Medical Pharmacology Chapter 47: Brain Injury


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Cortical contusion >1cm in diameter 

  • "This is a scan of a patient who has sustained a severe head injury.

  • There is extensive bruising of the right side of the brain, showing up as a large, diffuse grey area.

  • You can also see that there are patches of white within the grey area. This represents bleeding.

  • The grey area represents swelling (edema). The area of the cortical contusion is outlined in purple.

  • You will normally find a centimetre scale at the right hand side of a CT scan. This scan would be classified on the Early Outcome Form as "Cortical contusion - greater than 1cm in diameter."

  • Scans provided by Mr Jonathan Wasserberg, Consultant Neurosurgeon;  Mr Bill Mitchell, Research Associate, Dept Neurosurgery, University of Birmingham.


Cerebral Contusion 
  • (Left) "The image above shows extreme contusion and hemorrhage involving the frontal and temporal poles.

  • These are areas that sit within skull pockets and are commonly injured when the brain moves quickly forward in a severe automobile accident.

  • Note the proximity of the olfactory bulbs to the frontal areas.

  • Patients often lose the sense of smell following these injuries."

  • (Right) "This image illustrates a number of contusions on the brain surface as well as deep within the cerebral convolutions." J. Michael Williams, PhD,  Neuropsychology


Head Injury  Background: Review

  • 5The incidence of head injury per year in the United States is about 200/100000 which corresponds to about 500,000 individuals exhibiting severe head injury [50,000 die prior hospitalization and the remaining 450,000 requiring hospitalization]. 

    • Of the 450,000 requiring hospitalization over 20 percent will exhibit some level of disability following recovery. Head injury is most likely to occur in the age group 15-24 years and is more likely to occur in males (2x-3x greater frequency). 

    • Most of the time severe head injury is associated with other injuries resulting in hypoxia, hypotension, and blood loss. 

    • Automobile (motor vehicle) accidents results in over half of all head injury is and in excess of 70% of head injuries that prove fatal.

  • 5Severe head injury classification utilizes the Glasgow Coma Scale in which neurological deficits are represented in terms of speech, motor function and eye opening.

    • Using a maximum score of 15, a Glasgow Coma Scale rating of age or less which lasts over six hours defines severe head injury. 

      • The Glasgow Coma Scale or Glasgow Outcome Scale may be useful in assessing ultimate outcome. 

      • The likelihood of mortality following severe head injury is closely associated with the initial Glasgow Coma Scale score although for any given score elderly patients exhibit a less favorable outcome compared to younger patients.

Modified Glasgow Coma Scale

Eye Opening

  • Spontaneous    4

  • To verbal command    3

  • To pain    2

  • None    1


Best Verbal Response

  • Oriented, conversing    5

  • Disoriented, conversing    4

  • Inappropriate words    3

  • Incomprehensible sounds    2

  • No verbal response    1


Best Motor Response

  • Obeys verbal commands    6

  • Localize to pain    5

  • Flexion/withdrawal    4

  • Abnormal flexion (decorticate)    3

  • Extension (decerebrate)    2

  • No response (flacid)    1



Glasgow Outcome Scale




Good recovery (GR)


Minor disabilities, but able to resume normal life.

Moderate Disability (MD)


More significant disabilities, but still able to live independently. Can use public transportation, work in an assisted situation, etc.

Severe Disability (SD)


Conscious, but dependent upon others for daily care.Often institutionalized

Persistent Vegetative State


Not conscious, though eyes may be open and may "track" movement.

Death (D)



  • 5The initial injury associated with head trauma is due to forces, often of millisecond duration, applied to the skull and brain. 

    • Secondary effects by contrast to the initial trauma may be quite serious and include brain swelling, and edema, intracranial bleeding, intracranial hypertension, and herniation. 

    • Factors that worsen the initial insult include hyperglycemia, anemia, hypotension, hypercarbia, and hypoxia-effects that may be preventable. 

    • Some time following the initial injury other serious effects may occur and include sepsis, infection, and seizures; and these effects must be either presented or managed aggressively.

  • In the majority of cases, secondary events influence the clinical course of head injury patients

    • One particularly important event is hypotension secondary to head injury. 

    • Post-head injury hypotension is associated with significant morbidity/mortality (frequency = 70%). 

    • The combination of hypotension and hypoxia adds to the likelihood of adverse outcomes (frequency = 90%). 

    • These observations emphasize the importance in limiting or avoiding the currents of post-head injury hypovolemic shock. The implication of these types of findings is that in the event the primary insult is survivable, secondary complications which themselves may have devastating consequences can and should be preventable

  • The category of primary head injury to brain tissue consists of concussion, contusion, laceration, and hematoma. 

    • Edema or contusion is a likely finding independent of the presence of a mass-lesion which might require surgery. 

      • Subsequent to the primary head injury event, cerebral edema may occur often after 24 hours, manifesting in increased white matter associated extracellular fluid. 

      • This type of cerebral edema is generally diffuse and may occur due to rapid onset intracerebral congestion & hyperemia.

      • Management of cerebral edema include subtler approaches such as hyperventilation, mannitol + furosemide-induced diuresis, and barbiturate administration with concurrent intracerebral pressure (ICP) monitoring.



Furosemide (Lasix)


  • Craniotomy is required for management of acute epidural, intracerebral and subdural hematoma is as well as for depressed skull fractures. 

    • Evacuation using burr holes is often required for chronic subdural hematoma treatment. 

    • Epidural hematoma associated with trauma is a relatively uncommon event associated with head trauma, but when it occurs it is often following automobile accidents. 

      • Unconsciousness associated with epidural hematoma follows from middle meningeal vessel or dural sinus lesions. 

      • Transient improvement in the patient including lucidity is associated with vascular spasm with clotting; however, rebleeding is likely within a few hours with attendant deterioration in patient status. In these circumstances, emergent surgical intervention is mandated, and even in the absence of radiological assessment. This eventuality is particularly likely if the bleed resulted from arterial damage. 

      • Epidural hematomas is derived from venous lesions are more likely to develop slowly allowing radiological evaluation.

  • Acute subdural hematomas may exhibit a range of clinical presentations that include limited or slight deficits to loss of consciousness with indications of mass effect lesions. 

    • Mass lesions may present with pupillary enlargement, unilateral decrebration, and/or hemiparesis. The most likely cause of subdural hematoma is trauma, although spontaneous events associated with neoplasms, aneurysms, or coagulopathies also occur. 

    • Acute subdural hematoma is defined by the appearance of symptoms within three days; subacute hematoma, within 3-15 days; and chronic subdural hematoma, within an two weeks. 

    • The patient population most likely to exhibit subacute and chronic subdural hematoma is the age group > 50 years. 

    • Subacute and chronic subdural hematomas may exhibit broad clinical presentations ranging from focal signs to reduce level of consciousness or organic brain syndrome development.

      • Intracranial hypertension is typically associated with acute subdural hematoma and require is aggressive intervention to reduce ICP, and manage cerebral edema and swelling. These interventions may be required before, during, and subsequent to hematoma surgical evacuation.

Normal Brain CT Scan (courtesy of Department of Emergency Services,San Francisco General Hospital, Educational Clinical Images [Web Managers: Preston Maxim, MD, Stephen Bretz, MD, Contributors: Preston Maxim, MD, Stephen Bretz, MD])

Cerebral Contusion (courtesy of Department of Emergency Services, San Francisco General Hospital, Educational Clinical Images [Web Managers: Preston Maxim, MD, Stephen Bretz, MD, Contributors: Preston Maxim, MD, Stephen Bretz, MD])

 Subdural Hematoma (CT scans) courtesy of Department of Emergency Services,San Francisco General Hospital, Educational Clinical Images [Web Managers: Preston Maxim, MD, Stephen Bretz, MD, Contributors: Preston Maxim, MD, Stephen Bretz, MD]


Epidural Hematoma

  • "History: This four year old child was brought to the emergency room after he was hit by a car. 

  • Findings: CT scan without contrast obtained in the trauma center reveals a high density lens shaped collection in the left occipital region. Discussion: Epidural hematomas are located between the dura and the skull.

  • The tight adhesion of the dura to the skull causes the typical biconvex shape.

  • This also accounts for the fact that epidural hematomas may cross dural attachments, but not skull sutures.

  • Most commonly, they occur when a skull fracture lacerates the middle meningeal artery or a major dural sinus". --Case courtesy of J. Keith Smith, M.D., Ph.D. J. Kevin Smith, M.D., Ph.D. T. L. Kamplain. UAB Department of Radiology.



Extradural hematoma


  • Intracerebral hematoma may present with minimal neurological symptoms to coma. 

    • Typically large, singular intracerebral hematomas are surgically evacuated. 

    • Intracerebral hematoma management often requires intracranial hypertension management and control of cerebral edema.


Intracerebral hematoma

  • " Intracerebral hematoma. (A) A moderately large hematoma is seen on a CT scan performed in the emergency room. B) Four hours later, after the patient's neurological condition worsened, a repeat CT scan reveals dramatic enlargement of the hematoma. The patient was taken immediately to surgery." AORN Journal, Volume 63 (May 1996), pages 854-867;Copyright AORN, Inc, 2170 S. Parker Road, Suite 300, Denver, CO 80231. (original link:  Health Resources: Neurosurgery On Call)


Temporal intracerebral hematoma

  • "...spontaneous left temporal intracerebral hematoma with moderate mass effect" resident: Bryan Payne, MD, attending: Deepak Awasthi, MD ;  Case Conference of the Neurosurgery Department at Louisiana State University School of Medicine in New Orleans

Brain Herniation

  • Left6,7"Schematic representation of various herniation pathways (1) subfalcine, (2) uncal (Transtentorial), (3) cerebellar, and (4) transcalvarium)

    Center: Brain herniation refers to displacement of a portion of the brain from its normal position through openings in the inelastic dura secondary to focal or diffuse intracranial pressure.

    • Recognition of the CT signs of brain herniation on the emergent head CT is critical to proper patient management.

    • The types of brain herniations are schematically illustrated...":a) " Subfalcial (cingulate) herniation ; b) uncal herniation ; c) downward (central, transtentorial) herniation ; d) external herniation ; e) tonsillar herniation.Types a, b, & e are usually caused by focal, ipsilateral space occupying lesions, ie., tumor or axial or extra-axial hemorrhage."- Copyright © 2000, 2001 John H. Harris, Jr., M.D. & Thea T. Troetscher, RN, used with permission in accord with site's educational use guidelines.) (Image template:  attribution, Gean, AD)

    Right:  High-resolution image, courtesy of Professor Alisa Gean, MD, University of California, San Francisco, San Francisco General Hospital.13 .  Professor Gean has authored the excellent textbook, "Imaging of Head Trauma".


Brain:  infarct, uncal herniation

  • (Left) "Bilateral symmetrical infarct of posterior cerebral arteries, secondary to bilateral uncal herniations compressing posterior cerebral arteries" KUMC pathology department, used with permission courtesy of Dr. James Fishback 

  • (Right ): "Distortion of midbrain due to uncal herniation.

    • This specimen shows the midbrain in a case in which herniation of medial temporal lobe structures has produced typical distortion of the normal configuration of the midbrain and displacement of midline structures toward the opposite side.

    • Secondary hemorrhages did not develop in this instance " University of Rochester (c), Neuropathology and Neuroimaging Laboratory, Ralph F. Józefowicz, MD John J. Miller, MD James M. Powers, MD 

(1) Cystic metastases (2) Perifocal edema  Copyright, CID, 17.07.97 ,(C.I.D. (Centre d'Imagerie Diagnostique), Diagnostic Imaging Center, Lausanne, Switzerland)

8Head Position vs ICP & CPP

As head-up position is increased, ICP may be reduced, but beyond 30o heads-up CPP is likely compromised. Second source:  Durward, QJ, Amadner, AL, Del Maestro, RF, et al:  Cerebral and vascular responses to changes in head elevation in patients with intracranial hypertension, J Neurosurg 59: 938, 1983.


7Monitoring Methods in Head Injury



Treatment Threshold


Intracranial Pressure (ICP)

ICP monitor localized in the ventricle; brain tissue, subarachnoid, epidural or subdural space

20-25 mmHg (LSU)

Hyperventilation, head elevation, sedation, CSF drainage, paralysis, barbiturate-induced coma or surgery

Blood Pressure (CP)

Arterial Line

< 100 mmHg

Vasopressors, fluid, blood replacement

Cerebral perfusion pressure (CPP)

CPP=MAP-ICP; MAP = mean arterial pressure

< or equal to 70 mmHg

Control ICP & BP

Jugular Bulb venous oxygen saturation SjvO2

Catheter (often fiberoptic) inserted into the jugular bulb

< 50% saturation

Control ICP & CPP

Brain Tissue oxygen monitoring PtiO2

microcathetic placed into frontal cerebral white matter

< 8.5 mm Hg

Control ICP & CPP

5Intracranial Measurement Methods

"These 'A'-waves (plateau waves) result when mean systemic blood pressure decreases below threshold  (and thus cerebral perfusion pressure) CPP falls below the ischemic threshold. Cerebrovasodilation then occurs in  response. In a non-compliant cranium, this vasodilation results in greatly increased intracranial pressure." picuBOOK an on-line resource for pediatric critical care, Joseph V. DiCarlo MD, Division of Pediatric Critical Care Medicine, Lucile Packard Children's Hospital, Stanford University, Palo Alto California 94304 USA


(Left) Image courtesy of Grant's Atlas of Anatomy  (Center, Right) Images from 9Using Jugular Venous Catheters in Patients with Traumatic Brain Injury, Kidd, KC and Criddle, L, Critical Care Nurse, vol. 21, No. 6, December 2001 original reference:$file/Casey.pdf

  • 9The internal jugular vein drains cerebral blood in a manner that results in limited contamination from extracerebral sources. Cerebral oxygen consumption is observed as a difference between arterial oxygen saturation and jugular bulb oxygen saturation (SaO2 - SjvO2). Brain oxygen consumption is tightly regulated; however, in the presence of brain injury, this autoregulation process operates abnormally causing mismatching between cerebral blood flow (CBF) and cerebral metabolic requirements. SjvO2 monitoring provides insight into factors influencing tissue oxygenation and oxygen consumption. 

    • 5, 9For example, cerebral oxygen desaturation reflected in the jugular bulb readings may occur within two days following traumatic brain injury. With normal SaO2 and PaCO2, SjvO2 should range between 60% and 80%; moreover hypoxemia is suggested if SjvO2 falls to less than 55%. Hyperemia (oxygen supply exceeding metabolic requirement) is suggested by SjvO2 values >75%.  Elevation of SjvO2 may suggest neuronal death since this condition results in diminished oxygen consumption.

    • 5Hyperemic states could follow from reduced metabolic need (coma, brain death) or from excessive CBF (e.g. severe hypercapnia.  The hypoxemia indicated by SjvO2 falling to less than 55% could herald ischemic brain damage. SjvO2 of less than 55% may be caused by increased metabolic requirement such as that accompanying seizures or fever providing such increased requirement is not matched by an commensurate enhancement of flow.  Alternatively, SjvO2 falling to less than 55% can also just reflect inadequate flow. Finally, systemic blood oxygenation state would influence in a more fundamental way jugular bulb saturation.

    • 5Despite the limitation of not detecting focal ischemia, jugular bulb venous oximetry can assist diagnosis of cerebral ischemia, excessive hyperventilation, or inadequate perfusion pressures.

Clark O2 Measurement Electrode

"The oxygen electrode is a simple device in which a current proportional to [O2] is generated by polarization of a Pt-electrode to reduce the O2. The configuration used for measuring respiration or photosynthesis is that suggested by Clark (the Clark oxygen electrode), and available in many commercial forms. In this configuration, the Pt-electrode area is kept small, so as to minimize the rate of consumption of oxygen, and the Pt and reference electrodes are separated from the reaction medium by an oxygen permeable membrane."--(A. R. Crofts), University of Illinois at Urbana-Champaign, Biophysics 354; 

"These electrodes have a thin organic membrane covering a layer of electrolyte and two metallic electrodes. Oxygen diffuses through the membrane and is electrochemically reduced at the cathode. There is a carefully fixed voltage between the cathode and an anode so that only oxygen is reduced. The greater the oxygen partial pressure, the more oxygen diffuses through the membrane in a given time. This results in a current that is proportional to the oxygen in the sample. Temperature sensors built into the probe on some advanced measurement systems allow compensation for the membrane and sample temperatures, which affect diffusion speed and solubility. The meter uses cathode current, sample temperature, membrane temperature, barometric pressure and salinity information to calculate the dissolved oxygen content of the sample in either concentration (ppm) or percent saturation t% Sat). The voltage for the reduction can either be supplied electronically by the meter (potentiometric oxygen electrode) or dissimilar metals may be used for the two electrodes, picked so that the correct voltage is generated between them (galvanic electrode). 

"Clark had the ingenious idea of placing very close to the surface of the platinum electrode (by trapping it physically against the electrode with a piece of dialysis membrane) an enzyme that reacted with oxygen. He reasoned that he could follow the activity of the enzyme by following the changes in the oxygen concentration around it, thus a chemosensor became a biosensor. Based on this experience and addressing his desire to expand the range of analytes that could be measured in the  body, he made a landmark address in 1962 at a New York Academy of Sciences symposium in which he described how "to make electrochemical sensors (pH, polarographic, potentiometric or conductometric) more intelligent" by adding "enzyme transducers as membrane enclosed sandwiches". The concept was illustrated by an experiment in which glucose oxidase was entrapped at a Clark oxygen electrode using dialysis membrane. The decrease in measured oxygen concentration was proportional to glucose concentration. In the published paper (Clark, L.C. Jnr. Ann. NY Acad. Sci. 102, 29-45, 1962), Clark and Lyons coined the term enzyme electrode. Clark's ideas became commercial reality in 1975 with the successful re-launch (first launch 1973) of the Yellow Springs Instrument Company (Ohio) glucose analyser based on the amperometric detection of hydrogen peroxide. This was the first of many biosensor-based laboratory analysers to be built by companies around the world."--This text has been compiled from the biography of Clark available in the Internet.

8CBF vs MAP relationships in the presence and absence of cerebrovascular autoregulation 

8In the absence of the normal autoregulatory cerebrovascular perfusion system (-- line) abnormally low cerebral blood flow can occur even with relatively normal mean arterial pressures. In the presence of head injury or subarachnoid hemorrhage, then, inadequate cerebral perfusion can occur even with reasonable, normotensive blood pressures. Even slight hypotensive responses are sufficient to promote cerebral ischemia.[Bouma GJ, Muizelaar JP, Choi SC et al:  Cerebral circulation and metabolism after severe traumatic brain injury:  The elusive role of ischemia. J Neurosurg 75: 685, 1991;  Ishii, R:  Regional cerebral blood flow in patients with ruptured intracranial aneurysms.  J Neurosurg 50:  587, 1979.]

Schematic lateral view of the cervical spine

  • 11Schematic lateral view of the cervical spine. Note the odontoid (dens), the predental space and the spinal canal. (A=anterior spinal line; B=posterior spinal line; C=spinolaminar line; D=clivus base line) (c) 1999 David Klemm. 


Type II dens fracture

  • 11"A type II dens fracture. Lateral radiograph shows a fracture through the base of the odontoid process (dens) with the dens and C1 posterior to C2 (arrow indicates fractured base of dens)." Figure on right (c) 1999 David Klemm; 

  • 12"Fractures of the dens are commonly classified according to a scheme proposed by Anderson and D'Alonzo into types I, II, and III.

    • Type II fractures are the most common, and consist of a fracture through the base of the dens, at its junction with the C2 body.

    • Type II fractures have a very high incidence of nonunion if not surgically fused. If the fracture extends through the upper body of C2, it is classified as type III.

    • Type III fractures usually heal completely with external immobilization. The type I fracture is an avulsion fracture of the tip of the dens. This is an extremely rare injury."


Jefferson fracture

  • 11"Jefferson fracture. Anteroposterior tomogram at the craniocervical junction demonstrates lateral mass of C1 (arrows) lying lateral to the lateral masses of C2 (arrowheads) on both the left and right sides as a result of spread of the ring of C1. Figure on right (c) 1999 David Klemm"


Jefferson fracture

  • 11"Jefferson fracture. Computed tomographic image through ring of C1 shows the anterior arch fracture (small arrow). Another small fragment (curved arrow) is shown lateral to the dens. The posterior arch fracture (arrowhead) on the right is not clearly demonstrated on this cut. Figure on right (c) 1999 David Klemm"


Hangman's fracture

  • 11"Hangman's fracture. Lateral radiograph reveals markedly increased prevertebral swelling (two short arrows) associated with the fracture at the posterior aspect of C2 pedicles (medium arrow).

  •  Displacement is obvious by following the posterior spinal line (long arrow).Figure on right (c) 1999 David Klemm"


Types  of Cervical Spine Injury

Spine Level


Stability Assessment

Mechanism/Clinical Comment

Radiological Assessment


Jefferson Fracture

Moderately Stable

Burst Fracture; follows from axial load or vertebral compression

Displaced lateral aspects of C1 on odontoid view, predental space > 3 mm


Alantoaxial subluxation

Highly Unstable

Occurs in Down's syndrome patients, rheumatoid arthritis and similar disease

Asymmetric lateral bodies on odontoid view, increased predental space


Odontoid fracture

Highly unstable


may require CT for adequate visualization


Hangman's fracture


occurs with sudden deceleration (hanging) and with hyperextension as in automobile accidents

"Bilateral pedicle fracture of C2 with or without anterior subluxation; lateral view is required"

Any Level

Flexion teardrop injury

Highly unstable

Sudden and forceful flexion

"Large wedge off the anterior aspect of affected vertebra; ligamentous instability causes alighment abnormalities"

Any Level

Bilateral facet dislocations

Highly unstable

Flexion or combined flexion/rotation

"Anterior displacement of 50% or more of one cervical vertebra on lateral views"

Any Level

Unilateral facet dislocations


Flexion or combined flexion/rotation

"Anterior dislocation of 25 to 33% of one cervical vertebra on lateral views; an abrupt transition in rotation so that lateral view of affect vertebra is rotated; lateral displacement of spinous process on anteroposterior view"

Lower or cervical or upper thoracic

Clay shoveler's fracture

Very stable

Flexion, such as when picking up and throwing heavy loads (such as snow or clay)

"Avulsion of posterior aspect of spinous process; frequently an incidental finding"

6,6bIn-Line Stabilization

5, 6,6bFollowing a hypnotic and muscle relaxant administration intubation proceeds even if the cervical spinal status is uncertain.  In this method, one assistant maintains in-line stabilization with the occiput held firmly to the backboard (hands are placed along the side of the head with fingertips on the mastoid holding the occiput down) .  The second assistant applies cricoid pressure.  Note that the posterior portion of the cervical collar remains in place.

  • 6The approach involving oral intubation with anesthesia and relaxation with in-line stabilization with the patient's occiput held securely on the backboard has been determined to be reasonable based on clinical trials.

    • However, this orientation limits attainment of the "sniff" position and makes laryngoscopy more challenging. 

    • The point however is to reduce atlanto-occipital (A-O) motion.

      • Normal laryngoscopy is associated with significant A-O extension, an important point given that devastating spinal cord injury may be often associated with atlanto-occipital region pathologies which happened to be difficult to assess radiologically. 

    • With the patient secured on the backboard has described earlier, visualization of the glottis may proceed with a relatively reduced degree of A-O extension.

      • Laryngoscopy in this situation reduces A-O extension probably because of greater compression of the soft tissue structures of the tongue and mouth floor (compression involves performing laryngoscopy against the assistant's counterpressure). 

    • For a number of reasons including radiologic evidence of instability, significant pre-existing neurological deficit, or if neck movement is associated with severe pain, alternative intubation approach is can be considered.

    • 8Awake fiber-optic intubation and then awake positioning, as noted earlier, is one approach.

      • Moreover, newer airway management instruments such as the Bullard laryngoscope, light wand, or Augustine intubating airway may be considered.

Bullard laryngoscope (original link,


Augustine Guide



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