TRAUMATIC BRAIN INJURY

Tara N. Hammond, DVM, DACVECC

Tufts Veterinary Emergency Treatment & Specialties

Traumatic Brain Injury

Epidemiology

Pathophysiology

Physical Exam

Diagnostics

Treatment/Prognosis

Current Literature

Epidemiology (humans) > 2 million head injuries/year

> 60,000 deaths from TBI yearly

80% minor, 10% moderate, 10% severe

  Accounts for ~50% of deaths from trauma

Financial burden: $100-200 billion annually

Mortality: 25-35%

Epidemiology (animals) Not known

Causes:HBCBDLDStepped on (pediatrics) ‘High rise’Kick injuriesPenetrating wounds Other blunt force trauma (crush injuries, etc.)

Primary Brain Injury Direct physical consequence of the impact

Skull fractures

Concussion

Contusions ○ site of impact (coupe) ○ opposite hemisphere where the displaced brain

contacts the skull (contrecoup)

Lacerations ○ hematomas

Secondary Brain Injury

Hours to days after insult

Major determinant of ultimate neurological outcome

Intracranial factors

Extracranial factorsSystemic factorsCellular factors

Cerebral Edema

Cytotoxic edema results from:Breakdown of cellular structuresDisruption of cell membrane function Disregulation of cellular ionic gradientIncrease in IC Na and Ca → increases osmolalityFluid accumulation in neurons and astrocytes

Vasogenic edema results from:Damage to BBB → changes in permeabilityEC fluid accumulation

Secondary Brain InjuryIntracranial factors

○ Increased ICP

○ Compromise of BBB

○ Mass lesions

○ Cerebral edema

○ Infection

○ Vasospasm

○ Seizures

Secondary Brain Injury Cellular factors

Disruption of the Na/K ATPase pump ○ ATP depletion ○ accumulation of IC Na ○ worsening cytotoxic edema○ accumulation of intracellular Na and Ca ○ depolarization

Excitotoxic injury: uncontrolled depolarization ○ increase in excitatory neurotransmitters (glutamate) ○ Ca influx into the cytosol ○ worsening cytotoxic edema ○ neurodegeneration of the CNS

Secondary Brain Injury Cellular factors

Cerebral lactic acidosis due to increased anaerobic metabolism○ Hyperkalemia → neuronal depolarization○ Inflammation○ Ischemia-reperfusion injury○ NO accumulation → excessive vasodilation

ROS, lipid peroxidation, cytokine production

Activation of the arachidonic acid, kinin, complement, and coagulation cascades

Systemic Insults

Acid-base disturbancesElectrolyte imbalancesHyper/hypocapniaHyper/hypoglycemiaHyper/hypothermiaHypotensionHypoxiaSystemic inflammation

Oxygen Delivery (DO2)

Decreased DO2 is the main perpetrator of secondary brain injury Further ATP depletion Anaerobic metabolism Lactic acidosis Cellular damage/death

DO2 = CaO2 x CO

CO = HR x SV

CaO2 = (Hb x 1.34 x SaO2) + (0.003 x PaO2)

Effect of anemia, pulmonary contusions, pleural space disease

Cerebral Blood Flow

15% of resting CO

20% total O2 consumed

Determined by: CPP PaO2

PaCO2 Cerebral metabolic demand

Monroe-Kellie Doctrine

Cranial compartment is incompressible Volume inside the cranium is fixed Cranium/contents create a volume equilibrium

blood (10%)CSF(10%)brain tissue (80%)

Any increase in volume of one must be compensated by a decrease in another

Intracranial Pressure Depends on volume of CSF, blood, and brain tissue

in the cranial vault Normal <15mmHg (5-12)

CPP = MAP – ICP Goals: CPP ≥ 70mmHg, SAP ≥ 90mmHg, MAP ≥ 80mmHg

Aggressive attempts to maintain CPP>70mmHg with IVF and pressors should

be avoided due to risk of ARDS – Level II

CPP <50mmHg should be avoided. Target is 50-70mmHg. Patients with

impaired autoregulation will tolerate higher CPPs - Level III

Intracranial Hypertension Major cause of post-traumatic neurological

morbidity/mortality

Limits cerebral perfusion

Promotes hypoxic/ ischemic injury

Compression of brainstem: depressed mental, cardiac, respiratory function and herniation/death

Intracranial Hypertension Humans treated when ICP >20mmHg

Accommodated by:Venous blood shunting out of the skull (can fall by 30-40%) Increased CSF absorption (can reduce the size of the ventricles

up to 90%)Brain tissue is somewhat compressible Hyperventilation → cerebral vasoconstriction and decreased

blood flow into the cranial vault

Intracranial volume can gain ~100-150ml (an average hematoma) in humans without significant increases in ICP

Autoregulation

Pressure: vascular smooth muscle maintains CBF via changes in CVR over MAPs of 50-150mmHg

Outside this range CBF is directly proportional to BP

Autoregulation Chemical: vasoconstriction/dilation in response to CO2

Hypoventilation → ↑PaCO2 → respiratory acidosis sensed by central chemoreceptors → vasodilation of cerebral vasculature, ↑CBF and ↑ICP

Hyperventilation → ↓PaCO2 → respiratory alkalosis sensed by central chemoreceptors → vasoconstriction of cerebral vasculature, ↓CBF and ↓ICP

1mmHg change in PaCO2 → 3-4% change in CBF

Autoregulation

Neurogenic: vasoconstriction/dilation in response to sympathetic and parasympathetic innervation

Factors affecting CBF

Hyper/hypocapnia Hypoxia Local acidosis Increased cerebral O2 demand Fever Seizures Increased sympathetic activity Systemic hypertension/hypotension

Cushing’s Response Marked elevations in ICP limit CBF

Ischemia causes the vasomotor center of the brain emits a massive SNS discharge

Systemic vasoconstriction/severe hypertension result to elevate MAP and maintain CPP

Hypertension is sensed by baroreceptors (carotids) resulting in a reflex bradycardia via PNS

Hypertension, bradycardia and decreased LOC = severe intracranial hypertension and IMPENDING HERNATION

Triage

Cardiovascular stability

Mentation

Major injuries

Physical exam

Complete PE

Assess other injuries

GCS

Full neurologic exam

Predicted probability of survival in 38 dogs during the 1st 48 hours after TBI

50% probability of survival for GCS of 8

MGCS category was not found to predict patient survival.

Gender, weight, age and presence of skull fractures did not predict survival

Total Score Severity Prognosis

3 - 8 Severe Grave

9 - 14 Moderate Poor to guarded

15 - 18 Slight Good

Modified Glascow Coma Score

Motor activity Score

Normal gait, normal spinal reflexes 6

Hemiparesis, tetraparesis, or decerebrate activity 5

Recumbent, intermittent extensor rigidity 4

Recumbent, constant extensor rigidity 3

Recumbent, constant extensor rigidity with opisthotonus 2

Recumbent, hypotonia of muscles, depressed or absent spinal reflexes

1

Modified Glascow Coma Score

Brain stem reflexes Score

Normal pupillary light reflexes and oculocephalic reflexes 6

Slow pupillary light reflexes and normal to reduced oculocephalic reflexes

5

Bilateral unresponsive meiosis with normal to reduced oculocephalic reflexes

4

Pinpoint pupils with reduced to absent oculocephalic reflexes 3

Unilateral, unresponsive mydriasis with reduced to absent oculocephalic reflexes

2

Bilateral, unresponsive mydriasis with reduced to absent oculocephalic reflexes

1

Modified Glascow Coma Score

Level of consciousness Score

Occasional periods of alertness and responsive to environment 6

Depression or delirium, capable of responding but response may be inappropriate

5

Semicomatose, responsive to visual stimuli 4

Semicomatose, responsive to auditory stimuli 3

Semicomatose, responsive only to repeated noxious stimuli 2

Comatose, unresponsive to repeated noxious stimuli 1

Level of consciousness Provides information about the functionality of the cerebral

cortex and the ascending reticular activating system

Normal

Obtunded - arousable with noise or gentle touch but have decreased responsiveness to the environment

Stuporous - responsive to noxious stimulation only

Comatose - not responsive to any stimulation

Pupils Respond to light

intact rostral brainstem, optic chasm, optic nerves, and retinae

Miosis diencephalon lesion (hypothalamus)

Initially mitotic and then become mydriatic progressive brainstem lesion

Normal to mydriatic, non-responsive pupils injury to oculomotor nerve in the brainstem ipsilateral to the injury

Bilateral mydriasis with no response to light irreversible midbrain damage and herniation

Anisocoria lateralizes lesion

Pupils Vestibulo-ocular reflex

physiologic nystagmus – lack of often indicates brain stem injury

Oculocephalic reflex (Doll’s eye) normal response of moving laterally

toward the side opposite the direction the head is turned

severe brain stem dysfunction if absent

Motor Function/Posturing

Decerebrate rigidity opisthotonus extensor rigidity of all limbs severely altered mentation lesion at or just rostral to the midbrain grave prognosis

Decerebellate rigidity opisthotonus forelimbs are in extension hindlimbs flexed (or sometimes normal) alert and aware lesion of the rostral lobe of the cerebellum

Diagnostics – Direct ICP measurement Rarely measured in veterinary patients Treatment goal <20mmHg ICP should be monitored in all salvageable

patients with severe TBI (GCS 3-8) and abnormal CT - Level II

ICP should be monitored in all patients with severe TBI (GCS 3-8) and a normal CT if 2 or more of the following exist at admission: age >40yo, abnormal posturing, hypotension - Level III

Diagnostics - CT

Skull fractures

Diagnostics - CT•

Multiple, small petechial

hemorrhages at the q gray-white matter

junction characteristic of diffuse axonal injury

Diagnostics - CT

Epidural

hematoma

Diagnostics - CT

Subdural hematoma with

midline shift and obliteration/

compression of ventricles

More common Higher mortality

3rd

Lat vent

Diagnostics - MRI

Hemorrhage

Goals of Treatment Maintain adequate CPP and CBF

Control ICP

Reduce cerebral metabolism

Maintain adequate BP

Avoid hypercarbia, hypoxemia

Treat the rest of the patient

Treat Intracranial hypertension

Reduce brain size Reduce blood flow Reducing CSF

removal of 3cc of CSF = ~10% decrease in ICP and ~2% increase in CPP

Surgical intervention Treatment should be initiated with

ICP>20mmHg – Level II

Mannitol

Osmotic diuretic Pulls free H2O from the intracellular and interstitial spaces of the brain

into the vasculature → reduction of cerebral edema

Transient volume expansion

Decrease in blood viscosity induces cerebral vasoconstriction and maintain CBF

Reduces RBC deformity → improved O2 carrying capacity

Free radical scavenging properties → limited IRI injury

In one study high dose mannitol (1.4g/kg) resulted in significant neurological improvement in humans with TBI versus low dose mannitol (.7g/kg)

Mannitol Risks:

osmotic diuresis can worsen hypovolemia, causing hypotension which offset the beneficial effects on ICP

precipitation of acute renal tubular necrosis ○ maintain serum osmolarity < 320 mOsm/L

What about exacerbation of ongoing intracranial hemorrhage?

○ not a concern

Mannitol is effective at for control of raised ICP at doses of .25-1g/kg. Hypotension should be avoided – Level II

Restrict mannitol use prior to ICP monitoring to patients with signs of herniation or progressive neurologic deterioration not attributable to extracranial causes – Level III

Hypertonic Saline Rapid rise in osmolarity causes fluid movement

from the interstitium and intracellular space to the intravascular space

Reduction of cerebral edema and decrease in ICP without adverse hemodynamic effects

First line therapy when intracranial hypertension exists with hypovolemia

HS encourages regional CBF (and therefore DO2) by minimizing endothelial cell swelling and promoting arteriolar dilation

Hypertonic Saline Modulates the inflammatory response by limiting

cellular adhesion and decreasing excitotoxicity

Shown to minimize vasospasm, promote local vasodilation, and limit endothelial cell swelling

Randomized study of patients with head trauma, persistent coma and ICH resistant to standard therapy, hypertonic saline was MORE effective than mannitol at reducing ICP

Furosemide

Brain Trauma Foundation no longer recommends to treat cerebral edema

No benefit in multiple studies

Potential for intravascular volume depletion → systemic hypotension → ↓ CPP

Steroids

CONTRAINDICATED

Increase morbidity/mortality

Side effects:hyperglycemia immunosuppressiongastrointestinal ulcerationdecreased wound healing

CRASH study Randomized controlled clinical trial

of >10,000 humans

Corticosteroid use:no effect on ICPincreased mortalityworse 2 week and 6 month outcome

Corticosteroids are not recommended for improving outcome or reducing ICP. In TBI patients steroid use has been shown to increase morality and are contraindicated – Level I

Fluid Therapy Fluids should never be restricted

Dehydration only minimally decreases ICP

Hypovolemia can significantly impair CPP

Overhydration should be avoided

Even one episode of hypotension (SAP<90mmHg) doubles mortality

Hypotonic crystalloids should be strictly

Glucose containing fluids should be avoided

Continuous BP monitoring with avoidance of hypotension

(SAP<90mmHG) - Level II

Fluid Therapy Intact BBB is impermeable to colloids

Compromise of the BBB with TBI and fluids may leak into the cerebral interstitium worsening vasogenic edema (?)

Benefit of restoration of MAP (and therefore CPP) far

outweighs this theoretical risk

SAFE trial (Saline vs. Albumin Fluid Evaluation) TBI patients resuscitated with albumin

(vs. .9%NaCl) had:○ a higher mortality rate ○ worse functional neurological outcome at 24m

Pressors

Dopamine has been shown to improve CBF after TBI without causing cerebral vasoconstriction

Vasopressin and norepinephrine can also be used. However, norepinephrine use may be associated with cerebral perfusion compromise (conflicting data)

Ventilation

1 episode of hypoxia (PaO2 <60mmHg) doubles mortality

Provide supplemental O2

Avoid placement of nasal O2

Intubate smoothly

GOALS/SETTINGS: SpO2 >97%, PaO2 >90mmHg

PaCO2 goal 35mmHg (35-40)

Oxygenation should be monitored and hypoxia (PaO2 < 60mmHg, SaO2 <90mmHg) avoided - Level III

Hyperventilation ↓PaCO2 → respiratory alkalosis → vasoconstriction of

cerebral vasculature → ↓CBF and ↓ICP

Routine therapeutic hyperventilation NOT recommended

Short-term, life-saving for patients with acute neurological deterioration and signs of impending herniation

Goal: PaCO2 of 25-30mmHg works within 30 seconds max effect 8min reduce ICP by 25%

Hyperventilation Excessive hyperventilation (PaCO2 < 25mmHg,

>30min) should be avoided worsen cerebral ischemia and secondary

neurological injury

Prophylactic hyperventilation (PaCo2 ≤ 25mmHg) is not recommended – Level II

Hyperventilation is recommended as temporary measure for reduction on increased ICP but should be avoided during the first 24hrs when CBF is critically reduced. If used, SjO2 and PbrO2 are recommended to monitor DO2 - Level III

Seizures Seizures reported in up to 54% of humans

Immediate: < 24 hrs Early: 24 hrs- 7d Late: > 7d

Worsen secondary injury hypoxia, hypercarbia, releasing excitatory neurotransmitters,

depleting energy stores and increasing ICP

Antiseizure prophylaxis controversial overall reduction in the risk of immediate and early seizures with

prophylactic treatment with phenytoin (humans) no benefit associated with treatment longer than 7 days

Anticonvulsants Diazepam - agent of choice for active seizuring

Phenobarbital - most common agent for longer term control markedly decrease activation energy of cerebral tissue cardiovascular and respiratory depressant effects

Other options: KBr, Keppra, Zonisamide

Induction of barbiturate coma with pentobarbital decrease metabolic demands hypotension/ hypoventilation can increase ICP

Prophylactic use of AEDs is indicated to decrease the incidence of early post traumatic seizures. However early post traumatic seizures are not associated with worse outcomes – Level II

Prophylactic use of AEDs is not recommended for late posttraumatic seizures – Level II

Hypothermia – proposed benefits

Reduced :metabolisminflammationcerebral edemabrain volume ICPglutamate levels cytokine release

Hypothermia - complications Iatrogenic hypothermia Decreased immunity Infection Coagulation derangements Hypotension Bradycardia Arrhythmias Decreased myocardial performance

Hypothermia

Data indicates prophylactic hypothermia is not significantly associated with decreased mortality when compared to normothermic controls

Preliminary data suggests that a greater decrease in mortality risk is observed when target temperatures are maintained for >48hrs

Prophylactic hypothermia is associated with significantly higher Glascow Outcome scores when compared to normothermic controls – Level III

11yo SF Wheaton HBC GCS 10 Seizures uncontrolled with traditional therapy Controlled hypothermia (91o-95oF) Mechanical ventilation Full recovery/discharged

Behavior changes reported 8 weeks

Hyperglycemia Associated with increased mortality and worse

neurological outcomes for TBI patients

Higher admission BG associated with lower GCSs

Sympathoadrenal response to injury

Patients with cerebral ischemia and hyperglycemia: increases free radical production increases excitatory amino acid release increases cerebral edema Increase cerebral acidosis altered cerebral vasculature

Hyperglycemia Cerebral acidosis - most important mechanism of

increased secondary brain injury with hyperglycemia

During ischemia the brain relies on anaerobic glycolysis → accumulation of lactate and H+ → cerebral acidosis

Tighter control of BG without reduction in nutritional support is recommended

Insulin CRI to maintain BG between 70 and 120mg/dl (<150)

Avoid glucose-containing solutions

52 dogs, 70 cats

BG within 1h of admit

BG significantly higher in TBI patients

Unlikely a stress response to hospitalization

BG significantly associated with severity

BG not associated with outcome

Supportive Care

Elevate head/neck 15-30o to facilitate venous drainage

Avoid jugular compression   Adequate analgesia Basic nursing care Nutritional support (enteral with promotility

agents) Antibiotics Serial neurological exams Continuous monitoring GI protectants

Indications for surgery

Repair/removal depressed skull fractures

Evacuation of hematomas

Debulking of tumors

Decompressive craniectomy to control severely elevated ICP and prevent brain herniation (when refractory to medical therapy)

Pre-oxygenate

Smooth induction imperative

Appropriate IV access

Appropriate monitoring

Opioids

Minimal adverse cardiovascular effects

Reversible

Adverse effectsrespiratory depression hypotensionappropriate dosing and ventilation = safeCRIs better to avoid peaks and troughs

Benzodiazepines Lack adverse intracranial effects

Lack adverse cardiovascular and respiratory effects

Do not reduce ICP

Do cause small reductions in cerebral O2 demands

Enable dose reductions of other drugs

Etomidate Offers cardiovascular and respiratory stability

? neuroprotection

In humans it’s associated with cerebral hypoxia and cerebral ischemia possibly due to: cerebral vasoconstriction hemolysis NO scavenging

At this time the use of this drug is not recommended with TBI

Ketamine Typically avoided - can ↑ ICP

With concurrent propofol administration it helps ↓ ICP

Inhibits NMDA receptor (predominant receptor type responsible for ischemic injury) and may reduce secondary brain injury

Doesn’t cause cardiovascular and respiratory depression

Demonstrated to increase cerebral O2 consumption

Promising research in status epilepticus

Dexmedetomidine

Does not appear to influence ICP in dogs

Reduction in HR and CO can impair CPP

Only be used at very low doses (~1mcg/kg/hr)

Only be used when analgesia with less cardiovascular effects is unavailable/not adequate

Barbiturates Neuroprotective

Reduction in: cerebral O2 requirements, CBF, ICP

Increased protection from excitatory neurotransmitter release

Reduce Na channel conduction and IC Ca entry into the brain limits free radical production, ROS, and IRI injury

Antioxidant effects

Reduce seizure activity

Disadvantages delayed anesthetic recovery, hypotension, respiratory depression

Propofol

possible modulation of GABA receptors antioxidant effects more rapid recovery

Disadvantagesnegative cardiovascular effectsrespiratory depression

Volatile anesthetics

Dose related effects on ICP

Lower concentrations ○ reduce cerebral metabolism ○ decrease in CBF, ICP

At <1.3% MAC isoflurane ○ suppression of metabolic activity persists ○ ICP increases ○ compromised of CCP due to vasodilation and

anesthetic induced hypoventilation/hypercapnia○ systemic hypotension detrimentally affect CPP

Volatile anestheticsHigher alveolar concentrations

○ cerebral pressure autoregulation is disrupted○ perfusion becomes dependant on MAP

If ICP normal low doses are acceptable

If ICP already elevated they should avoided

12wo IF Great Dane Owner fell on

GCS 13, hypothermic, hypotensive, obtunded

BW ↑ Na , ↑ K, ↓ BG

HPA axis disruption due to trauma: Central Diabetes Insipidus – vasopressin ACTH stimulation test = hypoadrenocorticism – steroids, DOCP Thyroid profile = hypothyroid - L-thyroxine Growth hormone decreased Gonadotropin releasing hormone decreased

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Questions?