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Evaluation and management of elevated intracranial pressure in adults

Authors Section Editor Deputy Editor

Edward R Smith, MD Michael J Aminoff, MD, DSc Janet L Wilterdink, MD
Sepideh Amin-Hanjani, MD

Contributor disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2016. | This topic last updated: Jul 10, 2013.

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 (<36C), 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 34C. 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 its 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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