Furr and Reed Chapter 32: Central Nervous System Trauma

Traumatic Brain Injury Etiology

• In 44% of cases, injury was sustained to the poll subsequent to rearing and falling over backward during halter training or restraint

• Cause of trauma unknown in 35%

What fraction of horses presenting for head trauma have CNS injury?

• CNS injury only present in half of horses presented for head trauma

  • The other half present for fractures of the orbit, periorbital rim, and zygomatic, mandibular, or maxillary bones

  • Fractures may be linear, stellate, compound, comminuted, or depressed

Monro-Kellie Doctrine

Three nearly incompressible volumes (blood, CSF, and brain parenchyma) exist within the rigid cranial vault and an increase in volume of one of those compartments must increase ICP unless it is compensated by an equivalent decrease within the other compartment volumes

Injuries Sustained from Impact to the Poll in Horses that Flip Over

• Impact to the poll in horses that flip over can result in fracture of bones on the side and base of the calvarium but more commonly the bones remain intact and more serious injury occurs to the basilar bones as a result of strong traction forces from the rectus capitis ventralis muscles

• Fractures of the basilar (basisphenoid and basioccipital) and temporal bones associated with poll impact have been identified in 44% of TBI cases

• Rectus capitis ventralis muscles insert on the ventral aspect of the basioccipital and basisphenoid bones

  • Main flexors of the head

  • Originate at the cervical vertebrae

  • Young horses more susceptible

    • Behavior

    • Suture between the basilar bones remains open until 2-5 years of age

What injuries can result from impact to the dorsal surface of the head?

• Impact to the dorsal surface of the head may result in damage to the frontal or parietal bones and cerebral cortical injury or, more commonly, damage to the cervical vertebrae and SCI

  • CN XII may be injured

  • Occipital cortical injury can occur and the optic nerve be stretched

Fracture of the Petrous Temporal Bone Associated with THO

• Fusion of the temporal and stylohyoid bones, stricture of the external ear canal, and obliteration of the lumen of the tympanic bullae

• Fractures of the skull can lead to damage to the vestibular apparatus or cranial nerve VII

• Can get extension of infection in the middle/inner ear to the brain stem, cranial nerves, or hindbrain

Mechanisms of TBI

Blunt

Penetrating

Blast

Spinal Cord Injury

• Typically caused by collision with an immovable object or falling

• Hyperextension, hyperflexion, dislocation, and compression of the vertebral column can result in osseous damage and/or SCI

• Injury at the level of the occipital-atlanto-axial site is frequently not associated with fracture

  • Tearing or avulsion of the ligaments of the dens can result in compression of the spinal cord at the occipital-atlanto-axial region

• Injury to the caudal cervical spinal cord can occur in the absence of fracture, subsequent to local hemorrhage

• Fractures of the mid-thoracic to cranial lumbar region are often associated with forces sustained when a horse lands on its back

  • Often unstable fractures but muscle spasms can temporarily stabilize

• Increased incidence of luxation, subluxation, and epiphyseal separations in young horses due the cervical vertebral growth plates not closing until 4-5 years of age

• Compression injuries are associated with shortening of the vertebral body and result from a head-on collision with an immovable object

Predilection Sites for Spinal Cord Injury in Adults

Occipital-atlanto-axial region

C5-T1

Caudal thoracic region

Predilection for Spinal Cord Injury in Foals

Foals more susceptible than adults and suffer injury to C1-2 and T15-18

Pathophysiology of TBI

• Forces are transmitted to the intracranial soft tissues, the brain is shaken within the uneven bony interior of the skull and/or directly damaged by osseous fragments or foreign bodies

• Most severe damage generally takes place at the place of impact (coup), and/or opposite to the side of impact (contrecoup)

• Brain also subjected to rotational and shock wave forces

Prinicpal Mechanisms of TBI

• Focal brain damage due to contact injury resulting in contusion, laceration, and intracranial hemorrhage

• Diffuse brain damage due to acceleration-deceleration injury resulting in wide-spread axonal injury or brain swelling

Primary Insult in TBI

• Primary insult (primary damage, mechanical damage) occurring at the moment of impact

  • Exclusively sensitive to preventative but not therapeutic measures

  • Result of the biomechanical effects of the injury

  • Characterized by immediate and often irreversible damage to neuronal cell bodies, dendritic arborizations, axons, glial cells, and brain vasculature

  • Initial brain injury may be focal, multifocal, or diffuse

Secondary Insult in TBI

• Secondary insult (secondary damage, delayed nonmechanical damage) which represents consecutive pathological processes initiated at the moment of injury with delayed clinical presentation

  • In TBI mostly caused by brain swelling, with an increase in ICP and a subsequent decrease in cerebral perfusion leading to ischemia

  • Sensitive to therapeutic interventions

  • Complex cascade of molecular, cellular, and biochemical evens that can occur for days to months following the initial insult, resulting in delayed tissue damage

  • Hypoxia, ischemia, brain swelling, alterations in ICP, hydrocephalus, infection, breakdown of BBB, impaired energy metabolism altered ionic homeostasis, changes in gene expression, inflammation, and activation/release of autodestructive molecules occur and exacerbate the initial injury

Characteristics of Primary Injury after CNS Trauma

Mechanical injury

Hemorrhage

Diffuse axonal injury

Characteristics of Secondary Injury in the CNS

Vascular

• Impaired regulation of local and systemic blood pressure

• Impaired cerebrovascular and spinal cord blood flow autoregulation

• Blood flow mismatch

• Breakdown of blood-brain and blood-spinal cord barrier

• Vasospasm

Edema formation

Impaired oxygenation

Metabolic dysfunction

Ionic concentration alterations

Inflammatory tissue response

Excitoxicity and neurotransmitter accumulation

Oxidative stress

• Reactive oxygen species

• Lipid peroxidation

Influx of serum proteins, calpain proteases, and metalloproteinases

Cell death

• Necrosis

• Apoptosis

Systemic Characteristics of Secondary Injury After CNS Trauma

Hypoxia

Hypotension

Hyperglycemia

Fever

Seizures

What is the most important pathology in severe TBI in humans?

• Results from forces that rapidly rotate and deform the brain

• Encompasses a spectrum of abnormalities from primary mechanical breaking of the axonal cytoskeleton, to transport interruption, swelling, and proteolysis through secondary physiological changes

Results of Cascade of Secondary Injury

• Cascade of secondary injury resulting in necrotic and apoptotic cell death

  • Hemorrhage, ischemia, and the primary tissue damage lead to sequestration of vasoactive and inflammatory mediators at the injury site

  • Inflammation and endothelial damage causes derangements in normal cerebrovascular reactivity and contribute to a mismatch of oxygen delivery to tissue demand, resulting in local or diffuse ischemia

  • Uncontrolled glutamate release and failure of energy systems in neuronal and supporting tissues lead to elevated intracellular calcium concentrations and subsequent cell death

Consequences of Ischemia

• Major consequence of ischemia is reduced delivery of oxygen and glucose

  • Blood flow interruption leads to disruption in ion homeostasis (particularly Ca, Na, and K) and a switch to anaerobic glycolysis resulting in lactic acid production and acidosis

• Cell membrane lipid peroxidation with subsequent prostaglandin and thromboxane synthesis, formation of reactive oxygen species, NO, and energy failure occur

• Brain has a high metabolic rate so disruption of blood flow leads to compromise of energy-supplying processes leading to impaired nerve cell function and cell death

• Impaired mitrochondrial function and energy depletion leads to a loss in maintenance of membrane potentials and depolarization of neurons and glia

Cytotoxic Edema

• Cytotoxic edema develops due to failure of Na+/K+ ATPase pump and subsequent influx of water following Na+

  • Occurs in gray and white matter and decreases the extracellular fluid volume

  • When capillary endothelial cells are edematous, capillary lumen size will diminish, creating increases resistance to arterial flow

  • Capillary permeability not affected

  • Major decreases in cerebral function occur, stupor and coma common

Vasogenic Edema

• Vasogenic edema develops as a result of disruption of the BBB

  • Extravasation of blood components and water occurs, resulting in increased extracellular fluid accumulation

  • Cerebral white matter particularly vulnerable

  • Displaces cerebral tissue and increases ICP

What is blood flow to the brain controlled by?

Changes in diameter of resistance blood vessels and cerebral blood flow is controlled by autoregulation

Cerebral Perfusion Pressure Equation

CPP = MAP - ICP

What is the cerebral perfusion pressure remained within a range of?

50-150 mmHg

What is the stimulus to which the autoregulatory response of the vasculature responds?

Cerebral perfusion pressure

What does increased ICP lead to?

Decreased CPP and reduced CBF

What does decreased CBF result in?

Areas of ischemia and subsequent restriction of delivery of oxygen and glucose to the brain

What are intracranial hypertension and cerebral hypoperfusion associated with?

Poor outcomes

Cushing Response

Cerebral ischemia in the brainstem initiates a reflux during which systemic arterial pressure increases to preserve CPP and CBF

Brain-Heart Syndrome

Persistently increased ICP and reduction of CBF result in increased sympathetic discharge (catecholamines) with subsequent myocardial ischemia and development of cardiac arrhythmias

Intraaxial Vascular Damage

Intraparenchymal and intraventricular

Extraaxial Vascular Damage

Within the skull but outside the brain tissue

Epidural Hemorrhage

Between the dura mater and the skull

Subdural Hemorrhage

Between the dura mater and arachnoid mater

Subarachnoid Hemorrhage

Between arachnoid mater and pia mater

What does a CNS hematoma cause?

• Hematoma formation displaces brain tissue with possible sequelae of herniation, pressure necrosis, and brainstem compression

What does hemorrhage around the interventricular foramen or mesencephalic aqueduct cause?

May obstruct CSF outflow and lead to hydrocephalus

What is the severity of spinal cord injury related to?

The velocity, degree, and duration of the impact, and subsequent compression of nervous tissue

What are the forces that blunt spinal cord injury occur under?

Flexion, extension, axial load, rotation, and distraction

Primary Spinal Cord Injury

• Forces that produce mild primary mechanical insult result in cord concussion with brief transient neurologic deficits and when most severe result in permanent paralysis

  • Cord concussion with transient neurologic deficits is a result of local axonal depolarization and transient dysfunction

  • Permanent paralysis is a result of primary tissue injury followed by spreading of secondary damage that expands from the injury epicenter

• Primary injury is the initial mechanical damage following acute insult

  • Blood vessels broken, axons disrupted, and neuron and glial cell membranes are damaged

  • Consequences predominantly visible in the central gray matter

Secondary Spinal Cord Injury

• Following pathophysiological processes involving ischemia, release of chemicals from injured cells, and electrolyte shifts alter the metabolic milieu and trigger a secondary injury cascade

  • Pathologic changes may progress for weeks to months, even in the face of clinical improvement

  • Secondary injury responsible for expansion of the injury site and limiting restorative processes

• Target for therapeutic interventions

Acute Spinal Cord Injury

• Acute injury results in immediate hemorrhage and cell destruction within the central gray matter

  • Early, often progressive, hemorrhage is one of the hallmarks of acute SCI

  • Loss of microcirculation spreads over considerable distance cranial and caudal to the site of injury

  • Cord swells within minutes of injury due to hemorrhage and edema

  • Hemorrhage, edema, and hypoperfusion of the gray matter extends centripetally within minutes to hours resulting in central necrosis, white matter edema, and demyelination of axons

  • Spinal cord ischemia develops over several hours after injury and contributes to secondary injury

  • Mechanical disruption of microvasculature causes petechial hemorrhage and intravascular thrombosis which with vasospasm and edema causes local hypoperfusion and ischemia

  • Cord swelling that exceeds venous blood pressure results in secondary ischemia

  • Loss of autoregulation makes the cord vulnerable to systemic hypotension

  • Spinal cord injury worsened under ischemic and hypoxic conditions, important to maintain normotension after SCI

Ischemic/Hypoxic State of Spinal Cord Injury

• In ischemic/hypoxic state, cell metabolism altered from aerobic to anaerobic metabolism

  • Results in lactic acid accumulation, causing acidosis in nervous tissue, decreasing glucose and oxygen consumption

  • Lactic acid stimulates prostaglandin production, ADP release, platelet aggregation, thromboxane A2 release, vasospasm, vasoconstriction, and inhibition of neurotransmitter release

  • In hypoxic states, Na+/K+ ATPase pump is inhibited resulting in cell's inability to maintain its electrical polarity

    • Allows for accumulation of K+ extracellularly and Na+ intracellularly, contributing to edema

Free Radicals in Spinal Cord Injury

• Free radicals can cause progressive oxidation of fatty acids in cellular membranes (lipid peroxidation) through reactions with unpaired electrons

  • Oxidative stress can disable key mitochondrial respiratory chain enzymes, alter DNA/RNA and their associated proteins, and inhibit Na+/K+ ATPase

    • Induces metabolic collapse and necrotic of apoptotic cell death

  • NO production and excitatory amino-acid-induced calcium entry are considered important mediators of necrotic and apoptotic cell death

Excitotoxicity

Deleterious cellular effects of excess glutamate and asparate stimulation of ionotropic and metabotropic receptors

• Extracellular concentrations increased after acute SCI, which occurs through release from damaged neurons, decreased uptake by damaged astrocytes and through depolarization-induced release

Inotropic Receptors

• NMDA

• AMPA/kainite

• Extracellular calcium and sodium can pass down a concentration gradient into the cell or when activated can result in release of calcium from intracellular stores

Metabotropic Glutamate Receptors

• Coupled to G proteins that act as secondary intracellular messengers

• Increased intracellular calcium concentrations can trigger calcium-dependent processes that can lethally alter cellular metabolism, such as activation of lytic enzymes, generation of free radicals, impairment of mitochondrial function, spasm of vascular smooth muscle, and binding of phosphates with subsequent depletion of cell energy sources

Inflammation Following Spinal Cord Injury

• After SCI, the injury site is infiltrated by blood-borne neutrophils

• Later, blood-borne macrophages and monocytes are recruited, as well as locally activated resident microglia - phagocytize injured tissue

  • Produce cytokines such as TNF-a, interleukins, and interferons

• Suggested that early inflammatory phases are deleterious in natures, whereas later inflammatory events appear to be protective

• CNS injury-induced immune depression is characterized by apoptosis of splenocytes, impaired production of cytokines from leukocytes and leukopenia

  • Accompanied by a prolonged stress response in which levels of catecholamines and cortisol are elevated in the tissues, the circulation, or both after SCI

Clinical Signs of TBI

• Most common neurological deficit was ataxia (65%)

  • Followed by nystagmus (56%), abnormal mentation (56%), abnormal pupil size, symmetry, or pupillary light response (47%) and head tilt (44%)

  • 29% presented with a triad of clinical signs: ataxia, nystagmus, abnormal mentation

  • Most horses (~80%) tachycardic on presentation

Alpha 2 Agonists and TBI

• Alpha 2 agonists may transiently cause hypertension, which may potentiate intracranial hemorrhage, but xylazine has been found to cause a minor decrease in CSF pressure in normal conscious horses

  • Xylazine safe to use if the horse's head isn't allowed to drop to such a low position that postural effects could lead to physiological increases of intracranial pressure

Neurogenic Pulmonary Edema Following TBI

• Pathophysiology appears to be associated with a sudden increase in ICP which upregulates sympathetic signal transduction to ensure brain perfusion

• Immediate consequences are an increased tonus of venous and arterial vessels and increased myocardial function

• If systemic vascular resistance increases excessively, left ventricular failure and pulmonary edema may result

• Presence of protein-rich edema fluid suggests altered endothelial permeability within the pulmonary circuit which may be caused by acute pressure increase and neurohumoral mechanisms

Localization with Seizures, Delirium, Blindness, Mild Weakness

Cerebrum

Localization with Hypermetria, Intention Tremors, Abnormal Menace

Cerebellum

Localization with Depression, Obtunded, Various Cranial Nerve Abnormalities, Ataxia

Brainstem

Localization with Gait Abnormalities - Front Legs Normal, Rear Legs Abnormal

Thoracolumbar

Localization with Gait Abnormalities - Front and Rear Limbs Affected, Front Worse than Rear

C6-T2

Localization with Gait Abnormalities - Front and Rear Limbs Affected, Rear Worse than Front (by 1 Grade)

C1-C5

Localization with Gait Abnormalities - Front and Rear Limbs Affected, Rear Much More Severe than Front (>1 Grade Severity Difference)

L4-S2

Localization with Gait Abnormalities - Front Limbs Normal or Mildly Affected, Rear Limbs Affected, Tail Weakness, Bladder Dysfunction, or Perineal Hypalgesia

Sacral

What are the most common neurological syndromes following head trauma?

• Most common neurological syndromes following head trauma are a result of hemorrhage into the middle and inner ear cavities

  • Show central or peripheral vestibular disease and facial nerve damage

    • Recumbency, head tilt, neck turn, body lean, and circling, all toward the side of the lesion

    • Ipsilateral eye may be rotated ventrally and laterally

    • May be horizontal or rotary nystagmus with the fast phase away from the lesion

    • Central vestibular disease suspected when signs of brain stem disease or more cranial nerve deficits are present

    • Central vestibular lesions can result in a paradoxic vestibular syndrome - lesion located on the side opposite to that which is suspected from clinical signs

What affects the level of consciousness?

• Level of consciousness is affected by the degree of damage to the cerebrum and reticular activating system (RAS) in the brain stem

  • Immediately after cerebral injury there is a period of concussion with unconsciousness

    • Horse usually recovers in minutes to hours

    • Comatose horses can have irregular breathing pattern

      • Cheyne-Stokes breathing

      • Hyperventilation

  • Generalized seizures can occur after initial concussion

What can injury to the occipital cortex result in?

• Injury to occipital cortex can result in impairment of vision and menace response of the eye contralateral to the lesion

  • PLR should remain intact

What can injury to the parietal cortex result in?

• Injury to the parietal cortex can result in decreased facial sensation on the contralateral side

Severe Rostral Brainstem Injuries

• Associated with coma and depression due to damage to the RAS

• Strabismus, asymmetric pupil size, and loss of PLR can be present due to damage to CNIII

• Apneustic or erratic breathing reflects poor prognosis and bilaterally dilated and unresponsive pupils indicate irreversible brainstem lesion

• Can result in a decorticate posture, characterized by rigid extension of neck, back, and limbs

Injury to Caudal Brainstem

• Dysfunction of multiple cranial nerves, depression, and limb ataxia and/or weakness

• Distinguish between cranial cervical spinal cord and caudal brain stem by careful assessment of horse's mentation and function of cranial nerves X and XII

Cerebellar Injury

• Occur infrequently

• Intention tremor, broad-based stance, spastic limb movements, and absent menace response with normal vision

CT for TBI

• Changes observed after TBI include changes in the size, shape, and position of the ventricles, deviation of the falx cerebri, and focal changes in brain opacity

• Marshall and Rotterdam grading systems used for prognostication purposes

MRI for TBI

• Higher sensitivity for soft tissues

• Allows differentiation of gray/white matter, detection of abnormal tissue signals and mass effect shifts, swelling, edema, contusion, and hemorrhage

Electrodiagnostics for TBI

• Typically not indicated immediately after TBI

• After stabilization or during recovery, these techniques may provide information about certain levels of (dys)function

  • EEG - assessment of seizure activity

  • Brainstem auditory evoked response - examination of vestibular function

  • Visual evoked potential and electroretinography - visual function

CSF Analysis for TBI

• Cisternal CSF collection contraindicated if increased ICP suspected because of possibility of brain herniation through foramen magnum

• Lumbosacral safer alternative but can be normal despite a traumatic event

• Increased RBCs and erythrophagia suggestive of hemorrhage into the CSF following trauma

  • If hemorrhage is recent or iatrogenic, CSF usually clears with centrifugation, but if it persists, earlier hemorrhage should be suspected

• CSF lactate concentrations increased after trauma in horses

Clinical Signs of Spinal Cord Injury

• Neurologic signs are usually observed immediately after the accident but may occur weeks to months later due to delayed damage to the spinal cord caused by instability, arthritis, or bony callus

• Lesions causing recumbency mostly found in the caudal cervical or thoracic spinal cord

• Lesions of nonrecumbent horses are mostly found further cranial in the cervical spinal cord or in the lumbosacral cord

• Horses with vertebral fractures often display signs of pain in acute phase, reducing willingness to flex/extend/bend the neck or painful responses to palpation

• Pruritis affecting the C2 dermatome associated with C2 fracture reported

• Depression or loss of a segmental spinal reflex implies damage to either the afferent, efferent, or connecting pathways of the reflex arc

  • In acute SCI, a phase of spinal shock can occur in which there is profound depression in segmental spinal reflexes caudal to the level of the lesion

• Loss of sensation can occur distal to the level of SCI

• Diffuse sweating can be seen as a result of loss of supraspinal input to the preganglionic cell bodies of the sympathetic system

• Patchy sweating can be seen with damage to specific preganglionic or postganglionic nerve fibers

Schiff-Sherrington Syndrome

• Extensor hypertonus is present in otherwise normal thoracic limbs in patients with a severe thoracic lesion

  • Occurs infrequently

  • Short lived in the horse

Where is cord injury typically worse?

• Cord injury typically results in damage that is worse in the large myelinated motor and proprioceptive fibers compared to the smaller or nonmyelinated nociceptive fibers

  • Ataxia and loss of proprioception and motor function will occur prior to the loss of deep pain

Lower Motor Neuron Injury

Flaccid paralysis with hypo- or areflexia, muscular hypotonia, and neurogenic muscle atrophy

Upper Motor Neuron Injury

Loss of voluntary motor function, muscle tone may be increased, spinal reflexes may be normal to hyperactive

Clinical Signs o Lesions in C1-T2

Most common

Result in various degrees of tetraparesis to recumbency

Clinical Signs of Thoracolumbar SCI

Results in paraparesis to recumbency, may dog sit

Clinical Signs of Sacral Cord Damage

Can result in fecal and urinary incontinence, loss of use of tail and anus, muscle atrophy, and mild deficits of pelvic limb function

Clinical Signs of Sacrococcygeal Cord Injury

Hypalgesia, hypotonia, and hyporeflexia of the perineum, tail, and anus, or total analgesia and paralysis of those structures

Diagnosis of Spinal Cord Injury

• Radiography, ultrasonography, myelography, CT, MRI, nuclear scintigraphy, CSF analysis, nerve conduction velocity studies, electromyography, and transcranial magnetic stimulation

  • CSF analysis may be normal, particularly in very acute or chronic cases

    • Common abnormalities following SCI: xanthochromia, mild-to-moderate increased RBC and total protein concentrations, increased IL-6, INF-y, and TGFB

  • Electromyographic changes may not develop until 4-5 days following nerve damage

Goal of Acute Treatment of TBI

Minimize cellular injury and salvage brain tissue that is undamaged or reversibly damaged

• Aimed at optimizing CBF, maintaining oxygenation and energy substrate delivery, and promoting ionic homeostasis

Noninvasive Techniques for Screening for Intracranial Hypertension

Doppler ultrasonography derived pulastility index

Optic Nerve Ultrasonography

How to Assess CBF

• Can be assessed noninvasively using transcranial Doppler ultrasonography or invasively using laser Doppler flowmetry or thermal diffusion flowmetry

Methods of Measuring Brain Oxygenation

• Jugular venous bulb oximetry

  • Jugular bulb is the final common pathway for venous blood that drains the brain

  • Oxygen saturation at the jugular bulb indicates the balance between supply and oxygen consumption by the brain

• Direct brain tissue oxygenation tension measurement

• Near infrared spectroscopy

• Oxygen-15 PET

Initial Stabilization after TBI

• Normalization of mean arterial blood pressure and oxygenation, preventing and treating shock, and preventing hypotension

• Underlying cause of hypotension in trauma patients most commonly hemorrhage

  • Intravascular fluid most effective way to restore blood pressure

  • Avoid overhydration, can increase ICP and cause pulmonary edema

• Avoid carbohydrate-containing IV fluids early in treatment of head trauma patients

  • Glucose suppresses ketogenesis, and may increase lactic acid production by the brain

  • CO2 liberated from glucose metabolism could cause vasodilation and worsening of cerebral edema

Hypertonic Saline for Initial Stabilization for TBI

• Trials have shown higher systolic blood pressure and better survival in trauma patients resuscitated with hypertonic saline instead of isotonic crystalloids

  • Hypertonic saline may decrease ICP

  • Hypertonic saline increases serum sodium and osmolarity causing an osmotic gradient -> water diffuses passively from cerebral intracellular and interstitial spaces into capillaries -> decreased ICP

  • Mannitol works similarly but hypertonic saline has a better reflection coefficient (1.0) than mannitol (0.9)

  • Hypertonic saline may normalize resting membrane potential and cell volume by restoring normal intracellular electrolyte balance in injured cells

  • Hypertonic saline has positive effects on CBF, oxygen consumption, and inflammatory response at a cellular level

  • In horses administered IV as 5 or 7.5% solutions (4-6 ml/kg) over 15 minutes

    • Recent study showed that hypertonic saline (7.5%, 4 ml/kg) provided faster restoration of intravascular volume deficits than isotonic saline (0.9%, 4 ml/kg)

Contraindications for Hypertonic Saline in TBI

• Contraindications to hypertonic saline use are dehydration, ongoing intracerebral hemorrhage, hypernatremia, renal failure, hyperkalemic periodic paralysis, and hypothermia

Systemic Side Effects of Hypertonic Saline

• Systemic side effects include potential for coagulopathy, excessive intravascular volume, and electrolyte abnormalities

Noninvasive Procedures to Manage TBI

• Rapid intubation

• Adjusting head posture

• Body rotation

• Hyperventilation

• Hypothermia

• Hyperbaric oxygen

Invasive Procedures to Manage TBI

• CSF drainage

• Decompressive craniectomy

• Used when ICP is unresponsive to other treatments

Mannitol

• Induces changes in blood rheology and increases cardiac output -> improved CPP and cerebral oxygenation -> induces cerebral artery vasoconstriction and reduction in cerebral blood volume and ICP

• May diffuse through the BBB with prolonged usage, exacerbating elevation in ICP

• Associated with significant diuresis, acute renal failure, hyperkalemia, hypotension, and rebound

• Recommended to be used only when signs of elevated ICP or deteriorating neurological status suggests benefits may outweigh risks

Indications for Anti-Inflammatories for TBI

Combat inflammatory pathways of secondary injury mechanisms, improve comfort level, reduce fever

Hypothermia for TBI

• Reduced release of excitotoxins, reduction of free radical and inflammatory mediator formation, and reduction of BBB disruption

Corticosteroids for TBI

• Focal lesions appear to respond well to corticosteroid therapy, while diffuse intracerebral lesions and hematomas less responsive

DMSO for TBI

• Results in strong diuresis, protects cells from mechanical damage, reduces edema in tissue by stabilizing cell membranes, and acts as a free radical scavenger

• Increases tissue perfusion

• Transiently reduces increased ICP

Progesterone for TBI

• May modulate excitotoxicity, reconstitute the BBB, reduce cerebral edema, regulate inflammation, and decrease apoptosis

Methylphenidate for TBI

• CNS stimulant with dopaminergic and slight noradrenergic activity

• Neuroprotective effects attributed to methylphenidate like asparate inhibitors

Controlling Seizure Activity after TBI

• Seizure activity increases cerebral metabolic rate and is detrimental to secondary injury

• Diazepam, midazolam, phenobarbital, pentobarbital

• Intractable seizures may necessitate GA

  • Guaifenesin, chloral hydrate, barbiturates, and gas anesthesia

    • Barbiturates may have protective effect against ischemia by lowering cerebral metabolism and retarding peroxiation of lipids within brain cell membranes

  • Ketamine not recommended because it increases CBF and ICP

When are antibiotics warranted with TBI?

• Warranted when fractures are involved, hemorrhage increases chances of septic meningitis