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Management of Intracranial Pressure
Thomas J. Wolfe, MD, and Michel T. Torbey, MD, MPH
Corresponding author
Thomas J. Wolfe, MD
Department of Neurology, Medical College of Wisconsin
and Froedtert Hospital, 9200 West Wisconsin Avenue,
Milwaukee, WI 53226, USA.
E-mail: [email protected]
Current Neurology and Neuroscience Reports 2009, 9:477–485
Current Medicine Group LLC ISSN 1528-4042
Copyright © 2009 by Current Medicine Group LLC
Although intracranial hypertension may arise from
diverse pathology, several basic principles remain
paramount to understanding its dynamics; however,
the management of elevated intracranial pressure
(ICP) may be very complex. Initial management
of common ICP exacerbants is important, such as
addressing venous outflow obstruction with upright
midline head positioning and treating agitation and
pain with sedation and analgesia. Surgical decompression of mass effect may rapidly improve ICP
elevation, but the impact on outcome is unclear.
Considerable effort has been put forth to understand
the roles of multimodal intensive care monitoring,
osmolar therapy, cerebral metabolic suppression, and
temperature augmentation in the advanced management of elevated ICP. Establishing a protocol-driven
approach to the management of ICP enables the rapid
bedside assessment of multiple physiologic variables
to implement appropriate treatments, which limit the
risk of developing secondary brain injury.
Introduction
Numerous neurologic and nonneurologic diseases may
contribute to the formation of intracranial hypertension.
Through advances in emergency response systems and
neuroimaging, the rapid identification of these patients
has become easier, allowing for earlier initiation of treatment. Recent technical innovations in neuromonitoring
and the establishment of specialized neurointensive care
units may allow for improvements in morbidity and mortality rates attributable to elevated intracranial pressure
(ICP). We present a review of ICP physiology and data to
support the evidence-based management of these patients.
In addition, we present a possible treatment algorithm for
refractory intracranial hypertension, incorporating the
application of multimodal monitoring in the neurointensive care unit.
ICP Dynamics
The cranial vault of a normal adult is a noncompliant
structure containing an average volume of approximately
1500 mL, comprising 88% brain matter, 7.5% blood, and
4.5% cerebrospinal fluid (CSF) [1]. The Monroe-Kellie
hypothesis contends that to maintain a constant ICP, any
increase in the volume of an intracranial element must be
met with an equal compensatory decrease in the volume
of another component, or pressure will increase. Because
of the skull’s noncompliance, uncompensated changes in
the volume of any given component may have an impact
on ICP, with a potential exponential increase in ICP.
Normal ICP is not constant throughout life; healthy
adults and older children have a normal ICP of 10 to 15
mm Hg, whereas the ICP of young children and infants is
more than half this value [2,3]. There is level II evidence
to support treatment initiation if ICP levels remain persistently above 20 mm Hg [4]. For the purposes of this
review and the proposed treatment algorithm (Fig. 1),
sustained ICP elevation greater than 20 mm Hg without
stimulation fulfi lls the criteria for intervention.
Cerebral blood flow and perfusion pressure
The brain receives 15% to 20% of total cardiac output,
which at rest is approximately 800 mL/min, and absorbs
25% of all oxygen consumed by the body [5]. Systemic
mean arterial perfusion pressure (MAP) is the most
important factor in maintaining cerebral perfusion. Cerebral perfusion pressure (CPP), the pressure at which the
brain is perfused, is determined by taking the difference
between MAP and ICP (CPP = MAP – ICP), where MAP
= (1/3 systolic blood pressure [BP]) + (2/3 diastolic BP).
Normally, cerebral blood flow (CBF) is estimated to be 50
mL/100 g per minute. When CBF falls below 12 mL/100
g per minute, irreversible ischemic injury occurs [5].
Maintaining a constant CBF depends on autoregulation, a complex system of arterial and venous modulation.
Autoregulation has three main levels of control: myogenic,
metabolic, and neurogenic [5,6]. Pressure autoregulation
refers to the cerebrovascular system’s ability to maintain
normal levels of CBF with CPP between 50 and 150 mm
Hg, mediated mainly by the variable vascular resistance of
arteriolar myogenic responses. The metabolic regulation of
arteriolar vascular resistance is variably affected by CO2,
O2, pH/lactate formation, adenosine, and nitric oxide. Neurogenic regulation refers to sympathetic tone on the cerebral
arteries leading to mild tonic vasoconstriction, allowing for
higher limits on the autoregulation curve; in contrast, the
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Figure 1. Medical College of Wisconsin algorithm for the management of increased intracranial pressure (ICP). Multimodal monitoring and
second-tier therapies can be introduced for refractory elevations in ICP. CPP—cerebral perfusion pressure; EAC—external auditory canal;
Hct—hematocrit; MAP—mean arterial pressure; PtO2—parenchymal oxygen partial pressure; SjO2—jugular bulb venous oxygen saturation.
parasympathetic nervous system plays little role in cerebral
autoregulation [5]. Measuring the limits of cerebral vascular
autoregulation is possible using transcranial Doppler technology by comparing beat-to-beat spontaneous variability in
systemic BP with CBF velocities [6].
If CPP levels fall below the lower limit of autoregulation, CBF will fall and contribute to oligemia. If CPP
exceeds the upper limit of autoregulation, an excess of
CBF would occur beyond the metabolic necessity of the
brain. This is an uncoupled increase in CBF, or luxury
perfusion. Recent animal data suggest that the lower limit
of cerebral autoregulation rises as ICP increases, which
might mandate a progressively higher CPP goal to maintain constant CBF [7].
Causes of elevated ICP
Acute identification and treatment of the primary cause of
elevated ICP are necessary to reduce the risk of developing
further secondary injury, and other, secondary causes of
ICP elevation also must be addressed [8]. Common causes
of ICP elevation are outlined in Table 1.
Patterns of ICP elevation
The natural history of intracranial hypertension depends
on the underlying pathogenesis. In traumatic brain injury
with a mass lesion, elevations in ICP may present acutely,
prompting urgent surgical intervention. In a prospective
evaluation of the time course of intracranial hypertension
following traumatic brain injury (TBI), half the patients
had their highest ICP within 3 days of the injury, whereas
25% had the highest mean ICP after 5 days [9]. The
patients who experienced the later peak in ICP tended to
have a poorer clinical grade and were more refractory to
treatment. O’Phelan et al. [10] also described a significant number of patients who experienced late peak rises
in ICP, and identified four patterns of ICP elevation following severe TBI: increases beginning within 72 hours
(early); increases beginning after 72 hours (late); early
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Table 1. Causes of elevated intracranial pressure
Primary intracranial pathology
Primary extracranial pathology
Traumatic injury (contusion, diffuse axonal injury)
Hypoxia
Intracranial hemorrhages (epidural, subdural,
subarachnoid, parenchymal, tumoral)
Hypercarbia
Ischemic infarction with cytotoxic edema
Hypertension
Neoplasm and associated vasogenic edema
Hyponatremia
Hydrocephalus
Jugular venous obstruction
Infection (meningitis, encephalitis, abscess,
neurocysticercosis, malaria)
Agitation and valsalva
Status epilepticus
Mechanical ventilation (when peak end expiratory
pressure > baseline intracranial pressure)
Postoperative: hemorrhage, retraction, edema,
or cerebrospinal fluid obstruction
Hyperpyrexia
Convulsive seizure or depolarizing paralytic
Hepatic failure
High-altitude cerebral edema
Toxins and medications (lead, tetracycline,
doxycycline, rofecoxib, retinoic acid)
increases with resolution, followed by a second rise after
72 hours (bimodal); and continuously increased ICP.
Disease processes that develop delayed edema formation
(eg, ischemic stroke, hematomas) may require extended
monitoring periods, with cranial imaging to guide the discontinuation of monitoring. Prolonged ventriculostomy
use or permanent CSF shunt placement may be required
for hydrocephalus following subarachnoid hemorrhage or
mass effect onto the normal CSF-draining pathway.
ICP Monitoring
Indications for ICP monitoring
Headache, nausea and vomiting, somnolence, and
pupillary dilatation are signs of elevated ICP. Although
papilledema is a specific indicator of intracranial hypertension, it may be present only in a minority of patients
[8]. Imaging guidance (midline shift, effaced basal cisterns) also may assist in the identification of patients with
a suspected increase in ICP, but significant ICP elevations
may occur without these fi ndings.
The Brain Trauma Foundation has formulated guidelines for the use of ICP monitors, helping standardize the
approach to their placement [11]. Level II evidence exists
to support monitoring in all salvageable patients with a
severe TBI (Glasgow Coma Scale score of 3–8 after resuscitation) and an abnormal CT scan. An abnormal CT
scan of the head is defi ned as one that reveals hematomas,
contusions, swelling, herniation, or compressed basal cisterns. Level III evidence supports monitoring in patients
with severe TBI who have a normal CT scan, if two or
more of the following features are noted at admission: age
over 40 years, unilateral or bilateral motor posturing, or
systolic BP less than 90 mm Hg. Some variability exists
in patient selection for the placement of an ICP monitor
because of the lack of prospective randomized trials sup-
porting their role. Shafi et al. [12•] reported a retrospective
analysis of the National Trauma Data Bank suggesting
a 45% reduction in survival when ICP monitoring was
performed according to guidelines similar to those stated
previously; only 43% of patients meeting guideline criteria
underwent ICP monitoring. The significance of this fi nding is unclear and may represent morbidity related to the
treatment prompted by monitoring, or may suggest that
the patient’s severity of injury was overestimated at the
time of monitor placement.
Guidelines for the use of ICP monitoring for pathology
other than trauma are less clearly established. However,
adopting inclusion criteria similar to those used for TBI
may help guide appropriate application in patients with
nontraumatic intracranial hypertension. Clinical deterioration and imaging consistent with mass effect may serve
as important selection criteria.
ICP monitors and waveforms
Various intracranial monitoring devices exist, with the
ventricular drain being the gold standard [8]. Ventricular
catheters can be zeroed repetitively, whereas parenchymal or subarachnoid bolt strain monitors are subject to
delayed drift and cannot be re-zeroed after placement.
Ventricular catheters also offer a therapeutic function,
allowing CSF volume reduction.
Normal ICP waveforms are similar to the arterial
waveform, with a fi rst peak correlating with systole, a
second peak correlating with aortic valve closure, and a
third peak correlating with antegrade arterial flow during
diastole; with reduced brain compliance, the second peak
may be higher than the fi rst. Self-perpetuating ICP elevations (plateau waves) may occur when reductions in CBF
lead to vasodilation and subsequent increases in ICP that
in turn impair CBF, ultimately leading to further vasodilation and increases in ICP.
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Initial Clinical Management of ICP
The initial management of patients suspected of having
elevated ICP should include resuscitation to ensure airway
protection, normal oxygenation monitored with pulse
oximetry and arterial blood gases (O2 saturation > 90%
or Pao2 > 60 mm Hg), and systolic BP greater than 90
mm Hg. Insurance of euvolemia and strict monitoring of
in/out balance with a Foley catheter are necessary. Head
of bed should be maintained at 30°, and the patient’s head
should remain in midline positioning, without jugular
compression, to promote venous return. For patients with
loss of consciousness and cranial imaging abnormalities,
prophylactic antiepileptic medication should be considered to limit the possibility of seizure-related ischemia
and hypertension. Sedation should be initiated (allowing
for clinical assessments) and paralysis considered; the use
of non-depolarizing paralytics is preferred to avoid ICP
elevations associated with muscular contraction. Hyperventilation should be used only acutely to achieve Pco2
of approximately 33 mm Hg; prolonged hyperventilation should be avoided because of the sustained changes
in autoregulation that may occur, and extensive acute
reduction in Pco2 may cause vasoconstriction, contributing to cerebral ischemia. The initial CPP goal should be
maintained at greater than 60 mm Hg; values less than
60 mm Hg may be associated with worsened mortality
[13], although CPP greater than 70 mm Hg has not been
shown to improve outcome [14].
Surgical Intervention
Surgical decompression of an intracranial space-occupying lesion remains an acute intervention that can have an
immediate impact on ICP elevations that are refractory
to medical therapies, often with a durable effect. Decompressive craniectomy has been evaluated as the primary
surgical intervention for hemorrhagic contusion following
TBI, illustrating safety and efficacy, with reductions in
both mortality and the need for additional surgery [15].
Although patients undergoing craniectomy had somewhat
improved outcomes compared with those undergoing
craniotomy with focal lesion evacuation, there was no
difference in hospital or rehabilitation length of stay. A
40% rate of improved outcome in patients undergoing
craniectomy for severe TBI has been seen, with older age
as a potential exclusionary criterion [16]. The impact of
decompressive craniectomy on cerebral oxygenation,
vascular reactivity, and neurochemistry following severe
TBI was assessed, suggesting that in patients who had
good functional outcomes, these physiologic parameters
normalized [17]. These fi ndings may offer insight into
factors that can help aid in prognostication. The HAMLET (Hemicraniectomy After Middle Cerebral Artery
Infarction With Life-Threatening Edema) trial specifically
enrolled patients with middle cerebral artery infarction
and life-threatening mass effect from edema prospectively
at multiple centers [18]. This trial in 64 patients found an
absolute risk reduction in mortality of 38%. In addition,
poor outcomes may be reduced if the procedure is performed within 48 hours of stroke onset, a benefit that may
not persist if delayed up to 96 hours; this benefit on functional outcome has not been validated. The RESCUEicp
(Randomised Evaluation of Surgery With Craniectomy for
Uncontrollable Elevation of Intra-Cranial Pressure) trial is
an international multicenter prospective randomized trial
that will assess the efficacy of craniectomy in the management of ICP elevation attributable to many different causes
[19••]. As of April 2009, one third of an anticipated 600
patients were enrolled. Once completed, this study should
help defi ne the role of craniectomy in ICP management.
Although surgery may have an acute impact on ICP, its
use in the management of ICP should be considered on an
individual basis, as the effect on meaningful outcome has
not been fully proven for all patients.
Second-Tier Medical Management of ICP
When ICP elevations remain refractory to initial medical
therapy and the patient does not meet surgical criteria,
or if the pressure remains elevated following surgery,
more intensive measures must be implemented. No large
prospectively validated randomized trials have been performed to evaluate the use of multimodal monitoring on
outcome, or the relative efficacy of one intervention over
the others. Despite this limitation, the application of these
interventions and newer technology allow for improving
goal-directed care. Forming an evidence-based treatment
algorithm enables the rapid interpretation of multiple
physiologic parameters. Figure 1 is an example of the protocol employed at our institution. Some potential adverse
effects encountered during ICP management are outlined
in Table 2.
Multimodal monitoring
Multimodal neuromonitoring may allow insight into the
deranged cerebral metabolic balance that occurs following a brain injury or stroke. Although the measurement
of ICP and evaluation of CPP remain the foundation
of current intracranial hypertension management, the
adjunctive use of more complex monitoring methodology
may help limit secondary injury.
CBF is closely linked to the metabolism of oxygen,
and the arteriovenous difference in oxygen content
(AVTO2) can be measured to evaluate the adequacy of
cerebral perfusion. The monitoring of a jugular bulb
venous oximetry (SjO2) can be achieved with bedside
catheter placement and provides a continuous estimate
of cerebral venous oxygen saturation; suggested normal
values for SjO2 range from 50% to 65% [20]. In Figure
1, strict SjO2 targets are set higher to reduce the chances
of hypoxemia. If frequent or sustained hyperventilation
is utilized, SjO2 monitoring may help prevent vasoconstriction-related ischemia. Similarly, when cerebral
perfusion is inadequate or below the lower threshold for
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Table 2. Some potential adverse effects associated with intracranial pressure treatments
Treatment
Adverse effects
Seizure prophylaxis
Encephalopathy
Sedation
Neuromuscular blockade/chemical paralysis
Loss of clinical examination
Myopathy
Prolonged paralysis
Raised intracranial pressure
(with muscular contraction from depolarizing blockers)
Hyperventilation
Vasoconstriction-related ischemia
Chronic changes in autoregulation
Intracranial pressure monitoring
Intracranial hemorrhage (epidural, subdural, parenchymal, ventricular)
Infection
Pain at insertion site
Mannitol/osmotic diuretics
Congestive heart failure
Volume depletion
Pulmonary and peripheral edema
Electrolyte abnormalities (pseudo-hyponatremia)
Osmotic nephropathy (especially when volume depleted)
Hypertonic saline
Congestive heart failure
Hypotension (during bolus)
Pulmonary and peripheral edema
Hyperchloremic metabolic acidosis
Osmotic myelinolysis
Rebound edema on discontinuation
Pharmacologic metabolic suppression
Barbiturates
Sedation/loss of clinical examination
Respiratory depression and hypercarbia
Hypotension and cardiac suppression
Infection
Propofol
Similar to barbiturates
Propofol infusion syndrome
Acute refractory bradycardia leading to asystole,
with one or more of the following:
Metabolic acidosis
Rhabdomyolysis
Hyperlipidemia (triglycerides)
Enlarged or fatty liver
Therapeutic hypothermia
Electrolyte abnormalities (hypokalemia, hypocalcemia)
Cardiac suppression, both atrial and ventricular arrhythmias
(including asymptomatic electrocardiographic changes)
Infection due to immune suppression
Reduced creatinine clearance (during the active phase of hypothermia)
Pancreatitis
autoregulation, low levels of SjO2 and high AVTO2 might
represent excessive O2 extraction. With pressure-passive
elevations of ICP, when the upper limit of autoregulation
is exceeded or autoregulation is lost, high values of SjO2
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and low AVTO2 may be seen because of an uncoupled
increase in luxury perfusion.
The exact significance of parenchymal oxygen tension
(PbO2) is unclear, but its application in ICP management
is important. It has been seen that SjO2 of approximately
50% correlates with PbO2 of approximately 8.5 mm Hg
(range, 3–12 mm Hg); PbO2 is possibly a more durable
method for longer monitoring [21]. In a small cohort of
TBI patients, it was determined that measurements of
PbO2 more accurately represented CBF and the cerebral
AVTO2 than direct measurement of total cerebral oxygen
delivery or oxygen metabolism [22]. If this relationship is
validated, these fi ndings may preempt the need for SjO2
or AVTO2 monitoring while PbO2 is being assessed, especially in patients with cervical spine injury or cerebral
venous occlusion. In a larger prospective trial implementing treatment thresholds of PbO2 greater than 20 mm
Hg and ICP greater than 20 mm Hg, reduced mortality
rates were seen using an ICP/PbO2-directed protocol [23].
Improved 6-month outcomes over standard ICP/CPP
therapy also were seen. The assessment of autoregulation
also may be possible through oxygen pressure reactivity assessment, which correlates with cerebrovascular
pressure reactivity [24]. These detailed evaluations may
be appropriate mostly for patients with refractory ICP
despite escalating therapies and require additional data
processing hardware.
Electrophysiologic monitoring in the neurointensive
care unit is common. Recently, the concept of detecting
neurologic deterioration using electroencephalography
and somatosensory evoked potentials was defi ned [25].
Of the patients in this study who had elevations in ICP,
68% had worsening of evoked responses either before
or during the worsened ICP. Interpretation of these
bedside data could allow earlier thresholds for initiating an additional level of therapy. Intraparenchymal
electrographic recording has been introduced as an
addition to the multimetric bolt monitors. This technology may allow for detection of seizure activity surface
electroencephalography cannot discern because of the
underlying brain injury.
Cerebral microdialysis is another method that is being
refi ned for the evaluation of metabolism and biochemistry.
Microdialysis catheters are placed within the parenchyma,
and with the use of variably sized semipermeable membranes, molecules are collected and evaluated. Markers
of glucose metabolism (lactate, pyruvate), excitotoxicity
(glutamate), and membrane breakdown (glycerol) are most
commonly evaluated using microdialysis [26•]. Although
monitoring of microdiasylate glucose and lactate concentrations might help with tailoring glycemic control, the
exact role of this evaluation in the routine management of
ICP is not clear at this time.
Osmolar therapy
The blood–brain barrier (BBB) is relatively impermeable to
most low molecular weight solutes present in blood (pre-
dominantly sodium and chloride), as well as to the plasma
proteins. The permeability of an osmotic agent across a
semipermeable membrane such as the BBB is quantified
by a reflection coefficient, where values approaching 0
represent high permeability and those approaching 1 have
low permeability [27]. Therefore, an increase in plasma
osmolality always leads to decreases in brain parenchymal
fluid volume. The most frequently used osmoles today are
mannitol and sodium (reflection coefficient ~ 0.9 and 1,
respectively). Other osmolar solutes, such as glycerol, sorbitol, and urea, have lower reflection coefficients and may
lead to increases in parenchymal total fluid volume after
diffusing into the brain and exerting osmotic pressure.
Analysis of perfusion imaging may allow insight into the
integrity of the BBB following brain injury [28], possibly
offering a marker for limitations on osmolar therapy use.
Additional effects may be imparted by mannitol and
hypertonic saline. Mannitol has been found to upregulate subsets of cerebral aquaporin receptors, which may
facilitate the redistribution of water between normal and
abnormal regions of the brain [29]. Hypertonic saline may
also contribute to increases in CBF [30].
The rate of administration of an osmolar load may
affect the efficacy of lowering ICP. Sustained administration and lower weight-based dosing of mannitol have been
shown to have a less pronounced and less enduring impact
on elevated ICP [31•]. Bolus dosing may create a higher
osmolar gradient across the BBB, ultimately inducing a
larger decrease in parenchymal fluid. When the efficacy
of mannitol was compared with that of hypertonic saline,
there was a significant decrease in ICP from hypertonic
saline compared with mannitol, along with significant
increases in MAP and CPP; improvements in cerebral oxygenation also have been seen with hypertonic saline [32].
This difference may be explained by the diuretic effect
of mannitol, causing reductions in intravascular volume.
Following initial dosing of mannitol during resuscitation,
the adjunctive use of hypertonic saline should be considered for persistent ICP elevations.
In refractory cases, mannitol and hypertonic sodium
may be alternated or given simultaneously. Monitoring the
serum osmolar gap is helpful for monitoring the extent of
mannitol administration and estimating serum concentration. After initiating osmolar therapy with mannitol, the
measured serum osmolality goal traditionally has been 320
mOsm/L. However, with the use of hypertonic sodium
solutions for elevated ICP occurring more commonly, standardized osmolality goals may become obsolete. A more
rational approach may be the osmolar gap calculation—gap
= measured – calculated osmolality; calculated osmolality
= (2Na) + (glucose/18) + (blood urea nitrogen/2.8)—to
estimate serum levels and guide the administration of
mannitol [33]. Gap values less than 10 would suggest it
is safe for administration of additional mannitol, with an
increased risk of adverse effects if gap persists at greater
than 20. If hyperchloremic metabolic acidosis develops
with hypertonic saline administration, hypertonic sodium
Management of Intracranial Pressure
bicarbonate solutions may serve as an effective alternative
[34]; partial or complete substitution of chloride for acetate
(bicarbonate equivalent) is another alternative.
Metabolic suppression
Metabolic suppression may be used to treat elevations in ICP,
assuming tissue viability and coupling of blood flow to the
metabolic demand of the brain. By inducing a reduced metabolic requirement, the amount of blood flow required by the
brain also is reduced. Additional excitotoxic processes also
may be attenuated. Here, more emphasis has been placed
on therapeutic hypothermia, which is an emerging therapy
compared with pharmacologic suppression.
Pharmacologic suppression
Barbiturate therapy to induce electroencephalographic
burst suppression has been a mainstay of pharmacologic
metabolic suppression for elevated ICP, although it is not
indicated for prophylactic administration [35]. Signifi cant morbidity may be associated with this therapy and
should be reserved for cases of ICP refractory to standard
fi rst-line medical care, and hemodynamic stability is
mandatory before and after induction. Traditionally, an
electroencephalogram has been used to monitor neural
activity, although this may be assessed using bispectral
index monitoring to allow for easier evaluation [36],
especially in non–neurointensive care units. Barbiturate
coma may lower ICP and improve cerebral oxygenation
[37]. This improvement in cerebral oxygenation has been
partly validated in additional reports, although in areas
of impaired cerebral physiology, worsening oxygenation
may be seen [38]. The worsening may reflect difficulties
maintaining adequate CPP in regions of the brain with
impaired autoregulation.
Propofol, along with other sedative/hypnotics, has
been used to induce sedation and coma in place of barbiturates, demonstrating safety and efficacy [35,39].
In addition to neural suppression caused by activation
of the J-aminobutyric acid A receptor and inhibition of
the N-methyl-d-aspartate receptor, propofol may have a
direct neuroprotective effect [40]. The beneficial effects of
propofol may be countered by cardiovascular suppression
affecting CPP, leading to reduced cerebral flow in areas
with impaired autoregulation.
Therapeutic hypothermia and temperature augmentation
Fever is common following brain injury, and avoidance
of hyperthermia may be an important part of the management of brain injury from any cause [41•,42,43].
Intracranial temperature has been shown to be higher
than core body temperature [42], representing an important treatment consideration because of the relationship
between elevations in ICP and intracranial temperature.
Fever reduction in acute brain injury also may significantly
reduce systemic metabolic demand, although this may
depend on control of shivering [43]. The adverse effects
of temperature elevations above 37°C may be mediated by
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multiple pathogenic mechanisms, including excitotoxicity, free radical generation, inflammation, apoptosis, and
genetic differences in response to injury [44].
The application of mild therapeutic hypothermia, maintaining core body temperature near 33°C, is a novel strategy
used to provide neuroprotection following brain injury in
many clinical scenarios presenting with coma [41•]. Several
modalities are available for the induction of hypothermia:
external cooling devices, intravenous cold saline infusion,
and intravascular cooling catheters. Each of these methods
is associated with individual risks and benefits.
There may be a treatment window for hypothermia
induction to impart measurable clinical benefit, with a
possible lack of benefit seen in instances of delayed application for TBI [45]. The rate of rewarming is another
important aspect in treatment efficacy, with elevations
beyond normothermia potentially imparting deleterious
effects because of impaired cerebrovascular regulation
[41•,46•,47].
Although initial reports supported the role of hypothermia induced within 6 hours of TBI, subsequent
studies failed to show a benefit on neurologic recovery [48].
Patients with ICP elevations refractory to standard osmolar
therapy may benefit from hypothermia, but any benefit over
medication-induced metabolic suppression is unclear [49].
It is possible that if a patient fails to improve with pharmacologic metabolic suppression, there may not be any
further improvement following induction of hypothermia,
although it may act synergistically when a response is seen.
If hypothermia is applied in the setting of refractory elevations in ICP, further reduction in temperature beyond 32°C
has not been shown to impart further efficacy, and more
complications may be encountered [50]. However, if recurrent elevations in ICP are encountered during rewarming,
slowing the rate of rewarming or extending the duration of
hypothermia may be necessary. This may pose a problem
with regard to accurately assessing neurologic prognosis in
a timely manner, because sedatives and paralytics often are
required during hypothermia.
Conclusions
Recent advances in technology have allowed significant
improvement in the management of intracranial hypertension. Using bedside physiologic data, including ICP
transduction and waveform analysis and monitoring of
SjO2 , PbO2 , and cerebral temperature, optimization of cerebral perfusion and oxygenation and prevention of additional
secondary injury may be possible. Establishing protocols to
aid in the management of intracranial hypertension may
improve the quality of care through standardization of
treatment, based on real-time physiologic analysis.
Acknowledgment
Dr. Wolfe is the 2009–2010 Daniel M. Soref Clinical
Neurosciences fellow.
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Disclosure
No potential confl icts of interest relevant to this article
were reported.
References and Recommended Reading
Papers of particular interest, published recently,
have been highlighted as:
•
Of importance
••
Of major importance
Dóczi T: Volume regulation of the brain tissue—a survey.
Acta Neurochir (Wien) 1993, 121:1–8.
2.
Welch K: The intracranial pressure in infants. J Neurosurg
1980, 52:693–699.
3.
Downard C, Hulka F, Mullins RJ, et al.: Relationship of
cerebral perfusion pressure and survival in pediatric braininjured patients. J Trauma 2000, 49:654–658.
4.
Bratton SL, Chestnut RM, Ghajar J, et al.: Intracranial
pressure thresholds. J Neurotrauma 2007, 24(Suppl
1):55–58.
5.
Franco Folino A: Cerebral autoregulation and syncope.
Prog Cardiovasc Dis 2007, 50:49–80.
6.
van Beek AH, Claassen JA, Rikkert MG, Jansen RW:
Cerebral autoregulation: an overview of current concepts
and methodology with special focus on the elderly. J Cereb
Blood Flow Metab 2008, 28:1071–1085.
7.
Brady KM, Lee JK, Kibler KK, et al.: The lower limit
of cerebral blood flow autoregulation is increased with
elevated intracranial pressure. Anesth Analg 2009,
108:1278–1283.
8.
Rangel-Castilla L, Gopinath S, Robertson CS: Management of intracranial hypertension. Neurol Clin 2008,
26:521–541.
9.
Stocchetti N, Colombo A, Ortolano F, et al.: Time course
of intracranial hypertension after traumatic brain injury. J
Neurotrauma 2007, 24:1339–1346.
10.
O’Phelan KH, Park D, Efi rd JT, et al.: Patterns of increased
intracranial pressure after severe traumatic brain injury.
Neurocrit Care 2009, 10:280–286.
11.
Bratton SL, Chestnut RM, Ghajar J, et al.: Indications for
intracranial pressure monitoring. J Neurotrauma 2007,
24(Suppl 1):37–44.
12.• Shafi S, Diaz-Arrastia R, Madden C, Gentilello L: Intracranial pressure monitoring in brain-injured patients is
associated with worsening of survival. J Trauma 2008,
64:335–340.
The authors present controversial fi ndings suggesting that placement of intracranial monitoring devices based on criteria similar
to current TBI guidelines may be associated with worsened clinical
outcome. Although the validity is not clear, it reemphasizes the
importance of considering patients individually for treatment,
rather than strictly following a protocol.
13.
Juul N, Morris GF, Marshall SB, et al.: Intracranial
hypertension and cerebral perfusion pressure: influence
on neurological deterioration and outcome in severe head
injury. The Executive Committee of the International
Selfotel Trial. J Neurosurg 2000, 92:1–6.
14.
Bratton SL, Chestnut RM, Ghajar J, et al.: Cerebral perfusion thresholds. J Neurotrauma 2007, 24(Suppl 1):59–64.
15.
Huang AP, Tu YK, Tsai YH, et al.: Decompressive craniectomy as the primary surgical intervention for hemorrhagic
contusion. J Neurotrauma 2008, 25:1347–1354.
16.
Morgalla MH, Will BE, Roser F, Tatagiba M: Do longterm results justify decompressive craniectomy after severe
traumatic brain injury? J Neurosurg 2008, 109:685–690.
17.
Ho CL, Wang CM, Lee KK, et al.: Cerebral oxygenation,
vascular reactivity, and neurochemistry following decompressive craniectomy for severe traumatic brain injury. J
Neurosurg 2008, 108:943–949.
1.
Hofmeijer J, Kappelle LJ, Algra A, et al.: Surgical decompression for space-occupying cerebral infarction (the
Hemicraniectomy After Middle Cerebral Artery infarction
with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol 2009, 8:303–304.
19.•• Hutchinson PJ, Corteen E, Czosnyka M, et al.: Decompressive craniectomy in traumatic brain injury: the randomized
multicenter RESCUEicp study (www.RESCUEicp.com).
Acta Neurochir Suppl 2006, 96:17–20.
This prospective randomized trial has not completed enrollment,
but when accrual is complete, it will serve as one of the highest
powered analyses of decompressive craniotomy for ICP elevation
developing from multiple etiologies. These data will generally
reflect global practice patterns, but subgroup analyses may further
yield varying efficacy for specific causes of elevated ICP.
20.
Robertson CS, Contant CF, Gokaslan ZL, et al.: Cerebral
blood flow, arteriovenous oxygen difference, and outcome
in head injured patients. J Neurol Neurosurg Psychiatry
1992, 55:594–603.
21.
Kiening KL, Unterberg AW, Bardt TF, et al.: Monitoring of
cerebral oxygenation in patients with severe head injuries:
brain tissue PO2 versus jugular vein oxygen saturation. J
Neurosurg 1996, 85:751–757.
22.
Rosenthal G, Hemphill JC, Sorani M, et al.: Brain tissue
oxygen tension is more indicative of oxygen diffusion than
oxygen delivery and metabolism in patients with traumatic
brain injury. Crit Care Med 2008, 36:1917–1924.
23.
Narotam PK, Morrison JF, Nathoo N: Brain tissue oxygen
monitoring in traumatic brain injury and major trauma:
outcome analysis of a brain tissue oxygen-directed therapy.
J Neurosurg 2009 May 22 (Epub ahead of print).
24.
Jaeger M, Schuhmann MU, Soehle M, Meixensberger J:
Continuous assessment of cerebrovascular autoregulation
after traumatic brain injury using brain tissue oxygen pressure reactivity. Crit Care Med 2006, 34:1850–1852.
25.
Amantini A, Fossi S, Grippo A, et al.: Continuous EEG-SEP
monitoring in severe brain injury. Neurophysiol Clin 2009,
39:85–93.
26.• Tisdall MM, Smith M: Cerebral microdialysis: research
technique or clinical tool. Br J Anaesth 2006, 97:18–25.
Microdialysis is an emerging technique that is currently very labor
intensive, making its widespread use difficult. Assuming its clinical
utility continues to be demonstrated, this technique may theoretically become bundled in a single multimodal monitoring device.
27.
Bhardwaj A: Osmotherapy in neurocritical care. Curr
Neurol Neurosci Rep 2007, 7:513–521.
28.
Dankbaar JW, Hom J, Schneider T, et al.: Dynamic perfusion CT assessment of the blood-brain barrier permeability:
fi rst pass versus delayed acquisition. AJNR Am J Neuroradiol 2008, 29:1671–1676.
29.
Arima H, Yamamoto N, Sobue K, et al.: Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a
p38 mitogen-activated protein kinase-dependent pathway in
rat astrocytes. J Biol Chem 2003, 278:44525–44534.
30.
Tseng MY, Al-Rawi PG, Pickard JD, et al.: Effect of
hypertonic saline on cerebral blood flow in poor-grade
patients with subarachnoid hemorrhage. Stroke 2003,
34:1389–1396.
31.• Keyrouz SG, Dhar R, Diringer MN: Variation in osmotic
response to sustained mannitol administration. Neurocrit
Care 2008, 9:204–209.
This article highlights the importance of rapidly establishing an
osmolar gradient to optimize the efficacy of treatment, rather than
just having an increase in serum osmolality occur.
32.
Oddo M, Levine JM, Frangos S, et al.: Effect of mannitol
and hypertonic saline on cerebral oxygenation in patients
with severe traumatic brain injury and refractory intracranial hypertension. J Neurol Neurosurg Psychiatry 2009,
80:916–920.
33.
García-Morales EJ, Cariappa R, Parvin CA, et al.: Osmole
gap in neurologic-neurosurgical intensive care unit: its
normal value, calculation, and relationship with mannitol
serum concentrations. Crit Care Med 2004, 32:986–991.
18.
Management of Intracranial Pressure
Smith R, Thomas M, Brown J: Raised intra-cranial pressure—sodium bicarbonate as an alternative hyperosmolar
treatment. J Neurosurg Anesthesiol 2008, 20:158.
35.
Bratton SL, Chestnut RM, Ghajar J, et al.: Guidelines
for the management of severe traumatic brain injury. XI.
Anesthetics, analgesics, and sedatives. J Neurotrauma 2007,
24(Suppl 1):S71–S76.
36.
Cottenceau V, Petit L, Masson F, et al.: The use of
bispectral index to monitor barbiturate coma in severely
brain-injured patients with refractory intracranial hypertension. Anesth Analg 2008, 107:1676–1682.
37.
Thorat JD, Wang EC, Lee KK, et al.: Barbiturate therapy
for patients with refractory intracranial hypertension
following severe traumatic brain injury: its effects on tissue
oxygenation, brain temperature and autoregulation. J Clin
Neurosci 2008, 15:143–148.
38.
Chen HI, Malhotra NR, Oddo M, et al.: Barbiturate infusion for intractable intracranial hypertension and its effect
on brain oxygenation. Neurosurgery 2008, 63:880–886.
39.
Kelly DF, Goodale DB, Williams J, et al.: Propofol in the
treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial. J Neurosurg
1999, 90:1042–1052.
40.
Kotani Y, Shimazawa M, Yoshimura S, et al.: The
experimental and clinical pharmacology of propofol, an
anesthetic agent with neuroprotective properties. CNS
Neurosci Ther 2008, 14:95–106.
41.• Polderman KH: Induced hypothermia and fever control for
prevention and treatment of neurological injuries. Lancet
2008, 371:1955–1969.
The author reviews multiple potential mechanisms for the efficacy
of temperature augmentation and therapeutic hypothermia in
neurologic diseases.
34.
I
Wolfe and Torbey
I
485
Rossi S, Zanier ER, Mauri I, et al.: Brain temperature,
body core temperature, and intracranial pressure in acute
cerebral damage. J Neurol Neurosurg Psychiatry 2001,
71:448–454.
43.
Hata JS, Shelsky CR, Hindman BJ, et al.: A prospective,
observational clinical trial of fever reduction to reduce
systemic oxygen consumption in the setting of acute brain
injury. Neurocrit Care 2008, 9:37–44.
44.
Dietrich WD, Bramlett HM: Hyperthermia and central
nervous system injury. Prog Brain Res 2007, 162:201–217.
45.
Markgraf CG, Clifton GL, Moody MR: Treatment window
for hypothermia in brain injury. J Neurosurg 2001,
95:979–983.
46.• Lavinio A, Timofeev I, Nortje J, et al.: Cerebrovascular
reactivity during hypothermia and rewarming. Br J Anaesth
2007, 99:237–244.
This publication offers insight into important aspects of successfully implementing and completing a hypothermia protocol, to
optimize the efficacy of the treatment.
47.
Soukup J, Zauner A, Doppenberg EM, et al.: The importance of brain temperature in patients after severe head
injury: relationship to intracranial pressure, cerebral
perfusion pressure, cerebral blood flow, and outcome. J
Neurotrauma 2002, 19:559–571.
48.
Clifton GL, Miller ER, Choi SC, et al.: Lack of effect of
induction of hypothermia after acute brain injury. N Engl J
Med 2001, 344:556–563.
49.
Polderman KH, Tjong Tjin Joe R, Peerdeman SM, et al.:
Effects of therapeutic hypothermia on intracranial pressure
and outcome in patients with severe head injury. Intensive
Care Med 2002, 28:1563–1573.
50.
Shiozaki T, Nakajima Y, Taneda M, et al.: Efficacy of moderate hypothermia in patients with severe head injury and
intracranial hypertension refractory to mild hypothermia. J
Neurosurg 2003, 99:47–51.
42.