Brain Injuries

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Neurocritical care focuses on critically ill patients with primary
or secondary neurological problems. Initially neurocritical care
was developed to manage postoperative neurosurgical patients;
it then expanded to the management of patients with traumatic
brain injury (TBI), intracranial hemorrhage and complications of
subarachnoid hemorrhage, including vasospasm, elevated
intracranial pressure (ICP) and the cardiopulmonary
complications of brain injury (Bamford 1992). The striking
improvements noted in many studies suggest that high-quality
neurocritical care with the delivery of targeted therapeutic
interventions does have an impact, not only on survival, but
importantly also on the quality of survival.
Types of Brain Injuries
Primary brain injuries
Ischemic brain injury: either global, which includes cardiac
arrest or anoxia, or regional ischemic brain injury, which
includes vasospasm, compression of blood vessels or stroke.
Stroke can be classified into ischemic and hemorrhagic strokes.
Ischemic stroke accounts for 80% of all strokes and can be
further classified into thrombotic or embolic stroke; ischemic

thrombotic stroke accounts for 77% while ischemic embolic
stroke constitutes the remainder.
Hemorrhagic strokes constitute 10-20% of all strokes, and can
be further classified into two types, the intracerebral
hemorrhage that constitutes up to 75% and the subarachnoid
hemorrhage that makes up the other 25%.
Acute ischemic stroke is the third leading cause of death in
industrialized countries and the most frequent cause of
permanent disability in adults worldwide, so understanding the
pathogenesis of ischemic stroke is mandatory. Despite great
strides in understanding the pathophysiology of cerebral
ischemia, therapeutic options remain limited. Only recombinant
tissue plasminogen activator (rTPA) for thrombolysis is
currently approved for use in the management of acute ischemic
stroke.
However, its use is limited by its short therapeutic window (3-
4.5 hours), complications from the risk of hemorrhage, and the
potential damage from reperfusion injury. Effective stroke
management requires recanalization of the occluded blood
vessels. However, reperfusion can cause neurovascular injury,
leading to cerebral edema, brain hemorrhage, and neuronal
death by apoptosis or necrosis (Hajjar 2011).
Central nervous system (CNS) infections: Acute onset fever
with altered mental status is a problem commonly encountered
by the physician in the emergency setting. “Acute febrile
encephalopathy” is a commonly used term for description of the
altered mental status that either accompanies or follows a short
febrile illness. CNS infections are the most common cause of
nontraumatic disturbed consciousness. The etiologic agents may
be viruses, bacteria, or parasites. Central nervous system
infections are classified into categories beginning with those in
immunocompetent hosts followed by infection with the human
immunodeficiency virus (HIV) and its opportunistic infections.
The viruses responsible for most cases of acute encephalitis in
immunocompetent hosts are herpes viruses, arboviruses, and
enteroviruses. Neurotropic herpes viruses that cause

encephalitis predominantly in immunocompetent hosts include
herpes simplex virus 1 (HSV-1) and 2 (HSV-2), human herpes
virus 6 (HHV-6) and 7 (HHV-7), and Epstein-Barr virus (EBV).
Cytomegalovirus (CMV) and varicella-zoster virus (VZV) may in
some situations cause encephalitis in immunocompetent
patients, but more commonly they produce an opportunistic
infection in immunocompromised individuals, such as those
with HIV infection, organ transplant recipients, or other patients
using immunosuppressive drugs. HSV-1 is the most common
cause of severe sporadic viral encephalitis in the United States;
diagnosis has been become more familiar due to the availability
of cerebrospinal fluid (CSF) polymerase chain reaction (PCR)
analysis techniques that allow for rapid, specific, and sensitive
diagnoses. The use of CSF PCR instead of brain biopsy as the
diagnostic standard for HSV encephalitis has expanded
awareness of mild or atypical cases of HSV encephalitis. Adult
encephalitis is caused by 2 viral serotypes, HSV-1 and HSV-2.
Patients with greater than 100 DNA copies/μL HSV in CSF are
more likely than those with fewer copies to have a reduced level
of consciousness, more significant abnormal findings on
neuroimaging, a longer duration of illness, higher mortality, and
more sequelae (Domingues 1997). EBV is almost never cultured
from CSF during infection, and serological testing is
inconclusive, so CSF PCR diagnosis is mandatory.
Semiquantitative PCR analysis of EBV DNA suggests that copy
numbers are significantly higher in patients with active EBV
infection. HHV-6 and -7 can cause exanthema subitum, and
appear to be associated with febrile convulsions, even in the
absence of signs of exanthema subitum. Almost all children
(>90%) with exanthema subitum have HHV-6 or HHV-7 DNA in
CSF. Inflammatory primary brain damage like meningitis and
encephalitis come from pyogenic infections that reach the
intracranial structures in one of two ways - either by
hematogenous spread (infected thrombi or emboli of bacteria) or
by extension from cranial structures (ears, paranasal sinuses,
osteomyelitic foci in the skull, penetrating cranial injuries or

congenital sinus tracts). In a good number of cases, infection is
iatrogenic, being introduced in the course of cerebral or spinal
surgery, during the placement of a ventriculoperitoneal shunt or
rarely through a lumbar puncture needle. Nowadays, nosocomial
infections are as frequent as the non-hospital acquired variety.
The reason for altered sensorium in meningitis is postulated to
be the spillage of inflammatory cells to the adjacent brain
parenchyma and the resultant brain edema (Levin 1998).
Compressive brain injury: e.g., tumors and cerebral brain
edema are considered as important causes for impairment of the
level of consciousness. During tumor growth, cerebral tissues
adjacent to the tumor and nearby venules are compressed,
which results in elevation of capillary pressure, particularly in
the cerebral white matter, and there is a change in cerebral
blood flow and consequently intracranial pressure. At that stage
the tumor begins to displace tissue, which eventually leads to
displacement of tissue at a distance from the tumor, resulting in
false localizing signs such as transtentorial herniations,
paradoxical corticospinal signs of Kernohan and Woltman, third
and sixth nerve palsies and secondary hydrocephalus, originally
described in tumor patients.
Secondary brain injuries
Secondary brain injuries include renal coma, hepatic coma, salt
and water imbalance, disturbance of glucose metabolism, other
endocrinal causes of coma, disturbances of calcium and
magnesium metabolism, drug intoxication and other material
intoxication, not only drug toxicity, hypertensive and metabolic
encephalopathies, sleep apnea syndromes and other ventilator
disturbances. Mechanisms of secondary brain injury include
hypoxia, hypoperfusion, reperfusion injury with free radical
formations, release of excitatory amino acids and harmful
mediators from injured cells, electrolyte and acid base changes
from systemic or regional ischemia (Semplicini 2003).
The primary goal in managing neurologically compromised
patients includes (Stasiukyniene 2009) stabilizing the brain

through the maintenance of oxygen delivery via the following
parameters:
1. Assuring systemic oxygen transport and adequate
oxygenation, maintaining hemoglobin level (at
approximately 10 g/dl or more) and cardiac output.
2. Assuring optimal mean arterial pressure (MAP). Many
insults are associated with hypertension, which may be a
physiologic compensation, so excessive lowering of blood
pressure may induce secondary ischemia. In general,
systolic pressure should be treated when more than 200
mmHg or MAP when more than 125 mmHg. Cautious
reduction in mean arterial pressure by only 25% is
recommended (Adams 2007).
3. Avoiding prophylactic or routine hyperventilation - a
decrease in extracellular brain pH may produce
vasoconstriction in responsive vessels and reduce CBF to
already ischemic zones. This applies to patients with head
trauma in whom routine hyperventilation is no longer
considered desirable; brief hyperventilation may be
lifesaving in the patient with herniation, pending the
institution of other methods to lower elevated ICP.
4. Assuring euvolemia. Hypervolemia may also be helpful
when vasoconstriction is suspected, as in the setting of
subarachnoid hemorrhage.
5. Consideration should be given to administering
intravenous lidocaine 1.5 mg/kg or intravenous thiopental
(5 mg/kg) to blunt the rise in ICP associated with
intubation.
6. Nimodipine should be instituted immediately in patients
with SAH and is advocated by some in patients with
subarachnoid bleeding after head trauma. Nimodipine
probably improves outcome by decreasing calciummediated
neuronal toxicity.
7. Using normal saline as the primary maintenance fluid;
dextrose administration is usually avoided unless the

patient is hypoglycemic; hypotonic solutions should also be
avoided.
8. Assessing and treating coagulation defects.
9. Sedation and/or neuromuscular blockade after intubation
may be required to control harmful agitation.
10. If seizure occurrs, it should be aggressively treated.
11. Titration of the ICP and cerebral perfusion pressure.
Management of Special Issues
Traumatic brain injury
Outcome after traumatic brain injury depends upon the initial
severity of the injury, age, the extent of any subsequent
complications, and how these are managed. Much of the early
management of traumatic brain injury falls upon emergency
room staff, primary care and ambulance services prior to
hospital admission. Most patients who attend hospital after a
traumatic brain injury do not develop life-threatening
complications in the acute stage. However, in a small but
important subgroup, the outcome is made worse by failure to
detect promptly and deal adequately with complications.
General rules:
1. A traumatic brain injury should be discussed with
neurosurgery when
a. a CT scan in a general hospital shows a recent
intracranial lesion
b. a patient fulfills the criteria for CT scanning but this
cannot be done within an appropriate period
c. whatever the result of the CT scan, the patient has
clinical features that suggest that specialist
neurological assessment, monitoring, or management
are appropriate. Reasons include:
i. Persistent coma (GCS <9, no eye opening) after
initial resuscitation
ii. Confusion persisting for more than 4 hours

iii. Deterioration in level of consciousness after
admission (a sustained decrease of one point in the
motor or verbal GCS subscores, or 2 points on the
eye opening subscale of the GCS)
iv. Persistent focal neurological signs
v. A seizure without full recovery
vi. Compound depressed fracture
vii. Suspected or definite penetrating injury
viii. A CSF leak or other sign of base of skull fracture
2. Keep sodium >140 mmol/L. A fall in serum sodium produces
an osmotic gradient across the blood–brain barrier, and
aggravates cerebral edema.
3. Avoid hyperglycemia (treat blood glucose >11 mmol/L).
Hyperglycemia increases cerebral lactic acidosis, which
may aggravate ischemic brain injury.
4. Feed via an orogastric tube. Gastric motility agents can be
given as required.
5. Use TED stockings; avoid low-dose heparin.
6. Apply 15–30° head-up tilt with head kept in neutral
position; this may improve CPP.
7. No parenteral hypotonic fluid must be given.
Acute stroke
The World Stroke Organization declared a public health
emergency on World Stroke Day (WSO 2010). There are 15
million people who have a stroke each year. According to the
World Health Organization, stroke is the second leading cause of
death for people above the age of 60, and the fifth leading cause
in people aged 15 to 59. Stroke also happens to children,
including newborns. Each year, nearly six million people die
from stroke. In fact, stroke is responsible for more deaths
annually than those attributed to AIDS, tuberculosis and malaria
put together. Stroke is also the leading cause of long-term
disability irrespective of age, gender, ethnicity or country.
Yet for many healthcare staff it remains an area of therapeutic
nihilism and thus uninteresting and neglected (WSO 2010). This

negative perception is shared by the general public, who often
has a poor understanding of the early symptoms and significance
of a stroke.
Yet within the last few years there have been many important
developments in the approach to awareness and caring for
stroke patients, for both the acute management and secondary
prevention. Clinical research and interest in stroke has increased
greatly in the last few years. Each minute of brain ischemia
causes the destruction of 1.9 million neurons, 14 billion
synapses, and 7.5 miles of myelinated nerves (Hand 2006).
Ischemic stroke is characterized by one or more focal
neurological deficits corresponding to the ischemic brain
regions. It requires an immediate decision regarding
thrombolytic therapy (tissue plasminogen activator, TPA, in the
dosage of 0.9 mg/kg, 10% as a bolus over 1 minute and infuse the
remaining 90% over the next hour).
Wise control of hypertension is essential, control of
hyperglycemia and fever is protective against more destruction
of neurons (Mistri 2006).
Status epilepticus (SE)
Status epilepticus is defined as more than 30 minutes of
continuous seizure activity or recurrent seizure activity without
an intervening period of consciousness (Manno 2003).
In one survey, only 10% of patients who develop seizures in a
medical ICU will develop SE. The most common causes of SE are
noncompliance with or withdrawal of antiepileptic medications,
cerebrovascular disease and alcohol withdrawal.
The hypersynchronous neuronal discharge that characterizes a
seizure is mediated by an imbalance between excitation and
inhibition. The adverse effects of generalized seizures include
hypertension, lactic acidosis, hyperthermia, respiratory
compromise, pulmonary aspiration or edema, rhabdomyolysis,
self-injury and irreversible neurological damage (Bassin 2002).
The most common and potentially dangerous forms of status
epilepticus are generalized convulsive status epilepticus, non

convulsive generalized status epilepticus, refractory status
epilepticus and myoclonic status epilepticus. Also, seizures that
persist for longer than 5-10 minutes should be treated urgently
because of the risk of permanent neurological injury and
because seizures become refractory to therapy the longer they
persist (Stasiukyniene 2009).
General measures for management are shown in Table 4.1.
Intravenous drug therapy for convulsive seizures in the ICU are
as follows:
1. Lorazepam: 0.10 mg/kg up to 2 mg/min or diazepam 0.15
mg/kg; if seizure continues, give
2. Fosphenytoin: 20 mg/kg up to 150 mg/min or phenytoin 20
mg/kg up to 50 mg/min; if seizure continues, one of the
following medications may be used but these require intubation
and mechanical ventilation:
– phenobarbital 20 mg/kg up to 50 mg/min
– propofol 3-5 mg/kg load then 1-15 mg/kg/hr
– midazolam 0.2 mg/kg load then 0.05-2 mg/kg/hr
– pentobarbital 5-15 mg/kg load, then 0.5-10 mg/kg/hr
Neuromuscular emergencies
Neuromuscular emergencies are composed of a group of severe
life-threatening neuromuscular diseases such as myasthenic
crises, cholinergic crises, critical illness myopathy and critical
illness polyneuropathy.
Respiratory paralysis occurs in a small percentage of patients
with acute neuromuscular disease and accounts for less than 1%
of admissions to general intensive care units. Its development
may be insidious so that patients with acute neuromuscular
disease should have their vital capacity monitored. Orotracheal
intubation and ventilatory support should be instituted
prophylactically when vital capacity is falling towards 15 ml/kg.
Earlier intervention is necessary in the presence of bulbar palsy.

Table 4.1 – General measures for management of Status Epilepticus*
1 (0–10 minutes)
Assess cardiorespiratory function
Secure airway and resuscitate
Administer oxygen
2 (0–60 minutes)
Institute regular monitoring
Emergency antiepileptic drug therapy
Set up intravenous lines
Emergency investigations
Administer glucose (50 ml of 50% solution) and/or intravenous
thiamine (250 mg) as high potency intravenous Pabrinex where appropriate
Treat acidosis if severe
3 (0–60/90 minutes)
Establish etiology
Identify and treat medical complications
Pressor therapy where appropriate
4 (30–90 minutes)
Transfer to intensive care
Establish intensive care and EEG monitoring
Initiate seizure and EEG monitoring
Initiate intracranial pressure monitoring where appropriate
Initiate long term, maintenance, antiepileptic therapy
These four stages should be followed chronologically; the first and second
within 10 minutes, and stage 4 (transfer to intensive care unit) in most settings
within 60–90 minutes of presentation.
*Derived from Shorvon 1994
After assessment of these important conditions, and once the
respiratory consequences of progressive neuromuscular
weakness are established, the following requirements for
management of critical neuromuscular diseases in ICU should be
fulfilled:
1. Continuous monitoring of oxygen saturation to stay above
95%; pacemaker to be considered if heart rate variability is
abnormal.
2. Assessment of muscle strength through measurement of
vital capacity, hand grip strength (dynamometer), arm
abduction time, head lifting time, loudness of voice, ability
to swallow secretions and use of accessory muscles of
ventilation.

3. Management of inability to swallow through frequent
suction, head positioning to allow use of a nasogastric, an
orogastric or a Guedel tube.
4. Assessment of cardiac output, e.g., in myositis and
arrhythmias (autonomic fiber involvement in GBS),
heparinization for prevention of deep venous thrombosis,
care for decubital ulcers.
5. Indications for intubation and artificial ventilation in
neuromuscular critical cases: If oxygen saturation is below
90% (below 85% if more chronic), exhaustive respiratory
work, forced vital capacity falling below 15 ml/kg and
recurrent minor aspiration, avoid use of muscle relaxants.
If artificial ventilation is likely to be required for more than
approx. seven days, a tracheostomy should be created and
is more comfortable for the patient than continued
orotracheal intubation. Nutrition should be provided early
via a nasogastric tube. Strenuous efforts should be made to
reduce the incidence of nosocomial infection. Patients with
neuropathy should be monitored for autonomic
dysfunction causing cardiac arrhythmia or fluctuating
blood pressure. Deep vein thrombosis should be avoided by
regular passive limb movements and low-dose
subcutaneous heparin.
6. Use assisted ventilation with IMV mode with low PEEP of 3
cm H20 except in pneumonia, atelectasis and use as few
sedatives as possible to monitor neurologic findings
(Murray 2002). Critical illness polyneuropathy and
myopathy are considered conditions associated with
inflammatory injury to major organs involving peripheral
nerves and skeletal muscles, and may add considerable
value to the morbidity and mortality of the ICU stays.
7. If systolic pressure remains below 90 mmHg after adequate
volume replacement, begin dopamine infusion to maintain
systolic pressure above 90 mmHg; if dopamine is
inadequate maintain dopamine and start dobutamine
infusion. If the patient develops diabetes insipidus with

urine output exceeding 250 ml/hour for 2 hours, start a
vasopressin infusion at a dose of 0.5-1.0 U/hour for adults,
titrate infusion to maintain urine output at 100-200
ml/hour. Send tracheal aspirate, urine and blood for
routine and fungal culture (Shoemaker 2000).
Metabolic disturbances such as hypokalemia or
hypermagnesemia should always be looked for and corrected
first. In Guillain–Barré syndrome we recommend intravenous
immunoglobulin as being equally effective to plasma exchange,
safer, and more convenient. In myasthenia gravis we
recommend intravenous immunoglobulin followed by
thymectomy or, where thymectomy is inappropriate or has been
unsuccessful, intravenous immunoglobulin combined with
azathioprine and steroids. In polymyositis and dermatomyositis,
steroids are the mainstay of treatment but intravenous
immunoglobulin is also effective.
Management of subarachnoid hemorrhage
Subarachnoid hemorrhage (SAH) is a complex medical and
surgical event. Among its multiple etiologies, one of the most
common relates to bleeding from a cerebral aneurysm. The
optimal management of this life-threatening condition relies on
a systematic and organized approach leading to the correct
diagnosis and timely referral to a capable neurosurgeon. The
following is a brief summary of steps that should be initiated
when SAH is suspected, and the role of a medical neurocritical
care facility.
A CT scan should be obtained immediately after the diagnosis is
suspected. If the CT scan is positive, lumbar puncture is
unnecessary and even dangerous due to the risks of aneurismal
rebleeding or transtentorial brain herniation. If the CT scan is
negative, lumbar puncture may be helpful if the history of the
ictal headache is not typical of subarachnoid hemorrhage,
insidious in onset, or of migrainous character. If the patient

relates a history typical of SAH, a cerebral CT arteriogram should
be performed despite a negative CT scan. Up to 15% of CT scans
obtained within 48 hours of SAH will be negative.
Once the diagnosis is confirmed with a CT scan, a neurosurgeon
who can treat the patient should be contacted immediately.
Delays in transfer may prove fatal because of the potential for
aneurismal rebleeding prior to intervention. It is often best to
allow the interventionist or surgeon who will be caring for the
patient to arrange for the diagnostic arteriogram to be
performed at the institution where the patient will undergo
intervention or surgery to repair the aneurysm. Arteriography
performed by institutions infrequently treating SAH may be
technically inadequate and require repetition upon transfer to
the interventionist.
Blood pressure must be closely monitored and controlled
following SAH. Hypertension will increase the chance of
catastrophic rebleeding. Blood pressure control should be
initiated immediately upon diagnosis of SAH.
Medical preoperative management includes prophylactic
anticonvulsants, calcium channel blockade, corticosteroids, and
antihypertensives as needed. We do not initiate antifibrinolytic
therapy unless surgery is not considered within 48 hours of the
initial SAH.
Medications that can be initiated prior to transfer to
interventionist or neurosurgeon include:
– dexamethasone, 4 mg IV six hourly
– nimodipine, 60 mg orally four hourly
– phenytoin, 10 mg/kg IV load, then 100 mg orally/IV three
times daily
A frequent source of diagnostic difficulty for the
interventionist lies in the use of excessive amounts of narcotic
analgesics prior to transfer to the neurosurgical service.
Although pain control facilitates blood pressure control, the
ability to grade accurately the patient’s level of consciousness
has significant impact on the timing of intervention. Clinical

grading also, obscured by large doses of narcotic analgesics,
makes surgical planning more difficult.