ANALYTIC REVIEWS

Critical Care Management of Increased

Intracranial Pressure
Stephan A. Mayer, MD*
and Ji Y. Chong, MD*
Mayer SA, Chong JY. Critical care management of increased
intracranial pressure. J Intensive Care Med 2002;17:5567.

Increased intracranial pressure (ICP) is a pathologic state

common to a variety of serious neurologic conditions, all of
which are characterized by the addition of volume to the
intracranial vault. Hence all ICP therapies are directed toward
reducing intracranial volume. Elevated ICP can lead to brain
damage or death by two principle mechanisms: (1) global
hypoxic-ischemic injury, which results from reduction of
cerebral perfusion pressure (CPP) and cerebral blood ow,
and (2) mechanical compression, displacement, and herniation of brain tissue, which results from mass effect
associated with compartmentalized ICP gradients. In
unmonitored patients with acute neurologic deterioration,
head elevation (30 degrees), hyperventilation (pCO2 2630
mmHg), and mannitol (1.01.5 g/kg) can lower ICP within
minutes. Fluid-coupled ventricular catheters and intraparenchymal pressure transducers are the most accurate and
reliable devices for measuring ICP in the intensive care unit
(ICU) setting. In a monitored patient, treatment of critical ICP
elevation (>20 mmHg) should proceed in the following steps:
(1) consideration of repeat computed tomography (CT)
scanning or consideration of denitive neurosurgical intervention, (2) intravenous sedation to attain a quiet, motionless
state, (3) optimization of CPP to levels between 70 and 110
mmHg, (4) osmotherapy with mannitol or hypertonic saline,
(5) hyperventilation (pCO2 2630 mmHg), (6) high-dose
pentobarbital therapy, and (7) systemic cooling to attain
moderate hypothermia (3233C). Placement of an ICP
monitor and use of a stepwise treatment algorithm are both
essential for managing ICP effectively in the ICU setting.

From the Division of Critical Care Neurology, Departments of

*Neurology and Neurosurgery, College of Physicians and
Surgeons, Columbia University, New York, NY.
Received Jul 30, 2001, and in revised form Aug 24, 2001. Accepted
for publication Aug 28, 2001.
Address correspondence to Dr. Mayer, Neurological Institute,
710 West 168th St., Unit 39, New York, NY 10032, or e-mail:
sam14@columbia.edu.

Increased intracranial pressure (ICP) can result

from a number of insults to the brain, including
traumatic brain injury (TBI), stroke, encephalitis,
neoplasms, and abscesses (Table 1). The fundamental abnormality common to these diverse
disease states is an increase in intracranial volume.
Accordingly, all treatments for elevated ICP work by
reducing intracranial volume. Prompt recognition
and treatment of elevated ICP is essential because
sustained elevated ICP can cause brain damage or
be rapidly fatal.

Pathophysiology
Intracranial Compliance. The MonroeKellie
doctrine dictates that the cranial vault is a xed
space that contains three compartments: blood,
cerebrospinal uid (CSF), and brain tissue. In the
average adult, the brain volume is 1400 ml, the
blood volume is 150 ml, and the CSF volume is 150
ml. CSF is produced by the choroid plexus in the
ventricles at a rate of approximately 20 ml/hr, and
drains into the venous system via the arachnoid villi
and granulations [1]. This outow is normally of low
resistance; hence jugular venous pressure is the
chief determinant of ICP in healthy patients. Normal
ICP ranges from 50 to 200 mmH2O or 315 mmHg.
In routine intensive care unit (ICU) practice, the
goal of ICP management is to maintain levels below
20 mmHg.
In pathologic states characterized by increased
ICP (Table 1), additional volume is added to the
intracranial compartment. This can result from the
addition of an extrinsic mass lesion or from an
increase in the volume of CSF (hydrocephalus),
brain tissue (cytotoxic edema), or blood (vasogenic
edema). To maintain ICP within normal limits, these
increases in intracranial volume are initially counterbalanced by volume reductions in the other
compartments. CSF is displaced through the foramen magnum into the paraspinal space, blood is
displaced from the intracranial to the extracranial
venous system, and the brain parenchyma is compressed. After these mechanisms are exhausted,
Copyright 2002 Blackwell Science, Inc. 55

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Journal of Intensive Care Medicine Vol 17 No 2 March/April 2002

Table 1. Conditions Associated with Increased ICP

Intracranial mass lesions
Subdural hematoma
Epidural hematoma
Brain tumor
Cerebral abscess
Intracerebral hemorrhage
Increased brain volume (cytotoxic edema)
Cerebral infarction
Global hypoxia-ischemia
Reye's syndrome
Acute hyponatremia
Increased blood and brain volume (vasogenic edema)
Hepatic encephalopathy
Traumatic brain injury
Meningitis
Encephalitis
Hypertensive encephalopathy
Eclampsia
Subarachnoid hemorrhage
Dural sinus thrombosis
Altitude-related cerebral edema
Increased CSF volume
Communicating hydrocephalus
Noncommunicating hydrocephalus
Choroid plexus papilloma

intracranial compliance (DV/DP) falls sharply, and

even small increases in intracranial volume can lead
to dramatic elevations in ICP (Fig 1).
The relative state of intracranial compliance can
be assessed by inspection of the ICP waveform
(Fig 1, insets). ICP normally increases 23 mmHg
with each arterial pulse because of transient increases in cerebral blood volume (CBV). When intracranial compliance is reduced, intracranial pulse
pressure can reach levels of 1015 mmHg, which
reects loss of the ability to accommodate even
small pulsatile increases in CBV. As intracranial
compliance falls, the morphology of the ICP
waveform also changes, in that the amplitude of
the second peak (the dicrotic wave) initially equals
and then exceeds the amplitude of the rst peak
(the percussion wave) (Fig 2).
Cerebral Perfusion Pressure. Cerebral perfusion pressure (CPP), dened as the mean arterial
pressure (MAP) minus ICP, is a critical determinant
of cerebral blood ow (CBF) and plays an important role in ICP management. Normally CBF is
``autoregulated'' at a constant level over a wide
range of CPPs (from 50 to 150 mmHg) (Fig 3).
Pressure autoregulation of this type is mediated by
changes in arteriolar diameter and cerebrovascular
resistance. The autoregulatory curve is shifted to the
left in children and shifted to the right in patients
with chronic hypertension. In pathologic states
with impaired autoregulation, such as TBI and

Fig 1. Intracranial pressure-volume relationship. At

point A, on the at portion of the curve, the amplitude of
the arterial reection in the ICP waveform is small (inset),
and the addition of volume leads to a small increase, in
pressure (A). At point B, on a steeper portion of the curve,
the intracranial compartment is relatively noncompliant,
the amplitude of the arterial reection in the ICP waveform is large (inset), and addition of the same amount of
volume leads to a larger increase, in pressure (B). (Reprinted from Mayer SA. Management of increased intracranial pressure. In: Wijdicks EFM, Diringer MN, Bolton
CF, et al. Continuum: Critical Care. Minneapolis, MN:
American Academy of Neurology, 1997:4761.)

Fig 2. ICP waveform in conditions of normal (top) and

abnormal (bottom) intracranial compliance. (Reprinted
from Chestnut RM, Marshall LF. Treatment of abnormal
intracranial pressure. Neurosurg Clin N Am 1991;2:267
284.)

subarachnoid hemorrhage, CBF may approximate a

linear relationship with CPP, which creates a
smaller range of optimal CPP (Fig 2). Reduction of
CPP below the lower limit of autoregulation can
lead to ischemia [2], whereas CPP elevation above
the upper limit of autoregulation can be associated
with hyperemia, exacerbation of vasogenic edema,
and increased ICP [3]. Although the optimal CPP for
any particular patient may vary, as a rule of thumb

Mayer and Chong: Management of ICP

Fig 3. Cerebral autoregulation curve. In the normal

relationship (solid line), with CBF held constant across a
wide range of CPP (50150 mmHg). In disease states (e.g.,
vasospasm, ischemia, intracranial mass lesion), cerebral
blood ow may become pressure passive (dotted line).
(Reprinted from Mayer SA. Management of increased
intracranial pressure. In: Wijdicks EFM, Diringer MN,
Bolton CF, et al. Continuum: Critical Care. Minneapolis,
MN: American Academy of Neurology, 1997:4761.)

CPP should be maintained above 70 mmHg to avert

ischemia, and below 110 mmHg to avoid breakthrough hyperperfusion. To accurately measure
CPP in the ICU, the pressure transducer used to
measure MAP must be set at head level [4].
CBF also depends upon PaCO2 and PaO2 levels.
In general, the cerebral vessels are less responsive
to changes in PaO2 than to those in PaCO2.
Arteriolar diameter and CBF progressively increase
as PaCO2 rises from 20 to 80 mmHg, whereas
hypoxemia leads to vasodilation and increased CBF
only when PaO2 falls below 50 mmHg [1].
Pathologic ICP Waves. Patients with reduced
intracranial compliance and elevated ICP may
develop pathologic ICP waves (Fig 4). Lundberg
A waves (plateau waves) are dangerous elevations
in ICP [5]. They occur suddenly, can reach levels of
50100 mmHg, and can last from minutes to hours.
Plateau waves are characteristically associated with
``mirror'' reductions in CPP (Fig 5). When severe,
plateau waves are associated with reduced CPP and
CBF, leading to global hypoxic-ischemic damage.
Lundberg B waves are of lesser amplitude (520
mmHg) and of shorter duration (15 minutes) than
A waves. Although they are not directly harmful, B
waves are a useful marker of abnormal intracranial
compliance. Both of these waves characteristically
end with a surge in systemic blood pressure and
ICP, known as a termination spike [5,6].
A vasodilatory cascade model has been proposed
to explain the pathogenesis of pathologic ICP
waves [6,7]. According to this model, pathologic A
and B waves occur because CPP is inadequate. The

57

Fig 4. Pathologic ICP elevations. (A) Lundberg A (plateau) waves. (B) Lundberg B waves. (Reprinted from
Mayer SA. Management of increased intracranial pressure. In: Wijdicks EFM, Diringer MN, Bolton CF, et al.
Continuum: Critical Care. Minneapolis, MN: American
Academy of Neurology, 1997:4761.)

process begins with a reduction in CPP, which

results from a drop in MAP or a surge in ICP [6]. To
maintain CBF, the cerebral vasculature dilates and
CBV increases. This adds volume to the intracranial
compartment, resulting in an increase in ICP and
further reduction of CPP. This initiates a vicious
cycle in which cerebral vasodilation continues until
it is maximal, at which point a ``plateau'' is reached
at a new level of increased CBV and ICP and
decreased CPP and CBF. The plateau ends once
CBF is inadequate to maintain tissue oxygenation
and ischemia develops. This results in a reex
systemic pressor response mediated by a surge in
systemic vascular resistance. MAP climbs and CPP is
restored (the termination spike), which allows the

Fig 5. Plateau waves followed by sustained ICP elevation in a patient with traumatic brain injury. Early in the
course of the recording, plateau waves exceeding 90
mmHg are associated with ``mirror'' reductions in CPP
below 50 mmHg. At the end of the recording, ICP remains
elevated between 40 and 60 mmHg, MAP falls below 75
mmHg, and CPP drops to 20 mmHg. At this point the
patient became clinically brain dead.

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Journal of Intensive Care Medicine Vol 17 No 2 March/April 2002

cerebral vessels to return to normal caliber, restoring CBV and ICP to normal levels.

Signs of Increased ICP and Herniation

The clinical manifestations of increased ICP are well
known, but are notoriously unreliable (Table 2). A
depressed level of consciousness and reex hypertension, the two most consistent signs, both reect
the effects of globally reduced CBF. However, many
patients have multiple reasons for a depressed level
of consciousness, and in some patients with signicant shift and mass effect, ICP may be normal.
Comatose patients with intracerebral hemorrhage
[8] and middle cerebral artery territory infarction [9],
for instance, may have ICP levels that vary from
normal to highly elevated, and brain stem herniation can occur in the absence of elevated ICP.
Cushing's triad (hypertension, bradycardia, and
irregular respiration), which was originally described in response to elevated ICP, can also result
from brain stem herniation. Because of the poor
correlation between clinical signs and ICP, the only
way to properly diagnose increased ICP is to
directly measure it.
It is important to differentiate clinical signs of
increased ICP from signs of cerebral herniation
(Table 3). Brain tissue displacement and herniation
occur when compartmentalized mass effect leads to
ICP gradients [10,11]. Patients with intracranial mass
Table 2. Clinical Signs of Increased ICP
Signs which are almost always present
Depressed level of consciousness
(lethargy, stupor, oma)
Hypertension, with or without bradycardia
Symptoms and signs which are sometimes present
Headache
Vomiting
Papilledema
Sixth cranial nerve palsies

lesions may have elevated ICP, brain tissue shifting,

or both. Herniation is often rapidly fatal, but can be
reversed by reducing mass effect related to
compartmentalized ICP gradients with treatments
such as mannitol, hypertonic saline, and hyperventilation.

ICP Monitoring
Indications. Invasive monitoring of ICP is generally indicated in patients who meet all three of the
following criteria:
1. The patient is suspected to be at risk for elevated
ICP.
2. The patient is comatose (Glasgow coma scale
score 8).
3. The prognosis is such that aggressive ICU treatment is indicated.
Suspicion of increased ICP is usually based on
clinical signs (Tables 2 and 3) and the results of a
computed tomography (CT) scan showing signicant intracranial mass effect with midline shift or
effacement of the basal cisterns. However, in
comatose patients with TBI, intracranial hypertension occurs in approximately 10% of patients with
normal CT scans; this risk is even higher in patients
more than 40 years old, with motor posturing, or
with hypotension (systolic blood pressure < 90
mmHg) [12].
If a patient is awake and can follow commands, it
is unlikely that ICP is dangerously elevated [13], and
the benets of ventricular drainage or ICP monitoring probably do not outweigh the risks. Careful
monitoring of mental status in an ICU will usually
sufce in these cases.
Invasive ICP monitoring devices. Empiric therapy for increased ICP (i.e., standing doses of mannitol) without invasive monitoring is a distressingly
common practice. This approach is unsatisfactory

Table 3. Herniation Syndromes

Type

Clinical hallmark

Causes

Uncal (lateral transtentorial)

Ipsilateral CN 3 palsy
Contralateral motor posturing

Temporal lobe mass lesion

Central transtentorial

Coma with progression from bilateral

decorticate to decerbrate posturing
Rostral-caudal loss of brain stem reexes

Diffuse cerebral edema

Acute hydrocephalus

Subfalcine

Coma with asymmetric

(contralateral > ipsilateral) motor posturing

Convexity (frontal or parietal)

mass lesion

Cerebellar
(upward or downward)

Sudden progression to coma with bilateral

motor posturing in a patient with cerebellar signs

Cerebellar mass lesion

Mayer and Chong: Management of ICP

because most ICP treatments are effective for a short

time only, may lose their efcacy with prolonged
use, and have side effects. Optimally therapy
should be given when ICP is high, and withheld
when it is normal. Only an invasive ICP monitor
makes this possible. The four main types of invasive
ICP monitors used in standard ICU practice are
listed below, in general order of their accuracy and
reliability (Fig 6).
INTRAVENTRICULAR CATHETERS. These devices directly
connect the intracranial space to an external
pressure transducer via saline-lled tubing. The
bedside pressure transducer must be positioned at
the level of the foramen of Monroe (external
auditory meatus) to accurately reect ICP. The
catheter is usually connected to both a pressure
transducer and an external drainage system via a
three-way stopcock. The system can then be set for
continuous ICP monitoring with intermittent CSF
drainage or continuous drainage with intermittent
ICP measurement. The major advantage to intraventricular catheters (IVCs) is that they allow
treatment of increased ICP via drainage of CSF.
The main disadvantage is the high risk of infection
(ventriculitis or meningitis), which occurs in
1020% of patients and increases dramatically after
5 days [14]. Most neurointensivists administer
prophylactic antibiotics with gram-positive coverage, such as oxacillin 12 g every 6 hours, to
minimize this risk. In a clinical trial of 228 IVC
patients, prolonged therapy with ampicillin sulbactam in the ICU signicantly reduced the frequency
of CSF infection compared to patients given perioperative treatment only (3% versus 11%) [15].

Fig 6. ICP monitoring devices. (A) Intraparenchymal

beroptic probe or microsensor; (B) intraventricular
catheter; (C) epidural transducer; (D) subarachnoid bolt.
(Reprinted from Mayer SA. Management of increased
intracranial pressure. In: Wijdicks EFM, Diringer MN,
Bolton CF, et al. Continuum: Critical Care. Minneapolis,
MN: American Academy of Neurology, 1997:55.)

59

INTRAPARENCHYMAL PRESSURE TRANSDUCERS. The pressure transducer in these disposable devices is

incorporated into the tip of a thin beroptic cable
(the Camino device) or within a strain-gauge
microsensor at the tip of a exible catheter (the
Codman device). These catheters can be placed into
either the brain parenchyma or the ventricle via a
small burr hole and screw [16,17]. With intraparenchymal placement, the infection rate is exceedingly
low (approximately 1%) [18]. When combined with
a ventricular catheter, the system allows simultaneous CSF drainage and continuous ICP measurement. These devices only need to be calibrated
once prior to insertion, and the accuracy of ICP
measurements is generally superior to those provided by subarachnoid bolts or epidural transducers
[19]. A new version of the Codman monitor also
provides measurements of brain temperature. A
third parenchymal monitor recently approved by
U.S. Food and Drug Administration (FDA) (the
Spielberg device) features a small air-lled balloon
at the tip of a exible catheter; it has the advantage
of providing measurements of intracranial compliance (calculated as a pressure/volume index) as
well as ICP [20].
SUBARACHNOID BOLTS. This is another uid-coupled
system which connects the intracranial space to an
external transducer at the bedside via saline-lled
tubing [21]. The subarachnoid bolt is actually a
hollow screw that is inserted via a burr hole. The
dura at the base of the bolt is perforated with a
spinal needle, allowing the subarachnoid CSF to ll
the bolt. Pressure tubing is then connected to
establish communication with a pressure monitoring system. Although the infection risk is low, these
devices are prone to error, including underestimation of ICP, screw displacement, and occlusion by
debris [22].
EPIDURAL TRANSDUCERS. These devices (the Gaeltec
device) are inserted deep into the inner table of the
skull and supercial to the dura [23]. In most of these
devices, pressure is transduced by an optical sensor.
They have a low infection rate (approximately 1%)
[17], but are prone to malfunction, displacement,
and baseline drift that can exceed 510 mmHg after
more than a few days of use. Much of the inaccuracy
results from having the relatively inelastic dura
between the sensor tip and the subarachnoid space.

Noninvasive ICP Monitoring. At present there is

no noninvasive method that can provide accurate
continuous on-line measurement of ICP. However,
transcranial Doppler (TCD) ultrasonography,
which measures the velocity of blood ow in the

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Journal of Intensive Care Medicine Vol 17 No 2 March/April 2002

basal cerebral arteries, shows characteristic changes

with increasing ICP [24]. As CPP falls, diastolic
velocity decreases and pulsatility increases, reecting increased distal vascular resistance to ow.
Though this nding is specic for severe intracranial hypertension, TCD is not sensitive to mild to
moderate ICP elevations. Lateralized asymmetries
in TCD pulsatility correlate with lesion volume in
intracerebral hemorrhage, and are believed to
reect compartmentalized ICP gradients [25]. Promising new applications using ultrasound technology
to estimate ICP noninvasively have been described,
but have not yet been validated in the clinical setting
[2628].
Adjuncts to ICP Monitoring. Several new
modalities have recently been introduced that can
provide additional information regarding the adequacy of cerebral perfusion and the extent of
injury in patients undergoing ICP monitoring.
JUGULAR VENOUS OXYGEN SATURATION (SJVO2) AND

BRAIN TISSUE PO2 (PBTO2) MONITORING. SjvO2 monitoring assesses the adequacy of global cerebral
oxygen delivery, whereas PbtO2 monitoring measures regional oxygen tension. Both emerging
technologies provide continuous information regarding the adequacy of CPP and CBF at the tissue
level [2931]. SjvO2 is measured with a 5-French
beroptic oxygen saturation catheter placed retrograde in the internal jugular vein so that the tip is
positioned in the jugular bulb; PbtO2 is measured
with a miniaturized Clark electrode embedded in
the tip of a thin catheter inserted 34 cm into the
cerebral white matter (the Licox or Neurotrend
device). Both techniques can detect inadequate
CBF (i.e., ischemia), which may occur even in
patients with relatively normal CPP [32], and
excessive CBF (i.e., hyperemia), which can aggravate ICP related to vasogenic edema and breakthrough of autoregulation [33]. Accordingly these
monitors can be used to optimize therapy: mannitol
and vasopressor infusion reduce ICP and improve
cerebral oxygenation when SjvO2 or PbtO2 values
fall below critical levels [3032], whereas hyperventilation reduces ICP and tissue oxygenation
when it is supranormal due to relative hyperperfusion [31] (Table 4). The depth and duration of
ischemia detected by either device is highly correlated with poor clinical outcome in patients with
severe TBI [30,31]. Since neither monitor alone can
detect all episodes of ischemia [34], selection of
which type to use depends on the specic clinical
circumstances at hand. PbtO2 monitoring is generally easier to use, and is most desirable when
detection of ischemia in a specic brain region is the

Table 4. Normal and Critical Values for SjvO2 and PbtO2

Monitors

Normal valuea
Critical upper limit
(indicates hyperemia)
Critical lower limit
(indicates ischemia)
Average value in severe TBIa

SjvO2
(%)

PbtO2
(mm Hg)

62
80

37
NA

50

73 10

32 19

NA data not available.

Interpretation of critical values assumes normal FiO2 (40%) and
hematocrit.
a
Data from reference 34.

predominant concern, whereas SjvO2 is less inuenced by high FiO2 levels and hence may be a more
reliable measure of relative hyperperfusion [34].
CEREBRAL MICRODIALYSIS. This adjunctive monitoring
technique is labor intensive and has yet to gain
widespread acceptance. A probe is placed through
the skull and levels of different substances may be
measured using high-performance liquid chromatography (HPLC). Lactate, glutamate, and more
recently extracellular potassium have been measured using this microdialysis. These levels correlate
with cerebral ischemia and poor outcome [35].
MULTIMODAL MONITORING. Finally, a combination of
multiple monitoring techniques may soon be
possible. Various prototypes are in development
that can allow simultaneous monitoring of ICP,
PbtO2, PbtCO2, pH, brain temperature, laser Doppler ow, and even microdialysis.

Management of Increased ICP

General Care Issues. Proper management of all
critically ill brain-injured patients begins with
general care issues designed to optimize oxygenation and cerebral blood ow and to minimize
factors that can aggravate neuronal injury or trigger
ICP elevations. The following guidelines should be
followed in all patients at risk for increased ICP:
PATIENT POSITIONING. As long as the patient is not
hypotensive (mean blood pressure < 60 mmHg),
the head of the bed should be elevated to 30
degrees and a straight head position should be
maintained. Head elevation to 30 degrees reduces
ICP by reducing jugular and cerebral venous
pressure and enhancing venous outow, without
signicantly lowering CPP, CBF, or cardiac output
[36,37]. Some have recommended a head at
position to prevent any reductions of CPP that

Mayer and Chong: Management of ICP

may occur with head elevation, which may be

reasonable in selected cases [38]. However, head
elevation in excess of 45 degrees should generally
be avoided because paradoxical increases in ICP
can occur in response to excessive CPP reduction
[39]. Sharp head angulation should also be avoided,
as it may cause jugular venous compression,
increased venous backpressure, and increased ICP.
FLUID MANAGEMENT. Only isotonic uids, such as
0.9% (normal) saline or lactated Ringer's solution,
should be used in patients at risk for elevated ICP.
Cerebral edema is generally understood to result
from the creation of ``idiogenic osmoles'' which
draw water down an osmolar gradient into injured
brain tissue. Hypotonic uids such as 5% dextrose
or 0.45% (half-normal) saline should be strictly
avoided because the free water contained in these
uids can aggravate cerebral edema and increase
ICP [40]. Systemic hypo-osmolality (<280 mOsm/L)
should be aggressively treated with mannitol or 3%
hypertonic saline. The traditional practice of
restricting total uid intake (dehydration therapy),
with the goal of reducing the extracellular uid
volume, has not been shown to signicantly impact
brain water content or ICP. In fact, hypovolemia
may lead to inadequate CPP and a consequent
increase in ICP [41].
Patients with elevated ICP should have a central
venous line placed to monitor central venous
pressure; this is particularly critical for patients
treated with mannitol or hypertonic saline. As a
general rule, a central venous pressure greater than
5 mmHg and equal to slightly positive daily net uid
balance should be maintained by increasing the rate
of infusion of isotonic crystalloid, administering
0.9% saline or 5% albumin uid boluses, or
transfusing blood to maintain hematocrit at greater
than 24% [42].
Use of 1.53% hypertonic saline as a maintenance
intravenous uid for patients with cerebral edema is
gaining popularity in the neurocritical care community. Though support for this practice to date is
inconclusive, adequate clinical trials have yet to be
performed [43]. A small study of pediatric TBI
patients compared the use of 1.6% saline with
lactated Ringer's solution and found no differences
in ICP or CPP, though the hypertonic saline group
required fewer interventions to lower ICP [44]. Lack
of uniform concentrations and poor denition of
dose-response relationships has limited the widespread use of hypertonic saline to date.
TEMPERATURE MANAGEMENT. Fevers should be treated aggressively. Temperature elevations increase
ICP by increasing cerebral metabolism and blood

61

ow, and have been shown to exacerbate hypoxicischemic neuronal injury in experimental animals
[45]. As a general standard, acetaminophen and
cooling blankets should be given to all patients with
sustained fevers in excess of 38.3C (101.0F), but
evidence for their efcacy in neurologic patients is
scant [46,47]. Endovascular cooling with the use of
closed-circuit water-circulating intravenous catheters is a promising new approach that is currently
under development.
Recent studies suggest that indomethacin may be
the ideal antipyretic to use in patients with
increased ICP. Indomethacin has been shown to
decrease CBF and ICP in animal models and
patients with TBI [48]. The mechanism of action is
not known, but may involve vasoconstriction of
cerebral vessels and inhibition of prostaglandin
synthesis [48].
SEIZURE PROPHYLAXIS. Seizures can lead to profound
elevations of CBF, CBV, and ICP, even in patients
who are sedated or paralyzed [49]. This is secondary
to the increased cerebral metabolic demand that
occurs with seizures. Intravenous fosphenytoin
(1520 mg/kg loading dose, 35 mg/kg/day) is
the preferred agent for seizure prophylaxis while in
the ICU.
STEROIDS. Dexamethasone and other steroids
should not be used as a standard treatment for ICP
because they are ineffective against cytotoxic
edema [50]. There is generally no role for steroids
in the treatment of mass effect related to cerebral
infarction [51], intracerebral hemorrhage [52], or TBI
[53]. By contrast, vasogenic edema related to
neoplasm or abscess is steroid responsive, and
dexamethasone 420 mg every 6 hours can lead to
dramatic reductions in lesion volume [54].

Emergent Treatment of Increased ICP in an

Unmonitored Patient. Emergency measures for
ICP control (Table 5) are appropriate for comatose
patients who present acutely with clinical signs of
increased ICP or herniation. These measures are

Table 5. Emergency Measures for ICP Reduction

1. Elevate head of bed 1530 degrees.
2. Normal saline (0.9%) at 80100 cc/hr
(avoid hypotonic uids).
3. Intubate and hyperventilate (target pCO2 2630
mmHg).
4. Mannitol 20% 11.5 g/kg via rapid intravenous
infusion.
5. Foley catheter.
6. CT scan and urgent neurosurgical consultation.

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Journal of Intensive Care Medicine Vol 17 No 2 March/April 2002

designed to lower ICP as quickly and effectively as

possible in order to ``buy time'' before a denitive
neurosurgical procedure (craniotomy, ventriculostomy, or placement of an ICP monitor) can be
performed. Aggressive hyperventilation and mannitol therapy are the cornerstones of this type of
intervention.
Stepwise Treatment Protocol for Elevated ICP
in a Monitored Patient. The primary goal of ICP
management in a monitored patient is to maintain
ICP below 20 mmHg and CPP above 70 mmHg.
Contemporary ICP management has changed in
recent years in two important aspects: CPP management (in addition to ICP control) has become
increasingly emphasized, and the potential for
overzealous hyperventilation to cause excessive
vasoconstriction and aggravate ischemia has
become increasingly recognized. The stepwise
protocol presented here for managing ICP in a
monitored patient (Table 6) reects these considerations. More than one step may be instituted
simultaneously, but only after all of the preceding
steps have been addressed. Likewise, ICP therapy
should be withdrawn in a similar stepwise fashion
(Fig 7). This algorithm should be initiated any time
ICP remains greater than 20 mmHg for more than 10
minutes.
Though we favor the protocol presented below
because of its simplicity, other treatment algorithms
may be equally effective. Use of a standardized,
evidence-based protocol for ICP management allows for efcient and well-coordinated treatment of
patients within an institution, and can improve
patient outcomes. In a retrospective study of
patients with TBI, patients treated with a standardized algorithm of instituting and weaning ICP
therapies required fewer interventions and had a
Table 6. Stepwise Treatment Protocol for Elevated ICPa
in a Monitored Patient
1. Surgical decompression. Consider repeat CT
scanning and denitive surgical intervention or
ventricular drainage.
2. Sedation. Intravenous sedation to attain a
motionless, quiet state.
3. CPP optimization. Pressor infusion if CPP is less than
70 mmHg, or reduction of blood pressure if CPP is
greater than 110 mmHg.
4. Osmotherapy. Mannitol 0.251.0 g/kg intravenously
(repeat every 16 hours as needed).
5. Hyperventilation. Target pCO2 levels of 2630 mmHg.
6. High-dose pentobarbital therapy. Load with 520
mg/kg, infuse 14 mg/kg/hr.
7. Hypothermia. Cool core body temperature to 3233C.
a
More than 20 mmHg for more than 10 minutes.
Refer to text for details.

Fig. 7. The Columbia stepwise protocol for ICP

management.

shorter duration of treatment than patients treated

ad hoc [55].
STEP 1: SURGICAL DECOMPRESSION OR CSF DRAIN-

AGE. The rst consideration in the face of an acute

increase in ICP should always be whether a
denitive intervention, such as craniotomy or
ventriculostomy, should be performed to remove
volume or decompress the skull. A repeat CT scan
should be considered to rule out reaccumulation of
an intracranial hemorrhage or worsening hydrocephalus. If a ventricular catheter is in place, the
system should be opened to drainage and 510 ml
of CSF removed.
The option of some denitive surgical intervention should be continuously evaluated as additional
steps to control ICP are added. Controlled lumbar
CSF drainage (520 ml/hr) has been reported to
reduce ICP and increase CPP in patients refractory
to medical therapy and ventricular drainage alone
[56]. However, this intervention is feasible only if
the basal cisterns are open on CT, and even in these
cases, transtentorial herniation remains a risk.
Decompressive hemicraniectomy is becoming increasingly used as an intervention of last resort for
patients who might otherwise require pentobarbital
or hypothermia. Wide cranial decompression can
denitively control ICP and reverse brain stem
herniation, and has been reported to be effective for
treating massive cerebral infarction [57], encephalitis [58], head trauma [59], and intracerebral hemorrhage [60] in nonrandomized studies. Complications of hemicraniectomy can include CSF leakage,
local wound infection or meningitis, intracranial
bleeding, and late hydrocephalus.
STEP 2: SEDATION. Sedation is often overlooked as a
key factor in ICP control. In patients with reduced
intracranial compliance, ghting against physical
restraints or ``bucking'' the ventilator can increase

Mayer and Chong: Management of ICP

ICP by elevating intrathoracic and jugular venous

pressure. Arterial hypertension associated with
agitation may further increase ICP if the patient is
at the upper range of the autoregulatory curve.
Before further measures are instituted, agitated
patients with increased ICP should be sedated to the
point where they are quiet and motionless (Ramsey
level 5 or 6). A combination of a sedative-hypnotic
and analgesic agent is usually most effective
(Table 7). The preferred regimen is the combination of an opioid, such as fentanyl (13 lg/kg/hr) or
sufentanil (0.10.6 lg/kg/hr), to provide analgesia
and propofol (0.33 mg/kg/hr) for sedation. It is
important to use drugs that are short acting, such
that the agent may be stopped for frequent neurologic assessments throughout the day. One study
showed that daily, scheduled interruption of sedation to examine patients not only reduced the
length of ventilator dependence and ICU length of
stay, but also decreased the need for other tests such
as brain imaging and lumbar punctures to evaluate
alterations in mental status [61].
Neurocritical care patients, even when comatose,
can sense pain and require analgesia in addition to
sedation. Therefore careful use of a low-dose continuous infusion opioid in addition to propofol or
midazolam is recommended. Bolus injections of
opioids, however, should be used with caution in
patients with elevated ICP. Bolus infusions of the
sufentanil, fentanyl, and alfentanil can transiently
lower MAP and increase ICP due to autoregulatory
vasodilation of cerebral vessels [62]. This effect is
seen primarily in patients with intact autoregulation,
but can also occur in patients with abnormal autoregulation [63]. Vasopressors may be used to avoid
hypotension and possible reex ICP elevation.
Propofol may be the ideal sedative to use in
patients with elevated ICP; besides the fact that it is

63

ultrashort acting, it has favorable effects on ICP and

seizure activity, and may have neuroprotective
properties. In a study comparing propofol to
morphine in patients with severe TBI, patients
treated with propofol had lower ICP values and
more favorable long-term neurologic outcomes
[64]. By contrast, paralysis with neuromuscular
blocking agents such as vecuronium, pancuronium,
or cis-atracurium is rarely necessary, and places
patients at risk for prolonged paralysis due to
critical illness myopathy.
STEP 3: CPP OPTIMIZATION. If CPP is less than 70
mmHg and ICP is greater than 20 mmHg, elevation
of mean arterial blood pressure and CPP with a
vasopressor such as dopamine or phenylephrine
(Table 8) can lead to a reex reduction of ICP, by
eliminating cerebral vasodilation that occurs in
response to inadequate perfusion (Fig 8). CPP
optimization to levels well above 70 mmHg may
be desirable in chronically hypertensive patients
(whose autoregulatory curve is shifted to the right),
or in patients with low PbtO2 or SjvO2 levels or
Lundberg A and B waves (since these ndings
generally reect insufcient CPP). The widely
accepted ``one size ts all'' approach to CPP
management (>70 mmHg) is in all likelihood an
oversimplication, and efforts should be made to
optimize CPP whenever patients fail standard
therapy. One study that attempted to dene optimal
CPP levels for severe TBI patients by analyzing
receiver-operating curves found that a CPP of 55
mmHg was the critical threshold for poor outcome
in adults [65]. It seems prudent to maintain CPP well
above this level in clinical practice, however, to
provide an extra margin of safety. In an uncontrolled study of TBI patients with CPP maintained above 70 mmHg with phenylephrine and

Table 7. Selected Short-Acting Intravenous Sedatives for ICP Management

Agent

Pharmacology

Dosage Range

Morphine sulfate

Opioid (sedative-hypnotic with analgesic

properties)

25 mg IVP every 14 hours

Fentanyl

Opioid (short acting, 100 times more potent than

morphine)

0.53.0 lg/kg/hr

Sufentanil

Opioid (ultrashort acting)

0.10.6 lg/kg/hr

Propofol

Alkylphenol (ultrashort acting)

0.66 mg/kg/hr

Midazolam

Benzodiazepine (short acting)

0.050.1 mg/kg/hr

Sedative-analgesic agents

Sedative-hypnotic agents

Dosages are approximate and should be titrated to the patient's level of agitation and ICP. A combination of a sedative-analgesic and
sedative-hypnotic agent may be more effective than the use of a single agent.

64

Journal of Intensive Care Medicine Vol 17 No 2 March/April 2002

Table 8. Selected Short-Acting Vasoactive Drugs for ICP

Management
Agent

Pharmacology

Dosage Range

Blood pressure reduction

Labetolol

a1 and b1 blocker 23 mg/min

Nicardipine

Calcium channel 515 mg/hr

blocker

Blood pressure elevation

Dopamine

a1 and b1 agonist 530 lg/kg/min

(at high doses)

Norepinephrine a1 and b1 agonist 0.030.6 lg/kg/min

Phenylephrine a1 agonist

210 lg/kg/min

norepinephrine, better outcomes were obtained

than in previously reported patients with strictly
ICP-based management [41].
If MAP and ICP are elevated in a sedated patient,
treatment of arterial hypertension can sometimes
lead to a parallel reduction of ICP. If CPP is greater
than 110 mmHg and ICP is greater than 20 mmHg,
hypertension should be carefully treated with a
short-acting agent (Table 7). However, extreme
caution should be used to avoid reduction of CPP
below 70 mmHg, which can trigger reex cerebral
vasodilation and ICP elevation. Nitroprusside can
be particularly troublesome in this regard, and

Fig 8. Demonstration of CPP augmentation resulting in

reex ICP reduction. At approximately 9:30, the patient
developed a plateau wave with ICP elevation from 20 to
40 mmHg, and CPP reduction from 100 to 70 mmHg. A
dopamine infusion was started at 9:45, with nearly immediate normalization of ICP to 20 mmHg when CPP was
restored to 100 mmHg.

concerns also exist regarding the potential for

nitroprusside to directly dilate the cerebral vasculature and increase ICP. For these reasons, nitroprusside is best avoided in patients with elevated
ICP, and should only be used if an ICP monitor is in
place. Experimental and clinical studies have demonstrated that treatment of hypertension in patients
with intracerebral hemorrhage does not exacerbate
perilesional ischemia [66] or cause reex vasodilation and increased ICP [67], as long as CPP remains
within the normal range.
STEP 4: OSMOTHERAPY. If CPP is optimized, the patient
is sedated, and ICP remains elevated, mannitol or
hypertonic saline should be given. Mannitol, an
osmotic diuretic, lowers ICP via its cerebral dehydrating effects. The effects of mannitol are biphasic.
Rapid infusion immediately creates an osmotic
gradient across the blood-brain barrier, which leads
to movement of water from brain parenchyma
to the intravascular compartment. The result is
decreased brain tissue volume, and hence reduced
ICP [68]. The secondary effect of mannitol results
from its action as an osmotic diuretic. As mannitol is
cleared by the kidneys, it leads to free water
clearance and increased serum osmolality. This
leads to a more prolonged intracellular dehydrating
effect as water ows down the osmotic gradient
from the intracellular to the extracellular space.
The initial dose of mannitol 20% solution is 11.5
g/kg, followed every 16 hours with doses of 0.251
g/kg as needed. Repeated mannitol doses should
be given on the basis of ICP measurements rather
than as scheduled doses, unless the goal is to
establish and maintain a hyperosmolar state (300
320 mOsm/L). The effect of a mannitol bolus on ICP
begins within 1020 minutes, reaches its peak
between 20 and 60 minutes, and lasts for 46 hours,
but this may vary widely between patients. Adverse
effects of mannitol therapy include exacerbation of
congestive heart failure (due to the initial intravascular volume expansion); volume contraction,
hypokalemia, and profound hyperosmolality (after
prolonged use); acute tubular necrosis (due to
excessive hyperosmolality); and ``rebound'' increases in ICP [69]. Patients treated repeatedly with
mannitol require frequent measurements of serum
electrolytes and osmolality, careful recording of
uid input and output, and central venous pressure
monitoring. Urinary volume losses should be
replaced with normal (0.9%) saline to avoid volume
depletion.
Bolus infusion of 3%, 7.5%, 10%, or 24.3%
hypertonic saline is gaining popularity as an
alternative to bolus infusions of mannitol for ICP
crises [43]. In an uncontrolled study of 3% saline/

Mayer and Chong: Management of ICP

acetate infusion (75150 ml/hr) and intermittent

boluses (250 ml) titrated to maintain serum sodium
levels between 145 and 155 mEq/L, hypertonic
saline lowered ICP related to TBI and brain tumors,
but not in patients with intracerebral hemorrhage or
cerebral infarction [70]. Infusion of 25 ml/kg of
7.5% saline or 0.51.0 ml/kg of 23.4% saline over 30
minutes has also been shown to lower elevated ICP
and augment CPP, with an effect that lasts several
hours [71,72]. A large head-to-head trial of mannitol
versus hypertonic saline is warranted.
STEP 5: HYPERVENTILATION. As a general rule, the goal
of hyperventilation for ICP control should be to
lower pCO2 to 30 mmHg, or to 2530 mmHg in
extreme cases. The respiratory alkalosis caused by
hyperventilation lowers ICP by causing cerebral
vasoconstriction and reduced CBV [1]. The peak
effect of hyperventilation on ICP is generally
reached within 30 minutes. Over the next 13 hours
the effect gradually diminishes, as compensatory
acid-base buffering mechanisms correct the alkalosis within the central nervous system [1]. In patients
with elevated ICP due to hyperemia and increased
CBV, however, the effect may be prolonged, and
hyperventilation may be the treatment of choice
[73]. Hyperventilation should be tapered slowly
over 46 hours because abrupt cessation may lead
to vasodilation and rebound increases in ICP.
Though it is postulated that prolonged severe
hyperventilation (pCO2 < 25 mmHg) can actually
exacerbate cerebral ischemia by causing profound
vasoconstriction, the deleterious effects of excessive hyperventilation may also include more labile
ICP. In a study of patients with TBI, prophylactic
hyperventilation to a pCO2 of 25 mmHg resulted in
poorer outcome compared with normally ventilated patients [74]. The authors hypothesized that
blood vessels may become hypersensitive to changes in pCO2 after prolonged hyperventilation
because CSF buffering capacity is lost. In cases of
pediatric head trauma, profound hypocarbia was
associated with decreased cerebral oxygen consumption and ischemia [75]. SjvO2 monitoring is a
useful modality for ensuring that prolonged
aggressive hyperventilation, if necessary, is not
critically reducing oxygen delivery to the brain.
STEP 6: PENTOBARBITAL THERAPY. High-dose barbiturate therapy, given in doses equivalent general
anesthesia, can effectively lower ICP in most
patients refractory to the steps outlined above
[76,77]. The effect of pentobarbital is multifactorial,
but most likely stems from a profound reduction of
cerebral metabolism, which is coupled to reductions of CBF and CBV [78]. Pentobarbital often

65

causes hypotension, and usually requires the use of

vasopressors to maintain CPP above 70 mmHg.
Pentobarbital typically requires a loading dose of
1020 mg/kg, given in repeated 5 mg/kg boluses,
until a state of accid coma with preserved pupillary
reactivity is attained. Maintenance infusion is usually about 14 mg/kg/hr. Continuous EEG monitoring is helpful to avoid oversedation, since generally no further ICP reduction occurs once a burstsuppression pattern is attained. If ICP is normalized
with pentobarbital, it is generally maintained for
2448 hours. It can then be abruptly discontinued
because its highly lipophilic nature and long halflife (90 hours) result in a gradual reduction of blood
levels over several days.
STEP 7: HYPOTHERMIA. Systemic hypothermia to levels of 3233C can lower ICP in some patients
refractory to pentobarbital [7981]. This technique
requires placement of cooling blankets under and
over the patient, iced gastric lavage, and pharmacologic paralysis with vecuronium or a similar
neuromuscular blocking agent to prevent shivering. Prolonged hypothermia can be dangerous
because of increased risk of infectious complications, coagulopathy, and electrolyte derangements,
among other hazards. Rewarming should always be
done slowly, over at least a day, and passively,
without active heating, to avoid rebound cerebral
edema or a systemic inammatory response syndrome, which can be fatal.
In a small randomized controlled trial of severe
TBI patients refractory to pentobarbital, mild-tomoderate hypothermia (34C) signicantly reduced
ICP, improved CPP, reduced CBF and cerebral
metabolic rate (CMRO2), and reduced arteriojugular venous oxygen differences [79]. Survival was
50% in hypothermia patients compared to 18% in
the control group (p < 0.05). Later studies by the
same group reported that hypothermia was most
effective for pentobarbital-refractory ICP elevations
between 20 and 40 mmHg [80], and that severe TBI
patients with low ICP do not benet from hypothermia [81]. These reports, and the negative results
of a recent large National Institutes of Health (NIH)funded trial studying the effects of hypothermia as
rst-line therapy for severe TBI [82], suggest that
hypothermia is not effective as a primary form of
neuroprotection for severe TBI related to diffuse
axonal injury.

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