Traumatic brain injury

Ma. Cristy L. Exconde, MD, FPOGS

 Topics

-definition
-causes
-pathophysiology
-severity
-diagnosis
-complications
-management
 Definition of TBI

“An insult to the brain, not of degenerative or

congenital nature caused by an external physical
force that may produce a diminished or altered state
of consciousness, which results in an impairment of
cognitive abilities or physical functioning. It can also
result in the disturbance of behavioral or emotional
functioning.”
 Causes

An outside force

impacts the head
causing the brain to
move

A direct blow to the

head

A rapid acceleration and

deceleration of the head
Traumatic brain injury (TBI) is the leading cause of
death for all age groups, contributing to over 60% of
trauma-related deaths.
The primary goals of management in TBI are to
minimize cerebral edema, intracranial pressure
(ICP), and to optimize cerebral perfusion pressure
(CPP) thereby decreasing the incidence of secondary
injury
 Pathophysiology

TBI may be divided into primary injury and

secondary injury.

Primary injury is induced by mechanical force

and occurs at the moment of injury.

Secondary injury is not mechanically induced. It

may be delayed from the moment of impact, and it
may superimpose injury on a brain already
affected by a mechanical injury.
 Primary injury:

The 2 main mechanisms that cause

primary injury are:

Contact (as an object striking the head or the

brain striking the inside of the skull)
Acceleration-deceleration.
Primary injury due to contact may result in;
injury to the scalp, fracture to the skull and
surface contusions.

Contusions are distinct areas of swollen brain

tissue,typically found on the poles of the
frontal lobes, the inferior aspects of the frontal
lobes, the cortex above and below the
operculum of the sylvian fissures, and the
lateral and inferior aspects of the temporal
lobes.
Primary injury due to acceleration-deceleration
results from unrestricted movement of the head and
leads to shear, tensile, and compressive strains.

These forces can cause intracranial haematoma

or diffuse axonal injury (injury to cranial nerves
and the pituitary stalk.
Intracranial haematoma is the most common cause of
death and clinical deterioration after TBI. Haematomas
may be:
Epidural haematomas caused by fracture of the
temporal bone and rupture of the middle meningeal artery,
clotted blood collects between the bone and the dura.It can
grow quickly creating pressure against the brain tissue.
Subdural haematomas are usually caused by rupture of
the bridging veins in the subdural space. They can grow
large enough to act as mass lesions, and they are associated
with high morbidity and mortality rates.
Subarachnoid haematomas result from damage to
blood vessels in the posterior fossa stalk.
 Diffuse axonal injury (DAI) is one of the most common and
important pathologic feature of TBI.
It constitutes mostly microscopic damage, and it is often not
visible on imaging studies.
The main mechanical force that causes DAI is rotational
acceleration of the brain, resulting in unrestricted head
movement.
Rotational acceleration produces shearing and tensile forces, and
axons can be pulled apart at the microscopic level.
Microscopic evaluation of the brain tissue often shows numerous
swollen and disconnected axons.
Rapid stretching of axons is thought to damage the axonal
cytoskeleton and, therefore, disrupt normal neuron function.
Secondary injury:
It may occur hours or even days after the inciting
traumatic event.
Injury may result from impairment or local declines
in CBF after TBI as a result of local edema,
haemorrhage or increased ICP.
As a result of inadequate perfusion, cellular ion
pumps may fail, causing a cascade involving
intracellular calcium and sodium which may
contribute to cellular destruction.
Excessive release of excitatory amino acids, such as
glutamate and aspartate, exacerbates failure of the
ion pumps.
As the cascade continues, cells die, causing free
radical formation, proteolysis, and lipid
peroxidation.
These factors can ultimately cause neuronal death.
 Pathophysiology

• 2 distinctive endpoints (secondary neuronal injury)

1. energy-independent cellular necrosis (membrane cell
lysis, edema, inflammation)
2. energy-independent apoptosis (leading to cell
shrinkage and cell membrane dissolution)
• Key event in the secondary brain injury:
LOSS OF IONIC HOMEOSTASIS
• Role of calcium: >stimulates excessive release of
glutamate and aspartate
> stimulate activation of autodestructive
enzymes. (phospholipases, endonucleases, proteases)
 Pharmacologic Management of TBI

• Hyperosmolar therapy
1. Mannitol – effective in lowering ICP
0.25-1g/kg BW
2. Hypertonic saline solution – effective,
no guideline exist
 Pharmacologic Management of TBI

• Pre-intubation antibiotics to reduce

incidence of pneumonia
• Prophylactic antibiotic prior to ventricular
catheter insertion not recommended
 Desired Outcome

• Goal of TBI Management

• Reduction in mortality and morbidity
• Optimize long-term functional outcome
• Short-term Therapeutic Goals for TBI Patients
• ABC
• Maintain balance between CDO2 and CMRO2
• Prevent/attenuate secondary neuronal injury
• Prevent/treat associated medical complications
 Drug Dosing and Monitoring of TBI Patients

• Refer to Table 58-3

 Personalized Pharmacotherapy

• Points to consider:
• TBI patients have larger Vd
• More rapid drug hepatic clearance
• Wide interpatient variability in the efficacy of
pharmacologic and non-pharmacologic
interventions un ICP control
• DVT prophylaxis is highly personalized
depending on:
a. CT findings
b. Neurologic process
c. ICP control
d. Possible need for surgery
TABLE 58-4  Evaluation of Therapeutic Outcomes
To summarize causes of secondary brain injury:
Hypotension
Hypoxaemia
Hypercarbia
Hyperthermia
Hyperglycaemia
Hypoglycaemia
Hyponatraemia
Seizures
Infection
 Severity

Head injuries can be classified into mild,

moderate, and severe.
The Glascow Coma Scale (GCS),is the most
commonly used system for classifying TBI severity;
TBI with a GCS of 13 or above is mild, 9–12 is
moderate, and 8 or below is severe.
Other classification systems are also used to help
determine severity; duration of post-traumatic
amnesia (PTA), and loss of consciousness (LOC).
 Severity of traumatic brain injury

GCS PTA LOC

Mild 13-15 Less than 0-30 min.

1 day

Moderate 9-12 1-7 days 30min.-

24hrs.
Severe 3-8 More than More than
7 days 24hrs.
 Signs and symptoms

Symptoms are dependent on the injury's severity:

• With mild TBI, the patient may remain conscious or may lose
consciousness for a few seconds or minutes.
• Other symptoms of mild TBI include; headache, vomiting, nausea, lack
of motor coordination, dizziness, difficulty balancing, lightheadedness,
blurred vision or tired eyes, ringing in the ears, bad taste in the mouth,
fatigue or lethargy, and changes in sleep patterns.
• Cognitive and emotional symptoms include; behavioral or mood
changes, confusion, and trouble with memory, concentration, attention,
or thinking.
A person with a moderate or severe TBI may have a headache
that does not go away, repeated vomiting or nausea, convulsions,
an inability to awaken,dilation of one or both pupils,slurred
speech, aphasia , dysarthria, weakness or numbness in the limbs,
loss of coordination, confusion, restlessness, or agitation.
Common long-term symptoms of moderate to severe TBI are
changes in appropriate social behaviour, deficits in social
judgment, and cognitive changes, especially problems with
sustained attention, processing speed, and executive functioning.
When the pressure within the skull,ICP rises too high, it can be deadly.
Signs of increased ICP include decreasing level of consciousness, paralysis or
weakness on one side of the body, and a blown pupil, one that fails to constrict in
response to light .
Cushing's triad, a slow heart ratewith high blood pressure and respiratory
depressionis a classic manifestation of significantly raised ICP.
Anisocoria, unequal pupil size, is another sign of serious TBI.
Abnormal posturing, a characteristic positioning of the limbs caused by severe
diffuse injury or high ICP, is an ominous sign.
Small children with moderate to severe TBI may have some of these symptoms.
Other signs seen in young children include persistent crying, inability to be
consoled, listlessness, refusal to nurse or eat and irritability.
 Diagnosis

Neurological examination and assigning a GCS

Score.
Neuroimaging helps in determining the diagnosis
and prognosis and proposed treatment.
The preferred radiologic test in the emergency
setting is computedtomography (CT): it is
quick, accurate, and widely available.
Followup CT scans may be performed later to
determine whether the injury has progressed.
Magnetic resonance imaging (MRI) can show
more details than CTas detecting injury
characteristics such as diffuse axonal injury.
However, MRI is not used in the emergency
setting. are still used for head injuries that are so
 X-rays
mild that they do not need imaging or severe
enough to merit the more accurate CT.
Angiography may be used to detect blood vessel
pathology.
Electroencephalography and transcranial
doppler may also be used.
 Complications

Posttraumatic seizures;
frequently occur after moderate or severe
TBI, they are usually general or partial.
Immediate seizures occur in the first 24 hours.
Early seizures occur in the first 2-7 days.
Late seizures occur after 7 days.
Temkin showed that prophylactic use of phenytoin is
effective during the first week after TBI.
He recommended discontinuation after 1 week if no
seizures develop because of its lack of effect in
preventing late seizures.
 Hydrocephalus

Hydrocephalus is characterized as communicating or

noncommunicating; Noncommunicating
hydrocephalus occurs secondary to an obstruction in
the ventricular system before the point at which CSF
exits the fourth ventricle.
Communicating hydrocephalus is the most
common form after TBI and occurs when the
obstruction is in the subarachnoid space.
 Deep vein thrombosis

-DVT is common in persons with TBI, with an

incidence as high as 54%.
-Risk factors for DVT include; immobility, lower
extremity fracture, paralysis, and disruption in
coagulation and fibrinolysis.
-DVT may cause pulmonary embolism,
postthrombotic syndrome or recurrence.
-DVT best detected by venous Doppler
ultrasonography and contrast-enhanced
venography.
-Prophylaxis for DVT should be started as soon as
possible.
Heterotopic ossification is described as ectopic bone
formation in the soft tissue surrounding the joints,in
TBI, its incidence is 11-76%.
-It causes joint pain and decreases range of motion ,it
is often associated with low-grade fever, peri-
articular swelling, peri-articular warmth, and peri-
articular erythema.
-The risk of heterotopic ossification is greatest during
the first 3-4 months after injury.
Spasticity is defined as velocity-dependent increase
in tone.
It is found in an estimated 25% of patients with TBI.
-First-line treatment for spasticity is correct
positioning of the involved body segment and
exercises.
-Second-line treatment include splinting, casting and
other modalities.
GIT and urinary tract complications remain
among the most common sequelae in patients with
TBI.
-Most frequent GIT complications are; stress ulcers,
dysphagia, bowel incontinence, and elevated levels of
liver function tests. -
Urinary tract complications include; urethral
strictures, infections, and urinary incontinence.
Posttraumatic agitation is common after TBI.
Furthermore, aggression was consistently
associated with depression.
Insomia is common in TBI patients. They may
have nighttime awakenings and longer sleep-onset
latency.
Posttraumatic headache in 38%.
Posttraumatic depression in 40% after TBI, it
is further associated with cognitive decline, anxiety
disorders, substance abuse, dysregulation of
emotional expression, and aggressive outbursts.
 management
Initial Evaluation
All patients who present with suspected TBI should
undergo a rapid primary and secondary survey with
thorough evaluation of their airway, breathing, and
circulation.
Airway patency and adequate oxygenation and ventilation
are paramount to avoiding secondary brain injury .
The patient’s cervical spine should be immobilized until
cervical spine injury is ruled out. Urgent intubation to
secure the patient’s airway should be considered in any
patient who presents with a GCS < 8 or in those who are
unable to protect
Intravenous their airway.
access should be rapidly established
. Bedside glucose testing should be performed in all unconscious patients and
hypoglycemia rapidly treated if present. Thiamine (100 mg) should be administered in
patients at risk for nutritional deficiency.

If opioid toxicity is suspected (e.g., history of illicit drug use, apnea, bradypnea, small
pupils), naloxone 0.4 mg IV should be administered and repeated as necessary, up to 4
mg.

Appropriate laboratory tests [serum electrolytes, CBC with platelets, coagulation studies,
arterial blood gas, urinalysis, and urine toxicology / alcohol level (as appropriate)]
should be performed.

If definitive neurosurgical care cannot be provided at the initial presenting institution,

transfer to a higher level of care should be facilitated in a rapid fashion to preserve the
“Gold Hour” and optimize the patient’s outcome. Certain key resuscitative interventions
should initiated at the referring facility however to minimize secondary cerebral injury
 Management

Monitoring:
This is essential in severe TBI.
It includes; ECG, invasive arterial blood pressure,
pulse oximetry, central venous pressure, urinary
catheter, naso-gastric vs oro-gastric tube (in case of
base skull fracture), frequent neurological
examination, temperature and capnography.
 Resuscitation of Blood Pressure
& Oxygenation

Guideline
Hypotension (SBP < 90 mm Hg) or hypoxia
(apnea of cyanosis in the field or a PaO2 < 60 mm
Hg)must be scrupulously avoided, if possible, or
corrected immediately.
Hypotension (SBP < 90 mm Hg) occurred in 35%
of patients and was associated with a two fold increase in
mortality.
Option
The mean arterial pressure should be maintained
above 90 mm Hg throughout the patient’s course.
 Maintenance of cerebral perfusion
pressure(CPP):

This is achieved by maintaining MAP above 90mmHg

and preventing increases in ICP,to be between
20-25mmHg.
CPP = MAP –ICP
Cerebral Perfusion Pressure
Cerebral Perfusion Pressure should be
maintained at a minimum of 70 mm Hg.
Maintaining MAP
Treating hypovolaemia by 0.9% NaCl/ colloids/P-
RBCs/FFP as indicated.
Avoid glucose containing fluids unless there is
hypoglycaemia (blood sugar should be between 4-7
mmols).
Start early enteral feeding as,TBI patients have
induced hypermetabolic
and hypercatabolic state resulting in increased energy
and protein.
Use inotropes (noradrenaline- dopamine), if other
causes of hypotension are treated.
 Initial Management

Option
The first priority for the head injured patient is
complete and rapid physiologic resuscitation.
No specific treatment should be directed at
intracranial hypertension in the absence of signs
of transtentorial herniation or progressive
neurologic deterioration not attributable to
extracranial explanations.
 Indications for ICP Monitoring

Guideline
ICP monitoring is appropriate in severe head injury
patients with an abnormal CT, or a normal CT scan if 2 or
more of the following are noted on admission:
SBP < 90 mm Hg
Age > 40 years
Uni-/Bilateral motor posturing

Risk of intracranial hypertension (with normal CT) increased to

60% if two or more of the following were noted:
1) Age over 40 years
2) SBP < 90 mm Hg
3) motor posturing
 Monitoring of increase in ICP

CT scan should be done on admission and repeated

whenever there is change in symptoms or signs.
Frequent neurological examination is essential.
Hourly recording of GCS, hourly recording of pupil
size and reaction.
Monitoring ICP if available.
 ICP Monitoring Technology

Recommendation
In the current state of technology, the ventricular
catheter connected to an external strain gauge is
the most accurate, low cost, and reliable method
of monitoring ICP. It also allows therapeutic
CSF drainage.
ICP transduction via fiberoptic or strain gauge
devices placed in ventricular catheters provide
similar benefits but at a higher cost.
 Controlling ICP

ICP Treatment Threshold

Guideline
ICP treatment should be initiated at an upper
threshold of 20 - 25 mm Hg.

Raised ICP leads to secondary brain injury.

It is treated by; osmotherapy, analgesia, sedation,
optimal ventilation, surgical and positioning of
patient.
Critical Pathway for Treatment of Intracranial
Hypertension in the Severe Head Injury Patient
(Treatment Option)

Insert ICP Monitor

Maintain CPP  70 mmHg

YES Intracranial Hypertension?* NO

Ventricular Drainage (if available)

YES Intracranial Hypertension? NO

Consider May Repeat Mannitol Carefully
Repeating Mannitol (0.25 - 1.0 g/kg IV) if Serum Osmolarity Withdraw
CT Scan < 320 mOsm/L & ICP Treatment
Intracranial Hypertension? Pt euvolemic
YES NO

Hyperventilation to PaCO2 30 - 35 mmHg

YES Intracranial Hypertension? NO

Other Second •  Hyperventilation to PaCO2 < 30 mmHg

Tier Therapies •  Monitoring SjO2, AVDO2, and/orCBF
High Dose
Recommended
Barbiturate therapy
Second Tier Therapy

*Threshold of 20-25 mmHg may be used. Other values may be substituted in individual
 Osmotherapy

Mannitol induces changes in blood rheology and

increases cardiac output, leading to improved CPP
and cerebral oxygenation.
Improvements in cerebral oxygenation induce
cerebral artery vasoconstriction and subsequent
reduction in cerebral blood volume and ICP.
Mild dehydration after osmotherapy is desirable
and may improve cerebral edema.
Also it decreases CSF production by up to 50%,
lead to prolonged ICP decrease.
 Mannitol

Guideline
Mannitol is effective for control of raised ICP after
severe head injury.

Option
Effective doses range from 0.25 - 1.0 gm/kg
body weight.
Mannitol has several limitations;
• Hyperosmolality is a common problem, and a serum
osmolarity >320 mOsmol/L is associated with
adverse renal and central nervous system effects.
• Accumulation of mannitol in cerebral tissue may
lead to a rebound phenomenon and increased ICP.
• The indications for the use of mannitol prior to ICP
monitoring are signs of transtentorial herniation or
progressive neurological deterioration not
attributable to systemic pathology.
 The most promising solution investigated as
possible substitute for mannitol; is hypertonic
saline (HTS).
Serum Na is maintained between 145 and 155
mmol/L in all patients with TBI.
To start osmotherapy,250-mL bolus of 3% HTS is
administered through a central venous cannula.
This dose is repeated until ICP is controlled or a
Na level of 155 mmol/L is achieved.
The serum Na is maintained at this level until ICP
has stabilized and then gradually allowed to
normalize.
The permeability of the BBB to sodium is low.HTS produces an osmotic
gradient between the intravascular and intracellular compartments, leading
to shrinkage of brain tissue (where BBB is intact) and therefore reducing
ICP.
The selectivity of the BBB to NaCl is more than that of mannitol making it
potentially a more effective osmotic drug.
HTS augments volume resuscitation and increases circulating BV, MAP,
and CPP.
HTS restores the neuronal membrane potential, maintains BBB integrity,
and modulates the inflammatory response by reducing adhesion of
leukocytes to endothelium.
If ICP control is still problematic after 3–4 days of
HTS therapy, boluses of furosemide are
administered in an effort to mobilize tissue Na.

Serum sodium and potassium concentrations are

monitored four hourly on a blood gas analyzer.
 Analgesia and Sedation

Morphine or fentanyl can be used for analgesia but with

caution for their respiratory depression in case patient is
spontaneously breathing.
Remifentanyl can be used in ventilated patients.

Propofol is sedative of choice especially in first 48 hours. It

causes cerebral metabolic suppression and has
neuroprotective effect. Using propofol in doses more than
5mg/Kg and for longer than 48hrs;
Midazolam should replace propofol for sedation. (for fear of
propofol infusion syndrome).
 Barbiturates

Guideline
High-dose barbiturate therapy may be considered
in hemodynamically stable salvagable severe head
injury patients with intracranial hypertension
refractory to maximal medical and surgical ICP
lowering therapy.
 Barbiturate Coma

High-dose barbiturates are used to control intracranial

hypertension in selected patients. ICP is decreased due to decrease
in CBV due to vasoconstriction caused by increase in
cerebrovascular resistance.
Indications:
1. Potentially survivable head injury
2. No surgically treatable lesion accounting for intracranial hypertension
(except when used for preparation for surgery)
3. Other conventional therapies of controlling ICP have failed (posture,
hyperventilation, osmotic and tubular diuretics, corticosteroids)
4. ICP > 20 to 25 mmHg for more than 20 min, or >40 mmHg at any time
5. Unilateral cerebral hemispheric edema with significant (>.7 mm) shift of
midline structures shown on CT
6. A low Glasgow Coma score

Takeko Toyama, MD Assistant Professor of Anesthesiology University of Miami, Miami, FL

Goals
1. Maintenance ICP < 20 mmHG
2. Therapeutic EEG response: burst suppression or
cortical electrical silence (with preservation of
SSEP and BAEF)
Benefits:
1. Decrease in cerebral metabolic rate (CMRO2), caused by decrease in
synaptic transmission, presumably by affecting GABA transmission
2. Decrease in cerebral blood volume and ICP, due to increase in
cerebrovascular resistance, due vasoconstriction -Both CMRO2 and CBF
are decreased in a dose dependent fashion: About 50% decrease at a dose
3.
sufficient
Promote or to induce
produce isoelectric EEG
hypothermia
4. Increase in IC glucose, glucagon, and phosphocreatine energy store
5. Decrease in nitrogen excretion following acute head injury
6. Shunt blood from regions of normal perfusion to those of reduced CBF
due to vasoconstriction
7. Anticonvulsant prophylaxis
8. Stabilization of lysosomal membranes
9. Decrease in excitatory neurotransmitters and IC calcium
10. Free radical scavenging ( thiopental only)
Risks:
1. Direct myocardial depressant
2. Increase in venous capacitance, due to central and
peripheral sympatholytic action
3. Impaired gastrointestinal motility Increased
hepatic microsomal activity
4. Direct CNS depressant, resulting in unreliable
neurological examination
5. Possible allergic reaction Impaired lymphocyte
immune response and function
Dosing Regimens
Pentobarbital:
High dose:
Loading:30-40 mg/Kg over 4 hours (~2500mg/70Kg)
Maintenance: 1.8-3.3mg/Kg/hr (~175mg/70Kg)
Mid-level dose:
Loading: 10mg/Kg over 30min, 20-25mg/Kg over 4hr
maintenance: 5mg/Kg/hr for 3hrs,then 2-2.5mg/Kg/ with 5mg/Kg
bolus prn if serum level < 3mg/dl
Low dose:
Loading: 3-6mg/Kg over 30min
Maintenance: .3- 3mg/Kg/hr
Therapeutic serum level: 2.5-4 mg/dl ( 6 mg/dl may be needed )

Thiopental:
Loading:3mg/Kg bolus, followed by 10-20mg/Kg over 1 hr
Maintenance: 3-5 mg/Kg/hr
Therapeutic serum level: 6-8.5 mg/dl
Weaning: dosage is halved q 12 hr.
Monitoring
Cardiovascular
1. A-line: arterial BP, blood gases
2. PA catheter: CO, CI, SV, SVR, PVR, right heart filling pres., PCWP
3. Bladder catheter: urine output
Cerebrovascular and neurophysiological
1. ICP: maintain < 25 mmHg, preferably less
2. CPP: maintain > 70 mmHg
3. EEG: burst suppression, or cortical electrical silence optional
4. Brain temperature
5. Jugular bulb O2 monitor/ oxymeter catheter
6. Somatosensory or brainstem auditory evoked potentials (SSEP, BAEF)
Other monitoring
1. Core body temperature: NP, TM, E: 32 to 35 degrees C is acceptable
2. Serum barbiturate levels
3. nasogastric catheter: pH and output
4. intake and output
Therapy may be required for 7-14 days or longer, may be weaned after 3-6
days
1. Therapeutic end points

2. Success:
1. ICP < 20 mmHg for at least 48 hours, at a minimum
2. Resolution of intracranial mass effects or midline shift, preferably
3. ICP must remain controlled with conventional therapies
3. Failure:
1. Diagnosed brain death
2. Uncontrollable ICP despite adequate serum levels, EEG burst-
3. Suppression, or electrical silence
4. Intolerable side effects;
1. Hypotention not responsive to cardiac inotropes, peripheral vaso- pressors, or
intravenous fluid therapy (cardiac isotopes: dopamine, dobutamine,
epinephrine) (peripheral vasopressors: ephedrine, phenylephrine)
2. (IV fluids: packed RBCs, albumine, hetastarch, LR)
3. Progressive pulmonary dysfunction
4. Sepsis
 Steroids

Standard
The use of steroids is not recommended for
improving outcome or reducing intracranial pressure
in patients with severe head injury.
Multiple prospective, randomized studies have
demonstrated no benefit in lowering ICP or
improvement in patient outcome through the use of
high-dose corticosteroids in acute TBI .
The use of methylprednisolone in patients with
moderate to severe TBI has been demonstrated to
increase mortality and is contraindicated.
 Mechanical ventilation

In TBI patients, hypoxia, hypercarbia /

hypocarbia should be prevented.
PaO2 should be above 100mmHg and SpO2 above
95%.
Mechanical ventilation should be started at GCS 8.
PaCO2 in first 24hrs should be 34-38mmHg and
mild hyperventilation can be started for PaCO2 to be
32-35mmHg in case of increased ICP.
Monitor end tidal CO2 and perform blood gases 15-
20 min. after any change in ventilatory parameters.
 Hyperventilation

Standard
In the absence of increased intracranial pressure (ICP), chronic
prolonged hyperventilation therapy (PaCO 2 of 25 mm Hg or less)
should be avoided after severe traumatic brain injury (TBI).
Guideline
The use of prophylactic hyperventilation (PaCO 2 < 35 mm Hg) therapy
during the first 24 hours after severe TBI should be avoided because it
can compromise cerebral perfusion during a time when cerebral blood
flow (CBF) is reduced.
Option
Hyperventilation therapy may be necessary for brief periods when there
is acute neurologic deterioration, or for longer periods if there is
intracranial hypertension refractory to sedation, paralysis,
cerebrospinal fluid (CSF) drainage, and osmotic diuretics.
Hypercapnea is a potent cerebral vasodilator and
should be avoided in patients with cerebral edema
and elevated ICP.
Hyperventilation reduces ICP by causing cerebral
vasoconstriction and reducing cerebral blood flow.
Aggressive hyperventilation has been used for years in
the treatment of elevated ICP, but has been
demonstrated to have a deleterious outcome
Hyperventilation should be avoided in the first 24
hours post-injury when cerebral blood flow is often
critically reduced.
Hyperventilation may have a role as a temporizing
measure in the acute reduction of elevated ICP.
When hyperventilation is used for more than a brief
period of time, monitoring of cerebral oxygenation
using either jugular venous bulb oximetry (SjvO2) or
brain tissue oxygen tension (PbrO2) should be
considered.
 Neuromuscular blockade

May be considersd to facilitate endotracheal

intubation.

In cases of difficult ventilation inspite of adequate

sedation/analgesia.

Use of neuromuscular blockade may mask seizure

activity, increase risk of pneumonia and cause
critical illness neuropathy.
 Patient positioning

Patient head should be in neutral position with head

of bed elevated 15-30 degree.

Neck collar should be applied whenever there is

doubt of cervical spine injury.
 Surgical Intervention

Whenever decided by neurosurgeon to decrease

intracranial hypertension.

Surgery can be performed on mass lesions or to

eleminate objects that penetrated the brain.

Mass lesions are like contusions or haematomas

causing significant shift of intracranial structures.
 Maintenance of haematological
parameters
Monitor HCT or haemoglobin level as CBF is
influenced by blood viscosity which increases by
increase in HCT.
CBF is reduced by HCT levels above 50% and
increased by HCT levels below 30%.
HTC of 30-34% is suggested to be best for optimal
oxygen delivery to brain tissue.
 Antiseizure Prophylaxis

Standard
Prophylactic use of phenytoin, carbamazepine,
phenobarbital or valproate is not recommended
for preventing late post-traumatic seizures.
 Control of seizures

Seizure activity in TBI patients may cause secondary

brain damage as a result of increased metabolic
demands, raised ICP and excess neurotransmitter
release.
Benzodiazepines should be started together with
phenytoin .
Adequate sedation with propofol reduces seizure
activity and raises seizure threshold.
 Fever
Elevated body temperature increases the patient’s inflammatory
response by elevating levels of pro-inflammatory cytokines
and neutrophils. This can increase sympathetic tone, resting
energy expenditure, oxygen consumption, heart rate, and
minute
While feverventilation.
occurs in 30-45% of the non-neurologically injured,
it may be seen in up to 70% of those with TBI. In these
patients, an infectious etiology is present less than 50% of the
time, with the remainder being classified as “central fever.”
Central fever is believed to be due to direct damage to the
thermoregulatory centers of the brain, which are found in the
preoptic nucleus of the hypothalamus and focal centers of the
pons. Severe damage to these centers can also result in
profound hypothermia, which can result in coagulopathy,
cardiac arrhythmias, or depressed immune function.
Early fever following TBI has been associated with
lower GCS, presence of diffuse axonal injury,
cerebral edema, hypotension, hypoglycemia, and
leukocytosis .
Fever within the first week is associated with increased
intracranial pressure, neurologic impairment, and
prolonged ICU stay
Hypothermia is also associated with worse outcomes
in TBI.
Aggressive efforts to control temperature in the TBI
patient should be implemented including early
intravenous and enteral antipyretic medications,
control of room temperature, and cooling blankets or
pads.
Due to the deleterious effect of temperature on brain
parenchyma, therapy should be initiated when
patient temperature exceeds 37˚ Celsius rather than
waiting until the traditional definition of fever has
been reached.
 Therapeutic Hypothermia

Therapeutic hypothermia has been demonstrated to

improve neurologic outcome following witnessed
arrest from ventricular fibrillation or pulseless
ventricular tachycardia.
Data supporting its use following TBI has been less
convincing.
While normothermia has few potential side effects,
the potential complications of therapeutic
hypothermia include hypotension, arrhythmia,
electrolyte disorders, impaired coagulation,
shivering, hyperglycemia, and increased risk of
infection.
Therapeutic hypothermia may have a role in the
treatment of patients with severe TBI and refractory
ICP, but should only be used after consultation
between the attending intensivist and neurosurgeon.
When therapeutic hypothermia has been initiated,
therapy should be continued until ICP < 20 mmHg
for 48 hrs at which time patients may be rewarmed
at a rate not to exceed 0.1˚ Celsius per hour with
close monitoring for the development of rebound
intracranial hypertension.
 Shivering management
When body temperature is lowered, the physiologic response is to
prevent further heat loss through vasoconstriction. When
vasoconstriction is no longer effective, shivering occurs to
counterbalance heat loss.
In the context of induced hypothermia, shivering is undesirable
because it causes patient discomfort, increases body temperature,
increases metabolic / oxygen demand, and increases intraocular
and intracranial pressures.
A step-wise approach to the prevention of shivering appears
appropriate. Pharmacologic options for the control of shivering
include: meperidine, morphine, fentanyl, propofol, magnesium,
benzodiazepines, and neuromuscular blockers .
It is important to consider that data on pharmacologic interventions
for shivering control are based upon experience with either health
volunteers or in the postoperative setting (20-23). Therefore, the
effect of repetitive dosing and prolonged use of these agents in
therapeutic hypothermia is lacking (i.e. CNS toxicity associated with
merperidine).
 Targeted Temperature Management

With the deleterious effects of fever and hypothermia established for TBI
patients, many modalities of achieving either normothermia or therapeutic
hypothermia have been described .
Conventional cooling methods include skin exposure, ice, cold packs, infused
cold fluid, peritoneal lavage, and antipyretics. There are also many
commercially available cooling devices available. The Blanketrol
(Cincinnati Subzero, Cincinnati, OH) is a water-circulating blanket system
that utilizes two large cooling blankets, one beneath and one on top of the
Thepatient,
Arctic to
Sunmaintain the desired
(Medivance, patient temperature.
Jugenheim, Germany) circulates water through
gel pads that are applied to the patient’s back, abdomen, and thighs,
automatically controlled by a rectal thermometer. Several intravascular
cooling systems are also commercially available. These systems infuse cold
fluids via a closed-loop central venous catheter to maintain the desired
In body temperature.
a prospective study of ICU patients, Hoedemakers et al found superior
temperature control using water-circulating blankets, gel-pads, and
intravascular cooling as compared to conventional cooling techniques and
air-circulating blankets /
 Nutrition

Guideline
Replacement of 140% of Resting Metabolic
Expenditure in non-paralyzed patients and
100% Resting Metabolic Expenditure in
paralyzed patients using enteral or parenteral
formulas containing at least 15% of calories as
protein by the seventh day after injury.
Prospective trial in 38 patients randomly assigned to
receive total parenteral nutrition (TPN) or standard
enteral nutrition (SEN).
The TPN group got full nutritional support by 7 days
whereas the SEN group did not. There were
significantly more deaths in the group that did not
receive full caloric replacement by the 7th day after
injury.

J. Neurosurg 58:907-912, 1983

 Monitoring renal function

Urine output should be 0.5-1ml/Kg/min.

Diabetes insipidus should be suspected if urine
output is more than 250ml/hr, for more than 3hrs.
and specific gravity less than 1005,confirmed by
serum and urine osmolalities.
If confirmed , start desmopressin.
 TIERS OF THERAPY

TIER ZERO
TIER ONE
TIER TWO
TIER THREE
 TIER ZERO

The following interventions should be

implemented in all patients with TBI:
Maintain mean arterial pressure (MAP) > 80
mmHg if GCS < 8; otherwise target MAP > 70
mmHg
Administer supplemental oxygen to maintain SpO2
> 92%
Elevate head of bed to 30 degrees
Maintain head in neutral position to avoid jugular
vein constriction
Correct hyponatremia (serum Na+ < 140 mEq/L)
with isotonic intravenous fluids (no dextrose)
 Correct coagulopathy with Prothrombin Complex
Concentrate (PCC) in life-threatening bleeds
FEIBA NF 1000 units IV push over 5 minutes
Transfuse platelets in patients with known history of
antiplatelet agent use
Avoid hyperthermia (temperature > 37˚Celsius)
Acetaminophen 650 mg PO/PT q 4 hrs
Avoid hyperglycemia (serum glucose > 180 mg/dL)
Ensure early appropriate nutritional support
Prevent deep venous thrombosis (DVT)
Prevent gastrointestinal stress ulceration
Prevent skin breakdown / decubitus ulcer formation
through appropriate bed surface
 TIER ONE
The following interventions should be added in all patients with
Glasgow Coma Score (GCS) < 8:
Ensure all physiologic goals from Tier Zero are met
Airway / Breathing
Intubate patient if GCS < 8 and as needed to protect the airway
Maintain PaCO2 35-40 mmHg
Maintain PaO2 80-120 mmHg
Systemic and Cerebral Perfusion
Insert an arterial line (leveled at the phlebostatic axis)
Insert a central venous catheter for central venous pressure (CVP) monitoring
Maintain euvolemia (fluid balance positive by 500-1000 mL in first 24 hrs,
CVP > 8 mmHg)
Maintain MAP > 80 mmHg if ICP is unavailable
Maintain cerebral perfusion pressure (CPP=MAP-ICP) > 60 mmHg if ICP is
available
If CPP < 60 mmHg, notify intensivist and:
If CVP < 8 mmHg, give normal saline 500-1000 mL bolus
If CVP > 8 mmHg, start norepinephrine 0-0.5 mcg/kg/min IV infusion to
maintain CPP
Consider ICP monitoring
Indications
Salvageable patients with severe TBI (GCS 3-8 after resuscitation) and an abnormal CT
scan (hemorrhage, contusions, swelling, herniation or compressed basal cisterns)
Patients with severe TBI and normal CT scan if two of the following are noted at
admission: age > 40 yrs, unilateral or bilateral posturing, systolic BP < 90 mmHg
Patients with TBI who will not be examinable for a prolonged period of time
Management
Maintain ICP < 20 mmHg
Consider Osmolar Therapy (see below)
Consider short-term hyperventilation (PaCO2 30-34 mmHg) to acutely reduce ICP
Verify correct ICP waveform on extraventricular drain (EVD); notify neurosurgery if ICP
waveform is incorrect or there is no CSF drainage
Level EVD at the external auditory meatus
Close EVD and level at 0 mmHg upon insertion to monitor ICP
If ICP > 20 mmHg for 10 minutes, open EVD at 0 mmHg for 15 minutes
If EVD is opened more than 3 times within 90 minutes, leave EVD open at 0 mmHg
continuously and notify neurosurgery
Osmolar Therapy
First line therapy
3% normal saline IV bolus 100-250 mL q 2 hrs prn ICP > 20
mmHg for > 10 minutes
Alternate therapy
Mannitol 0.25-1.0 gm/kg IV q 6 hrs prn ICP > 20 mmHg
Measure serum osmolality and electrolytes q 6 hrs
Notify intensivist if serum Na changes by > 3 mEq/L from
previous measurement
Hold hypertonic saline therapy for serum Na > 160 mEq/L
Hold mannitol therapy for serum osmolality > 320 mOsm
Protect the Brain
Initiate continuous EEG monitoring to rule non-convulsive status epilepticus
Provide judicious analgesia and sedation to control pain and agitation
Fentanyl 25-150 mcg/hr IV infusion
Propofol 10-50 mcg/kg/hr IV infusion for Richmond Agitation Sedation Score (RASS) >
-2
Exclude seizure activity
Keppra 500 mg IV BID for first 7 days (discontinue after 7 days if no seizure activity)
Avoid:
Hypotension (MAP < 70 mmHg)
Hypoxemia (SpO2 < 92%)
Hypercarbia (PaCO2 > 45 mmHg)
Hyponatremia (serum Na+ < 140 mEq/L)
Hyperglycemia (glucose > 180 mg/dL)
Hypovolemia
Fever (maintain temperature at 36-37˚Celsius)
Anemia (maintain hemoglobin > 9 gm during the patient’s critical illness)
 TIER TWO

The following interventions should be considered if ICP is

persistently > 20 mmHg for more than 60 minutes after
discussion with neurosurgery and intensivist attendings:
Ensure all physiologic goals from Tier One are met
Consider head CT scan to rule out space-occupying lesion
Consider continuous EEG monitoring to rule non-convulsive status
epilepticus
Paralysis
Start rocuronium (50 mg/kg loading dose, then 8 mcg/kg/hr);
adjust dose according to Train of Four
Mild Hypothermia
Induce hypothermia to 35˚ Celsius using the Arctic Sun™ cooling
pads
Mild Hyperventilation
Begin mild hyperventilation with goal PaCO2 30-34 mmHg
 TIER THREE

The following interventions should be considered if ICP

remains > 20 mmHg despite all Tier Two goals being met:
Ensure that medical therapy with hypertonic saline is maximized
Consider revised ICP threshold of 25 mmHg with strict adherence
to CPP goals
Initiate continuous EEG (if not already present)
Consider 23.4% hypertonic saline 30 mL IVP for refractory ICP
Surgical Decompression
Consider decompressive craniectomy in consultation with
neurosurgery team
Hypothermia
Consider hypothermia to 34˚ Celsius using the Arctic Sun cooling
blanket
Once ICP < 20 mmHg for 48 hrs, rewarm at rate no greater than
0.1˚ Celsius/hr
 Barbiturate Coma
If not a surgical candidate, and refractory to all above
interventions, consider pentobarbital coma
Pentobarbital 10 mg/kg IV over 10 minutes, then 5
mg/kg IV q 1 hr x 3, then 1 mg/kg/hr IV infusion
Titrate pentobarbital to the minimal dose required to
achieve EEG burst suppression
Discontinue all other sedative agents and paralytics
Strongly consider invasive hemodynamic monitoring
(such as pulmonary artery catheter) due to the negative
inotropic effects of pentobarbital
Once ICP < 20 mmHg for 48 hrs, taper pentobarbital
dose over the next 48-72 hrs
 Figure 1. Suggested algorithm for cerebral resuscitation after traumatic brain injury, adapted from
the Brain Trauma Foundation and the European Brain Injury Consortium Guidelines and modified to
replace mannitol with hypertonic saline for osmotherapy.

White H et al. Anesth Analg 2006;102:1836-1846