICP is to address its underlying cause. If this is not possible, a
series of steps should be instituted to reduce ICP in an attempt to
improve outcome. In all cases, the clinician should bear in mind the
themes of resuscitation, reduction of intracranial volume, and frequent
reevaluation discussed above.

Osmotic therapy and diuresis

Mannitol — Osmotic diuretics reduce brain volume by drawing free water

out of the tissue and into the circulation, where it is excreted by the
kidneys, thus dehydrating brain parenchyma [79-82]. The most
commonly used agent is mannitol. It is prepared as a 20 percent
solution, and given as a bolus of 1 g/kg. Repeat dosing can be given at
0.25 to 0.5 g/kg as needed, generally every six to eight hours. Use of any
osmotic agent should be carefully evaluated in patients with renal
insufficiency.

The effects are usually present within minutes, peak at about one hour,
and last 4 to 24 hours [29,83]. Some have reported a "rebound" increase
in ICP; this probably occurs when mannitol, after repeated use, enters
the brain though a damaged blood-brain barrier and reverses the
osmotic gradient [84,85]. Useful parameters to monitor in the setting of
mannitol therapy include serum sodium, serum osmolality, and renal
function.

Concerning findings associated with the use of mannitol include serum

sodium >150 meq, serum osmolality >320 mOsm, or evidence of
evolving acute tubular necrosis (ATN). In addition, mannitol can lower
systemic BP, necessitating careful use if associated with a fall in CPP.
Patients with known renal disease may be poor candidates for osmotic
diuresis. (See "Complications of mannitol therapy".)

Hypertonic saline bolus — Hypertonic saline in bolus doses may acutely

lower ICP; however, the effect of this early intervention on long-term
clinical outcomes remains unclear [86-93]. The volume and tonicity of
saline (7.2 to 23.4 percent) used in these reports have varied widely. As
an example, one controlled trial randomly assigned 226 patients with
traumatic brain injury to prehospital resuscitation with 250 mL
hypertonic saline (7.5 percent) or the same volume of Ringer's lactate
[86]. Survival until hospital discharge, six-month survival, and neurologic
function six months after injury were similar in both groups.
Mannitol and hypertonic saline have been compared in at least five
randomized trials of patients with elevated ICP from a variety of causes
(traumatic brain injury, stroke, tumors) [93-97]. A meta-analysis of these
trials found that hypertonic saline appeared to have greater efficacy in
managing elevated ICP, but clinical outcomes were not examined [98].
Further clinical trials are required to clarify the appropriate role of
hypertonic saline infusion versus mannitol in the management of
elevated ICP [99,100].

The role of hypertonic saline in the management of elevated ICP in

traumatic brain injury is discussed separately. (See "Management of
acute severe traumatic brain injury", section on 'Osmotic therapy'.)

Other agents — Furosemide, 0.5 to 1.0 mg/kg intravenously, may be

given with mannitol to potentiate its effect. However, this effect can also
exacerbate dehydration and hypokalemia [101-103].

Glycerol and urea were used historically to control ICP via

osmoregulation; however, use of these agents has decreased because
equilibration between brain and plasma levels occurs more quickly than
with mannitol. Furthermore, glycerol has been shown to have a
significant rebound effect and to be less effective in ICP control
[104,105].

Glucocorticoids — Glucocorticoids were associated with a worse

outcome in a large randomized clinical trial of their use in moderate to
severe head injury [106,107]. They should not be used in this setting.
(See "Management of acute severe traumatic brain injury".)

In addition, glucocorticoids are not considered to be useful in the

management of cerebral infarction or intracranial hemorrhage. (See
"Spontaneous intracerebral hemorrhage: Treatment and prognosis".)

In contrast, glucocorticoids may have a role in the setting of intracranial

hypertension caused by brain tumors and CNS infections. (See
"Management of vasogenic edema in patients with primary and
metastatic brain tumors" and "Treatment and prognosis of bacterial
brain abscess" and "Dexamethasone to prevent neurologic complications
of bacterial meningitis in adults".)

Hyperventilation — Use of mechanical ventilation to lower PaCO2 to 26

to 30 mmHg has been shown to rapidly reduce ICP through
vasoconstriction and a decrease in the volume of intracranial blood; a 1
mmHg change in PaCO2 is associated with a 3 percent change in CBF
[108]. Hyperventilation also results in respiratory alkalosis, which may
buffer post-injury acidosis [108]. The effect of hyperventilation on ICP is
short-lived (1 to 24 hours) [109-111]. Following therapeutic
hyperventilation, the patient's respiratory rate should be tapered back to
normal over several hours to avoid a rebound effect [112].

Therapeutic hyperventilation should be considered as an urgent

intervention when elevated ICP complicates cerebral edema, intracranial
hemorrhage, and tumor. Hyperventilation should not be used on a
chronic basis, regardless of the cause of increased ICP.

Hyperventilation should be minimized in patients with traumatic brain

injury or acute stroke. In these settings, vasoconstriction may cause a
critical decrease in local cerebral perfusion and worsen neurologic injury,
particularly in the first 24 to 48 hours [24,109,111,113-116]. Thus, the
need for hyperventilation should be carefully considered, and
prophylactic hyperventilation in the absence of elevated ICP should be
avoided. (See "Management of acute severe traumatic brain injury",
section on 'Hyperventilation'.)

Barbiturates — The use of barbiturates is predicated on their ability to

reduce brain metabolism and cerebral blood flow, thus lowering ICP and
exerting a neuroprotective effect [117-120]. Pentobarbital is generally
used, with a loading dose of 5 to 20 mg/kg as a bolus, followed by 1 to 4
mg/kg per hr [121,122]. Treatment should be assessed based on ICP,
CPP, and the presence of unacceptable side effects. Continuous EEG
monitoring is generally used; EEG burst suppression is an indication of
maximal dosing.

The therapeutic value of this maneuver is somewhat unclear. In a

randomized trial of 73 patients with elevations in ICP refractory to
standard therapy, patients treated with pentobarbital were 50 percent
more likely to have their ICP controlled. However, there was no difference
in clinical outcomes between groups [123]. In general, the use of
barbiturates is a "last-ditch" effort, as several studies show that their
ability to lower ICP does not appear to affect outcomes [108,124].

Barbiturate therapy can be complicated by hypotension, possibly

requiring vasopressor support. The use of barbiturates is also associated
with a loss of the neurologic examination, requiring accurate ICP,
hemodynamic, and often EEG monitoring to guide therapy. In this setting,
thiopental has been reported to produce hypokalemia with induction and
rebound hyperkalemia on drug cessation [125].

Therapeutic hypothermia — First reported as a treatment for brain injury

in the 1950s, induced or therapeutic hypothermia has remained a
controversial issue in the debate concerning the management of elevated
ICP [108,126,127]. It is not currently recommended as a standard
treatment for increased intracranial pressure in any clinical setting.
Hypothermia decreases cerebral metabolism and may reduce CBF and
ICP. Initial studies of hypothermia were limited by systemic side effects,
including cardiac arrhythmias and severe coagulopathy. However, later
work suggested that hypothermia can lower ICP and may improve
patient outcomes [128]. Hypothermia also appeared to be effective in
lowering ICP after other therapies have failed [129,130].

Hypothermia can be achieved using whole body cooling, including lavage

and cooling blankets, to a goal core temperature of 32 to 34ºC. The best
method of cooling (local versus systemic), the optimal target core
temperature, and the appropriate duration of treatment are not known
[131]. It appears that rewarming should be accomplished over a period
of less than 24 hours [132].

The value of therapeutic hypothermia has been best assessed in patients

after traumatic brain injury (TBI), but it’s role has not been well
established in that setting. (See "Management of acute severe traumatic
brain injury", section on 'Induced hypothermia' and "Elevated
intracranial pressure (ICP) in children", section on 'Contraindicated
therapies'.)

Given the uncertainties surrounding the appropriate use of therapeutic

hypothermia in patients with elevated ICP, this treatment should be
limited to clinical trials, or to patients with intracranial hypertension
refractory to other therapies.

Removal of CSF — When hydrocephalus is identified, a ventriculostomy

should be inserted (figure 6). Rapid aspiration of CSF should be avoided
because it may lead to obstruction of the catheter opening by brain
tissue. Also, in patients with aneurysmal subarachnoid hemorrhage,
abrupt lowering of the pressure differential across the aneurysm dome
can precipitate recurrent hemorrhage.

CSF should be removed at a rate of approximately 1 to 2 mL/minute, for

two to three minutes at a time, with intervals of two to three minutes in
between until a satisfactory ICP has been achieved (ICP <20 mmHg) or
until CSF is no longer easily obtained. Slow removal can also be
accomplished by passive gravitational drainage through the
ventriculostomy. A lumbar drain is generally contraindicated in the
setting of high ICP due to the risk of transtentorial herniation.

Decompressive craniectomy — Decompressive craniectomy removes the

rigid confines of the bony skull, increasing the potential volume of the
intracranial contents and circumventing the Monroe-Kellie doctrine.
There is a growing body of literature supporting the efficacy of
decompressive craniectomy in certain clinical situations [133-142].
Importantly, it has been demonstrated that in patients with elevated ICP,
craniectomy alone lowered ICP 15 percent, but opening the dura in
addition to the bony skull resulted in an average decrease in ICP of 70
percent [143]. Decompressive craniectomy also appears to improve
brain tissue oxygenation [144].

Observational data suggest that rapid and sustained control of ICP,

including the use of decompressive craniectomy, improves outcomes in
trauma, stroke, and subarachnoid hemorrhage in carefully selected cases
[145-152]. The indications for decompressive craniectomy in these
settings are discussed separately. (See "Decompressive hemicraniectomy
for malignant middle cerebral artery territory infarction" and
"Management of acute severe traumatic brain injury", section on
'Decompressive craniectomy'.) Obvious mass lesions associated with an
elevated ICP should be removed, if possible.

Potential complications of surgery include herniation through the skull

defect, spinal fluid leak, wound infection, and epidural and subdural
hematoma [153].

Paradoxical transtentorial herniation is an uncommon but potentially

lethal complication in patients with hemicraniectomy and a large skull
defect who subsequently undergo lumbar puncture (LP) or CSF drainage
[154,155]. This results from the combined effects of atmospheric
pressure with the negative pressure of the LP or ventriculostomy. It has
also been described as a delayed complication three to five months after
decompressive craniectomy for cerebral infarction in the absence of LP
or ventriculostomy [156]. Marked decompression of the skin and dura
over the skull defect accompany and may precede neurologic signs of
herniation. Standard treatments to lower ICP can hasten herniation.
Instead, the patient should be placed supine or in the Trendelenburg
position, CSF drains should be clamped, crystalloid fluid should be
administered intravenously, and an epidural blood patch placed for
patients with dural leak.

SUMMARY — The best therapy for intracranial hypertension is resolution

of the proximate cause of elevated ICP. Regardless of the cause,
treatment should be undertaken as expeditiously as possible, and should
be based on the principles of resuscitation, reduction of the volume of
the intracranial contents, and reassessment. The role of evidence-based
guidelines in the clinical management of elevated ICP is evolving [157].
However, it is important to remember that individual patients respond
differently to different therapies; therefore, interventions should be based
on careful assessment of the individual clinical scenario rather than on
strict protocols.
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Topic: 1659 Version: 9.0

Release: 22.10 - C23.10