management of traumatic brain injury in icu_2008

8/14/2019 Management of Traumatic Brain Injury in ICU_2008

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Management of Traumatic Brain Injury

in the Intensive Care Unit

Geoffrey S.F. Ling, MD, PhDa,b,*,Scott A. Marshall, MDa,b

aDepartment of Neurology, Uniformed Services University of the Health Sciences,

4301 Jones Bridge Road, Bethesda, MD 21042, USAbNeurosciences Critical Care, Johns Hopkins Hospital, 600 N. Wolfe Street,

Baltimore, MD, USA

Within the medical and scientific communities, traumatic brain injury

(TBI) has long been recognized as the leading cause of traumatic death

and disability. In the United States, a brain injury occurs every 7 seconds

and results in death every 5 minutes. This results in approximately 52,000patients dying from TBI each year and accounts for almost one third of

all trauma-related deaths. Most of these injuries are a direct result of falls,

motor vehicle accidents, and assaults. The cost for direct TBI medical care is

estimated at more than $56 billion per year [1,2]. The rising numbers of mil-

itary patients injured while serving in Operation Iraqi Freedom (OIF) and

Operation Enduring Freedom (OEF) in Afghanistan will increase these es-

timates. Most victims of civilian and military TBI are younger men [3,4].

The long-term burden of TBI in human and financial terms is staggering.

Currently, the number of TBI survivors is numbered in the millions and isgrowing. Many require extended rehabilitation. Because many of these pa-

tients are less than 40 years old when injured and are otherwise in good

physical health, they can live for decades, even if severely injured. The soci-

etal cost is large both in terms of direct care and lost productivity. A TBI

patient who was a potentially productive member of society now becomes

a consumer of services and chronic care resources. Further, this occurs in

the period of life when his or her contribution to society may be greatest

The opinions expressed in this work belong solely to those of the authors. They do not

and should not be interpreted as being representative or endorsed by the Uniformed Services

University, US Army, Department of Defense, or any other agency of the federal govern-

ment.

* Corresponding author.

E-mail address: [email protected] (G.S.F. Ling).

0733-8619/08/$ - see front matter. Published by Elsevier Inc.

doi:10.1016/j.ncl.2008.02.001 neurologic.theclinics.com

Neurol Clin 26 (2008) 409426
mailto:[email protected]://www.neurologic.theclinics.com/http://www.neurologic.theclinics.com/mailto:[email protected]


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[3]. Even minor injury can lead to significant disability. Up to 79% of mild-

moderate TBI patients had residual symptoms 3 months after injury. Many

were unable to return to their jobs. Considering that the estimated totalnumber of new TBI cases is greater than 1.4 million per year in the United

States, the problem of brain injury is more fully appreciated [4,5].

Over the past 20 years, there has been marked improvement in the overall

mortality associated with TBI. The reasons for this decrease in mortality

may be attributed to improved medical and surgical care. A retrospective re-

view compared a database of severely injured traumatic head injury patients

from the period 1984 to 1987 with a similarly matched group from 1988 to

1996. There was a decrease in overall mortality, which remained significant

despite adjustment for age, motor score, and pupillary reaction. The overallmortality from severe TBI in 1996 was reported as 27%, compared with

39% in 1984 [6]. The increasing role of specialized intensive care units

with neurologically trained medical and nursing providers using evidence-

based clinical management is believed to have had a favorable impact on

both the consistency and level of care. Advances in neuromonitoring, neuro-

imaging, and early aggressive neurosurgical interventions may also be im-

portant contributors to improved TBI outcome. Preventing and treating

comorbid conditions, such as venous thromboembolism, infection, and de-

cubitus ulcers, also likely had a positive role.Historically, 15% to 20% of injuries incurred in battle involve the head

[7,8]. The available epidemiologic evidence suggests that this is true also

for casualties sustained in OIF and OEF [9]. One remarkable improvement

in the medical outcome in these modern wars that may impact the preva-

lence of TBI is the very high survival rate among combat-injured United

States soldiers. At present, the killed/wounded ratio is less than 1 in 10,

which is a dramatic improvement over the 1 in 4 ratio of World War II.

The reason for this is the introduction of modern body armor coupled

with improved battlefield medical care. Modern military body armor is a sci-entific and engineering achievement [10]. When fitted with ballistic plates, it

can protect the wearer from most shrapnel and small arms bullets. Combat

helmets have also evolved and are similarly effective in mitigating injury

from common battle-related threats. Body armor and combat helmets

have undoubtedly reduced the incidence of injuries to the head, chest, and

abdomen, and injury severity [11]. These devices, however, are not perfect.

An unanticipated consequence is that more war fighters are surviving

what previously would have been fatal injuries, and other injury conditions

like TBI from explosive blast are now becoming relatively more prevalent[12]. Future efforts need to center on treatment methods that lead to im-

proved neurologic and functional recovery of survivors of TBI [13,14]. Bat-

tlefield medicine has also evolved. It is reported that most fatal injuries on

the battlefield result from injuries that are nonsurvivable in any setting

[15]. The modern triage and evacuation system is highly effective and far for-

ward medical providers are able to respond within seconds of an injury.

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They provide early effective care using tourniquets; hemostatic agents (eg,

HemCon bandages); and, importantly, arrange fast evacuation [16]. Modern

combat evacuation procedures used during OIF and OEF provide a modelfor delivery of forward critical care [17]. At the combat support hospital,

modern trauma care provided by appropriate specialty physicians and

nurses is available and includes CT scan, advanced emergency medical ser-

vices, early surgical intervention, and intensive care. Once stabilized, pa-

tients are evacuated out of the war zone to Europe or the United States.

This too has likely contributed to the remarkable survival rate of modern

war casualties.

The goal of the chain of medical providers is to provide early clinical sta-

bilization of the brain-injured patient, to arrest ongoing injury, to preserveand restore neurologic function, and to avoid secondary medical complica-

tions. In the field this first requires recognition that the brain is injured. Ap-

propriate management can be instituted and rapid evacuation initiated to

centers where neurointensivists, neurosurgeons, and other providers deliver

more advanced care.

Pathogenesis of traumatic brain injury

Classically, TBI is thought to have at least two phases. The first or initialinjury occurs as a direct result of the primary traumatic event. A second in-

jury phase occurs from multiple neuropathologic processes that can con-

tinue for days to weeks after the initial insult [18]. One of the principal

goals of neurocritical care is to intervene in a timely fashion to prevent

and disrupt secondary injury mechanisms.

Primary injury

Primary injury is immediate and not amenable to treatment. If severe,death can occur almost instantaneously. Typically, the damage that occurs

from this primary phase is often complete by the time medical care can be

instituted. The best way to mitigate primary injury is prevention. Education

and devices, such as motorcycle helmets, can contribute to reducing TBI

[19].

There are two classical types of head injury: closed head injury (CHI)

and penetrating TBI. In CHI, direct impact of neuronal tissue against the

bony vault, and shearing of neurovascular structures from rotational or re-

bounding forces, results in cell damage at the cell body and axon level. Inthe United States, most CHI is caused by motor vehicle accidents [20].

Other causes are falls, sporting event injuries, and assault. Motor vehicle ac-

cidents, which are high-speed collisions with very rapid deceleration, are

particularly injurious. Because the neuronal structures reside in a fluid-filled

compartment, they often lag behind the bony structure as it moves during

the sudden stopping of the body in motion. The structures strike both in the

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direct and opposite plane of motion against the inner bony table. This is the

basis of the coupcontre-coup lesion pattern, where contusional or other in-

jury to the brain is seen deep to the site of skull impact, and 180 degreesopposite the site of impact. If there is a rotational component, structures

torque and twist and shearing can occur. This is the cause of diffuse axonal

injury, commonly seen radiographically as punctuate hemorrhages on CT

or MRI after TBI.

In penetrating TBI, the calvarial vault is violated by a foreign body. That

body may be large and moving slowly as with a knife, or small and moving

rapidly as with a bullet. In both circumstances, the intruding body tears neu-

ral, vascular, and support structures as it traverses through the brain. If

moving at very high velocity (eg, supersonic), the vacuum created by theprojectiles wake gives rise to tissue cavitation. Fired projectiles, based on

shape and entry velocity, may cause more or less of this type of injury. Of

note, the temporary cavity may be several times larger that the projectile it-

self, and although transient, the expansion of tissue is sufficient to cause sig-

nificant irreversible damage.

Based on experience gathered during OIF and OEF, there is increasing

awareness of another class of head injury, referred to as blast TBI

(bTBI). The most common agent associated with modern bTBI is explosive

ordinance in the form of an improvised explosive device. bTBI may be con-sidered a subtype of CHI. Many warfighters, who are exposed to explosions,

suffer isolated bTBI and do not typically have penetrating injury to the

brain. Their injuries result from explosive forces transmitted into brain pa-

renchyma without breach of the calvarium. The mechanism of injury seems

to be different from other forms of CHI as described previously. The most

widely accepted opinion, although speculative, is that disruption of brain

function following exposure to an explosion is caused by a concussive pres-

sure wave. This concept may be an incomplete explanation for this mecha-

nism of injury, because an explosion is composed of more than pressurephenomenon and there are many other physical forces emanating from an

explosion, such as electromagnetic energy, acoustics, toxic fumes, and

others, that may be injurious to brain.

TBI may be further classified as focal or diffuse. Focal injuries occur at

the site of impact. Neurologic deficits are referable to those areas. The orbi-

tofrontal and anterior temporal lobes are most commonly affected because

of the location of the brain over the rough surface of the skull base. Because

of the tendency for head trauma to occur in an anteroposterior direction, the

brain moves similarly and is injured as it traverses over the skull base. Par-ticular vigilance must be made to identify the occurrence of delayed hema-

tomas, which can develop up to several days after the inciting trauma [21].

Diffuse axonal injury is shearing of axons in cerebral white matter, which

causes nonlateralizing neurologic deficits, such as encephalopathy. The con-

sequences of this type of injury can be delayed by up to 12 hours following

initial trauma [22]. Diffuse axonal injury can be identified as petechial white

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matter hemorrhages on CT and MRI studies after TBI; however, findings

may be subtle or absent on imaging. Recent evidence also suggests that

the incidence of diffuse axonal injury may be higher with forces occurringin a lateral orientation, as opposed to a frontal or oblique impact in CHI

[23].

Secondary injury

Therapeutic interventions are based on attenuating the secondary injury

phase of TBI. This phase of injury begins quickly after the primary phase

and can continue for a prolonged period involving dysfunction and death

of neurons and glial supporting structures. It is thought that the most signif-

icant burden of neurologic injury following TBI is related to this secondary

injury. A broad range of mechanisms are involved in secondary injury and

include hypoxia; ischemia; free radicals; excitatory amino acids; ion imbal-

ance (eg, calcium); temperature dysregulation; and inflammation [21]. Many

attempts at developing therapeutic strategies have focused on secondary in-

jury processes. Despite considerable research efforts, current clinical treat-

ment is largely confined to supportive measures with particular emphasis

on maintaining perfusion pressure and tissue oxygenation; minimizing intra-

compartment hypertension (eg, increased intracranial pressure [ICP]); and

treatment of cerebral edema. Scientific efforts to develop effective treatment

strategies aimed at improving meaningful clinical outcomes are ongoing.

Hypoxia and hypoperfusion are recognized as leading contributing fac-

tors to secondary brain injury. The injured brain is more susceptible to hyp-

oxic-ischemic states because of impaired cerebral vascular autoregulation.

The most susceptible areas are the hippocampus and border zone or water-

shed regions. It has been hypothesized that delayed neurologic compromise

can be attributed to the effects of ischemia [21]. Previous work has shown

that a single episode of hypotension where systolic blood pressures falls be-

low 90 mm Hg is associated with worse outcomes in severe TBI [24]. Diffuse

microvascular damage is associated with loss of cerebral vascular autoregu-

lation and loss of blood-brain barrier integrity. Laceration of microvascula-

ture exacerbates this injury. Microvascular damage contributes to the

prominent pattern of vasogenic edema observed after TBI [25].

Traumatic brain injury taxonomy

Classification and initial evaluation

TBI severity is classified as mild, moderate, or severe depending on the

level of consciousness on admission. Patients with mild TBI have an admis-

sion Glasgow Coma Score (GCS) of greater than 13. Mild TBI is frequently

referred to as concussion. These patients have experienced a brief (!30

minute) loss of consciousness, and presenting complaints include headache,



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confusion, and amnesia [26]. Following the acute period, a postconcussive

syndrome may develop, which usually lasts a few weeks but can persist up

to a year or more [5]. Postconcussive syndrome is a constellation of symp-toms that include headache, dizziness, difficulty concentrating, anxiety,

depression, and insomnia. The American Academy of Neurology has pub-

lished guidelines for concussion management that includes recommended

periods of recovery (Table 1). Other guidelines can also be used, such as

the Cantu Grading system and the Colorado Medical Society Guidelines,

which have been developed for sports-related TBI, but are widely applied

and meaningful for the management of both civilian and military patients

with head injury [2730].

Moderate TBI is defined as an admission GCS of 9 to 13, and is oftenassociated with prolonged loss of consciousness or neurologic deficit [31].

Clinically, patients with moderate TBI require hospitalization and may

need neurosurgical intervention. Moderate TBI is associated with a greater

likelihood of abnormal findings on craniocerebral imaging. These patients

may also develop a postconcussive syndrome.

Patients with GCS scores of 8 or less have severe TBI. They suffer from

significant neurologic injury. Typically, they have abnormal neuroimaging

(eg, CT scan revealing skull fracture or intracranial hemorrhage) [31]. These

patients require admission to the ICU, and institution of rapid measures forcontrol of the airway, mechanical ventilation, neurosurgical evaluation or

intervention, and ICP monitoring. Recovery is prolonged and usually in-

complete. A significant percentage of severe TBI patients do not survive

to 1 year [32].

A new classification for bTBI is being proposed by the Defense and Vet-

erans Brain Injury Center (DVBIC). The DVBIC conducts clinical research

on military-relevant TBI, such as bTBI. The increasing clinical experience

with this disease suggests that the existing severity definitions for classical

TBI may not be appropriate for bTBI. Mild bTBI is defined as loss of con-sciousness less than 1 hour and posttraumatic amnesia less than 24 hours.

Moderate bTBI is loss of consciousness for more than 1 but less than 24

hours and amnesia lasting more than 1 but less than 7 days. Severe bTBI

is loss of consciousness for more than 24 hours and amnesia for more

than 7 days. It should be understood that this new bTBI classification

Table 1

Glasgow coma score

Best motor response (M) Best verbal response (V) Best eye opening (E)

Follows commands 6

Localizes to pain 5 Oriented, alert 5

Withdrawal to pain 4 Confused, appropriate 4 Opens eyes spontaneously 4

Flexor posturing 3 Disoriented, inappropriate 3 Opens eyes to voice 3

Extensor posturing 2 Incomprehensible speech 2 Opens eyes to pain 2

No response 1 No response 1 No response 1

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was only recently proposed and has not yet gained wide acceptance in the

medical community [33,34].

Patients with mild or moderate TBI often have recovered or are rapidlyrecovering by the time they reach the emergency department. The critical el-

ement in their subsequent management is the duration of amnesia or any

history of a loss of consciousness. The American Academy of Neurology

grading scale for concussion is based primarily on these two aspects of

the neurologic history (Table 2). Longer periods of abnormal sensorium

are associated with higher grades of concussion. The higher grades necessi-

tate longer periods of convalescence and removal of the patient from an en-

vironment in which any further trauma is likely to occur. The DVBIC uses

this grading scale based on loss of consciousness and the presence of post-traumatic amnesia, but other factors including GCS and alteration of con-

sciousness are taken into account. Essentially, a patient with any degree of

alteration of consciousness or feeling dazed after exposure to head

trauma or concussive blast is classified and treated as having sustained at

least a mild TBI [35].

Second impact syndrome

A subsequent head injury during the vulnerable recovery period may re-

sult in second impact syndrome. Second impact syndrome is seen mostly

in children and adolescents and has been associated with significantly worse

clinical outcomes. In severe instances, coma can rapidly develop following

Table 2

American Academy of Neurology concussion management

Grade 1 (mild)

Remove from duty/work/play

Examine immediately and at 5-min intervals

May return to duty/work if clear within 15 min

Grade 2 (moderate)

Remove from duty for the rest of the day

Examine frequently for signs of central nervous system deterioration

Physicians neuroexamination as soon as possible (within 24 h)

Return to duty after 1 full asymptomatic week (after being cleared by physician)

Grade 3 (severe)

Take to emergency department

Neurologic evaluation, including appropriate neuroimaging

Consider hospital admission

Grade of concussion Return to play/work

Grade 1 (first) 15 min

Grade 1 (second) 1 wk

Grade 2 (first) 1 wk

Grade 2 (second) 2 wk

Grade 3 (first) (brief LOC) 1 wk

Grade 3 (first) (long LOC) 2 wk

Grade 3 (second) 1 mo

Grade 3 (third) Consult a neurologist



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a second injury, often within minutes. The exact mechanisms by which sec-

ond impact syndrome occurs is not fully understood but it is postulated that

the additional injury leads to an exacerbation in already impaired cerebralautoregulation, diffuse cerebral edema, and intracranial hypertension. For-

tunately, second impact syndrome is uncommon in its most severe form.

When it occurs, however, there is up to 50% mortality.

Clinical management

Early intervention

An organized team approach is essential to proper management of TBI.The initial goals of care should be immediate attention to airway and cardio-

pulmonary function (ABCs); early identification of the potential for TBI in

any trauma victim; and minimization of secondary insults, such as hypoxic-

ischemic injury. In the first few minutes, nonphysician health care providers,

such as emergency medical technicians, can make rapid initial neurologic

evaluations using a standardized grading scheme, such as the GCS. In the

absence of a formal GCS, this information can often be elicited from first

responder data or interviews. The GCS is important in categorizing and tri-

age of TBI patients, and providing a quantifiable measure of impairment,which can help decide early management sequences in an organized algo-

rithm. This initial examination also helps guide prognosis for the outcome

of severe TBI.

It is crucial that prehospital providers optimize perfusion and oxygena-

tion, because it is well recognized that the duration and severity of hypoxia

and hypotension in this critical early period has dramatic consequences on

clinical outcome [14,36]. Avoidance of hypotension (systolic blood pressure

!90 mm Hg) and maintenance of adequate oxygen saturation (O90%) are

level II and level III recommendations from the Brain Trauma Foundation,respectively [37].

In many patients with moderate and all patients with severe TBI, airway

protective mechanisms are impaired and tracheal intubation should be per-

formed. The cervical spine should be immobilized with a rigid neck collar

and the head placed in midline position and elevated to 30 degrees. The

neck collar serves not only to protect the cervical spine until appropriate im-

aging can be performed to rule out instability, but it also keeps the head

midline to avoid compromising venous drainage, which can increase ICP.

Surgical management may be beneficial in selected patients with traumaticlesions. There are many injuries that do not warrant surgical intervention and

management is primarily medical. Diffuse or disseminated injuries, such as

diffuse axonal injury and contusional injury, typically are not managed sur-

gically. Conditions in which neurosurgery is warranted are those related to

breach of the calvarium, presence of expanding intracranial hematoma, or

malignant cerebral edema. Depressed skull fractures often requires elevation.

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Hematomas, in particular symptomatic subdural and epidural hematomas,

may need evacuation. Subdural hematoma is the basis of approximately

50% of hospital admissions for head injury; epidural hematoma accountsfor only 3% [34,38]. When there is a skull fracture, especially at the tempor-

oparietal junction, the incidence of epidural hematoma tends to increase,

most commonly because of disruption of the middle meningeal artery.

Decompressive craniectomy is an emerging clinical management ap-

proach in the early intervention and management of TBI. The reported expe-

rience to date is conflicting. In a study of 57 young patients with severe TBI

(age!50), early decompressive craniectomy was associated with a good out-

come, defined as social rehabilitation, in 58% of patients. The authors re-

ported a relatively low mortality of less than 20% [39]. A retrospectiveFrench study was able to show a similar outcome in only 25% of severe

TBI patients [40]. The more recent Early Decompressive Craniectomy for Se-

vere TBI study reported that patients who underwent decompressive craniec-

tomy for uncontrolled ICP had significant improvement in ICP control and

better clinical outcomes compared with historical controls [41]. This is coun-

tered, however, by a retrospective study of the Trauma Coma Data Bank

that suggested there was no significant improvement with craniectomy [42].

One of the difficulties in interpreting the available data is the lack of agree-

ment regarding surgical technique (release the dura or not, timing of surgery,cut-off age, and TBI severity on presentation) [43]. At present, the Random-

ized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation

of Intra-Cranial Pressure trial is under way. This is a large multicenter trial

in Europe comparing decompressive craniectomy with medical management

in TBI. One application of decompressive craniectomy is treatment of severe

bTBI. United States military neurosurgeons report favorable outcomes in

bTBI patients who undergo early decompressive craniectomy [33,44].

Neurologic intensive care unit management of severe traumaticbrain injury

After initial emergency care, patients with severe TBI require admission

to the ICU. Limited available data suggest that outcomes may be improved

when specialized neurologic intensive care teams or algorithms are present

to guide management [45]. The presence of other traumatic injuries may re-

quire a broad multidisciplinary approach for these patients, including input

from trauma, orthopedic, craniofacial, ophthalmologic, and other specialty

physicians.

Continuous neurologic evaluations

There is no better diagnostic approach than clinically to examine the pa-

tient, and track changes over time with serial evaluations. In the acute pe-

riod, these evaluations may be as often as every hour with increasing



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intervals as the patients condition stabilizes. If needed, ICP and cerebral

perfusion pressure (CPP) measurements should be made continuously.

Even in the presence of ICP monitoring, the importance of the clinical ex-amination and neurologic assessment cannot be overstated. Generally, the

peak period of cerebral edema is from 48 to 96 hours after TBI. Thereafter,

this resolves and clinical improvement should follow with improved ICP

control.

Imaging and intracranial pressure monitoring

Neuroimaging with a noncontrast enhanced CT scan should be done as

soon as possible in the emergency department. The goal is to identify asearly as possible any lesions amenable to neurosurgical intervention. If

such a lesion is not identified, the patient should be admitted to the ICU

for further treatment. If the patient has a GCS of 8 or less, any acute abnor-

mality on CT, a systolic pressure of less than 90 mm Hg, or age greater than

40 years, an ICP monitoring device should be placed. The external ventric-

ular drain provides the most accurate and reliable data and also provides

a means to control ICP by cerebrospinal fluid removal. Other monitoring

options, which do not have this treatment advantage but are less invasive,

include the subdural bolt and fiberoptic catheter. If there is any degree ofhydrocephalus on imaging studies, an external ventricular drain is the best

choice for monitoring and treating ICP.

Increased intracranial pressure

Increasing volume within a closed rigid container, such as the skull, inev-

itability leads to increasing pressure within that confined space. The in-

creased pressure, particularly if it is compartmentalized, compresses vital

structures, such as brain and blood vessels. If blood vessels are compressed,then ischemia ensues. If brain is compressed, ICP can rise significantly and if

allowed to progress can lead to herniation. General management of in-

creased ICP and herniation includes control of the airway; elevation of

the patients head to 30 degrees; and administration of mannitol, 0.5 to

1 g/kg over 10 minutes. Another option, particularly for patients with com-

promised intravascular volume, is to administer hypertonic saline. Recent

data suggest that an intravenous bolus of 23.4% saline, 30 mL, given over

10 to 15 minutes, may effectively reverse herniation and decrease ICP,

with only transient hemodynamic repercussions [46]. Hyperventilationmay also be considered, but only as an emergent, temporary intervention,

because prolonged hyperventilation has been associated with exacerbation

of cerebral ischemia [47]. Short durations of hyperventilation are acceptable

as a temporizing measure until other (surgical, hyperosmolar) means of

managing increased ICP are available. If hyperventilation is continued for

longer than 12 hours, metabolic compensation negates the ameliorative

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effects of respiratory alkalosis caused by a hypocapnic state and continued

hyperventilation may be harmful. Induced hypothermia for TBI remains

controversial because of the lack of compelling outcome-modifying resultsfrom clinical trials. Eventually, it may prove to be beneficial in subsets of

patients [14,48,49]. Recent animal data show promise for induced hypother-

mia with improved neurophysiologic metrics in asphyxial (nontraumatic)

brain injury [50]. Current use of prophylactic hypothermia for severe TBI

is not substantiated, however, based on a level III recommendation from

the Brain Trauma Foundation [37].

The use of hypertonic saline for cerebral edema merits further discussion.

A single dose of 23.4% hypertonic saline can reduce ICP. There is some ev-

idence to suggest that this is as effective in lowering ICP and may possiblyhave a longer duration of effect compared with mannitol [51]. This concen-

tration is a low-volume infusion, and may be beneficial in cases where the

volume status of the patient dictates caution with large infusions. The ben-

efit of hypertonic saline is that it helps maintain a high serum sodium con-

centration and thereby promotes water movement from the intracranial

compartment into the vasculature. When used clinically, 2% saline solutions

can be given by a peripheral line, but 3% and higher concentrations of saline

should be administered through a central venous catheter to minimize ve-

nous phlebitis. When used as a continuous infusion, hypertonic saline solu-tions are commonly prepared as a 1:1 ratio of sodium acetate to sodium

chloride so as to minimize the development of hyperchloremic metabolic ac-

idosis. The use of hypertonics has not received a level III or better recom-

mendation for use in trauma-induced increased ICP [35,5254].

Sustained treatment of increased intracranial pressure

Current guidelines recommend maintaining the ICP less than 20 mm Hg

and the CPP greater than 60 mm Hg. If ICP remains poorly controlled afterefforts described previously, 23.4% saline may be administered through

a central venous catheter. If this should also be unsuccessful in reduction

of ICP, consideration should be made toward pharmacologic coma or sur-

gical decompression. The postulated effect of pharmacologic coma on ICP is

through reduction of cerebral metabolism (CMRO2) with concomitant re-

ductions in cerebral blood flow and reduced tissue oxygen demand. The

most commonly used agent for pharmacologic coma, pentobarbital, can

be administered intravenously at a loading dose of 5 mg/kg, followed by

an infusion of 1 to 3 mg/kg/h; a high-dose regimen may also be used withan intravenous bolus dose of 10 mg/kg over 30 minutes followed by 5

mg/kg/h infusion for 3 hours, followed by 1 mg/kg/h titrated to either burst

suppression on continuous electroencephalogram monitoring or a reduction

in ICP. Another option for pharmacologic coma is propofol, which is given

in an intravenous loading dose of 2 mg/kg, followed by a titrated infusion of

up to 200 mg/kg/min. The use of propofol for this clinical indication is



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controversial. Propofol has been associated with the development of a pro-

pofol infusion syndrome of renal failure, hyperkalemia, myocardial failure,

and metabolic acidosis, often resulting in death. The mechanism for this isnot fully understood. If these efforts fail to control ICP, or as an alternative

to pharmacologic coma, decompressive craniectomy or lobectomy may be

considered. Should the patient be unsuitable for surgery and if the ICP ele-

vation remains recalcitrant, then the patients condition is likely terminal

[37,5557].

Recent experience with head injuries sustained in combat has suggested

a new paradigm for the early surgical management for bTBI and TBI. Ex-

perience has shown that early hyperemia and severe cerebral edema occurs

frequently in the setting of a significant blast injury; a decompressive cra-niectomy permits the swelling brain to avoid compression by the bony skull.

From a practical military standpoint, craniectomy provides an additional

measure of safety for ICP control through the air-evacuation process where,

at times, ICP management can be challenging. Another benefit of early de-

compressive craniectomy is that it may obviate the need to use more conven-

tional methods to control ICP, such as pharmacologic coma, which is

difficult to execute in a deployed and hostile setting because of the limited

number of neurologic critical care specialists and lack of electroencephalo-

gram support in a war zone. In this setting, decompressive craniectomymay be the most practical, if seemingly aggressive, approach [33,38,44].

Hemodynamic management

The recommended CPP goal is greater than 60 mm Hg. To achieve this,

fluid resuscitation to euvolemia is the first step. Hypo-osomolar solutions,

such as 0.50 normal saline or 5% dextrose in water, are to be avoided. A

commonly used hyperosmolar fluid is normal saline. Other options as clin-

ically warranted are hypertonic saline (eg, 2% or 3% sodium solutions); col-

loids; and blood products. If CPP cannot be maintained with intravenousfluids alone, vasoactive pharmacologic agents, such as norepinephrine or

phenylephrine, may be required. These two agents are preferred because

they have minimal effects on cerebral vasomotor tone. Invasive hemody-

namic monitoring with a central venous pressure catheter and an arterial

catheter may be needed. It should be remembered that barbiturates and pro-

pofol are myocardial depressants and peripheral vasodilators, and invasive

hemodynamic monitoring and support are often necessary when pharmaco-

logic coma is induced.

Vasospasm and pseudoaneurysms after traumatic brain injury

Vasospasm is a common finding after bTBI. Recent data by Armonda

and colleagues [58] reveal that up to 50% of patients suffering moderate

to severe bTBI developed cerebral vasospasm. Transcranial Doppler studies

in theater reveal that vasospasm can develop early, often within 48 hours of

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injury [59]. Vasospasm can also present later in postinjury phase, typically

10 or more days after initial insult.

Penetrating head injury and bTBI may be associated with pseudoaneur-ysm formation. Such blast-related pseudoaneurysms have been found to ex-

pand despite endovascular ablation attempts. Patients with such lesions

often require craniotomy and aneurysm clipping [58]. The accuracy of non-

invasive forms of vascular imaging, such as MR angiogram and CT angio-

gram, in diagnosing pseudoaneurysms may be limited. Furthermore, many

military patients have retained fragments that obviate the use of MRI. The

military causalities in OIF and OEF evaluated at Walter Reed Army Med-

ical Center and the National Naval Medical Center undergo four-vessel ce-

rebral angiography as the favored diagnostic approach.

Sedation

If the TBI patient is agitated, evaluation must be made to determine

whether the patient is in pain, hypoxic, delirious, or poorly tolerating me-

chanical ventilation. If pain is a concern, then a narcotic analgesic, such

as fentanyl or other short-acting medication, should be administered. Lon-

ger-acting narcotics, such as morphine or hydromorphone, are discouraged

even though they can be easily reversed by naloxone. Administration of nal-

oxone should not be done routinely to facilitate a neurologic examination

because of the likely discomfort that this may cause a victim of recent

trauma. Preferably, a short-acting narcotic infusion is held for a brief

time, which allows reassessment of neurologic status. If delirium or agitation

alone is the issue, then haloperidol or an atypical antipsychotic can be used.

In the acute period after TBI, haloperidol is nonsedating, which preserves

the neurologic examination. In the more subacute period, when observation

of subtle examination changes is not as crucial, atypical antipsychotics, most

of which do not have haloperidols nonsedating property but are better tol-

erated, may be a better choice for controlling agitation. Recent work in an-imals has suggested that, in addition to typical and atypical neuroleptics

dissimilar side effect profiles, there may be differences in their use and effect

on long-term neurologic outcomes, although this area needs further research

[60].

Avoidance of other exacerbating complications

Hypoxic states, seizures, and fevers are to be avoided. Maintaining PaO2

at approximately 80 to 100 mm Hg is sufficient; there is no documented ben-efit to higher levels of oxygen but there is potential for toxicity.

Studies have demonstrated that phenytoin is beneficial in reducing the

risk of seizures during the first week after TBI [61]. It has not been shown

to prevent late seizures (ie, those developing after 7 days). Because fewer

than 50% of TBI patients develop late seizures, the recommended approach

is to stop seizure prophylaxis after the first 7 days and only reinstitute



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treatment should late seizures manifest. The potential for cognitive side ef-

fects of phenytoin make prolonged prophylactic use of this medication less

attractive. Alternatives abound, including carbamazepine and valproate,and levetiracetam, which is available in an intravenous or enteric form

[62]. This medication is commonly used in the authors institution for this

indication.

Hypertension, tachycardia, and fever and dystonia may be a sign of au-

tonomic dysregulation syndrome, frequently seen in TBI, although alterna-

tive explanations must be ruled out before accepting this diagnosis of

exclusion. Bromocriptine, propanolol, and opioids can be used to treat

this condition.

Temperature dysregulation is common in TBI, and fever from any causegreatly increases cerebral metabolism and should be treated with the use of

antipyretic interventions, such as acetaminophen and cooling blankets.

Other modalities of induction of normothermia include skin-applied gel

cooling systems and intravenous methods. The use of prophylactic hypo-

thermia in brain trauma has to date failed to show a benefit in terms of post-

injury outcome measurements, and is currently not recommended [63].

Other important management considerations include prevention of gas-

tric stress ulcer, venous thromboembolism, and decubitus ulcers. Gastric

stress ulcers may be prevented using such agents as H2 antagonists or protonpump inhibitors. These medications should be routinely used in all severe

head injury patients. TBI patients are at high risk for developing deep ve-

nous thrombosis with subsequent thromboembolism. The optimal approach

in severe TBI with intracranial hemorrhage is uncertain. Sequential com-

pression devices on the lower extremities are minimally invasive and are

not associated with any notable adverse effects. The optimal timing of intro-

duction of unfractionated or low-molecular-weight prophylactic heparin is

less clear. If there are no contraindications to heparin use, however, then

treatment should be started as soon as possible, ideally within the first 36hours of injury [64]. The routine placement of inferior vena cava filters is

controversial, and placement is currently supported only by a level III rec-

ommendation with a GCS score of greater than 8 and contraindications to

any anticoagulants [64].

Prognosis of traumatic brain injury

Clinically, the most useful prognostic indicator following TBI is the neu-rologic examination at presentation. Classically, it has been taught that the

better the initial neurologic examination, the less likelihood of severe neuro-

logic damage [65]. For patients with severe TBI, the initial GCS is the most

commonly used prognostic indicator (see Table 1). The lower the initial

GCS score, the less likely a patient has meaningful neurologic or functional

outcome. Comparisons have been made based on historical data obtained

422 LING & MARSHALL


15/18

for anoxic or non-TBI from cardiac arrest, but this mechanism of injury and

patient population (ie, age) is quite different [66]. A prospective study with

long-term outcomes measurements for severe TBI and bTBI has beenneeded for some time. Recent publication of the CRASH trial has associ-

ated long-term (6 month) outcomes in TBI with age, GCS score, pupil reac-

tivity, and the presence of extracranial injury, in addition to radiographic

and other data collected for more than 8000 TBI patients in multiple coun-

tries. Interestingly, advancing age was most associated with poor outcome in

high-income countries, and low GCS was most associated with poor out-

come in low-middle income countries. The absence of pupil reactivity was

the third strongest predictor of poor outcome in high- and low-income

countries. Radiographically, obliteration of the third ventricle and midlineshift was most likely to be associated with early mortality (14 days), and

nonevacuated hematoma was most likely to be associated with poor out-

come at 6 months [67]. Recent work using diffusion-weighted MRI corre-

lated with 6 to 12 months Glasgow Outcomes Scale shows MRI as

a helpful addition to prognostication in TBI [68]. Other modalities including

MRI diffusion tensor imaging have been helpful in prognostication in TBI

[69].

Summary

TBI is a common and complex clinical entity and deserves better and con-

tinued research on interventions and initial treatment postinjury. Blast-

related TBI is increasingly recognized and characterized in part because of

the militarys current demographics of casualties sustained in OIF and

OEF. Treatment of moderate to severe TBI and bTBI is optimally delivered

in the ICU, where the first few hours and days after injury are likely to have

a significant impact on patient outcome. Mortality following TBI has beengreatly reduced, although morbidity from TBI and bTBI remains a signifi-

cant problem. With respect to bTBI, a comprehensive epidemiologic study

is desperately needed to determine the prevalence, risk factors, natural his-

tory, and outcomes of this condition. Additionally, a better comprehensive

clinical description of bTBI with strict diagnostic criteria could greatly facil-

itate study of this illness.

Current medical management of TBI is articulated on minimizing sec-

ondary injury by optimizing cerebral perfusion and oxygenation and pre-

venting or treating nonneurologic morbidity. There are major medicalresearch efforts examining the underlying mechanisms of secondary brain

injury, which provides hope for effective therapies in the future. Presently,

a number of promising therapeutic modalities are undergoing clinical trials,

and as new pharmacologic and medical approaches are introduced, there

will be increasing opportunity to treat these patients and improve their neu-

rologic outcomes.



16/18

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