Traumatic Brain Injury

Traumatic Brain Injury
Adam R. Lancaster, DVM, DACVECC

Intracranial physiology

Cerebral perfusion pressure is the driving force of blood into the calvarium and is the major determinant of cerebral blood flow. Cerebral perfusion pressure is defined as the mean arterial pressure minus the intracranial pressure (CPP = MAP – ICP). Intracranial pressure (ICP) is defined as the pressure exerted between the skull and the intracranial tissues. A normal ICP is less than 10 mmHg. Cerebral blood flow (CBF) is blood flow to the brain per unit of time. In states of health, cerebral blood flow remains constant over a wide range of cerebral perfusion pressure (CPP) via the process of autoregulation. Once the mean arterial pressure drops below 50 mmHg, cerebral blood flow is directly dependent on CPP and thus MAP.

The Monroe Kellie Doctrine states that ICP is determined by the volume of three components within the skull: the CSF, blood and brain parenchyma. Under normal circumstances these components exist in a state of balanced equilibrium. Because the skull is a rigid compartment, changes in one compartment MUST cause a reciprocal change in another compartment in order to keep ICP the same. This accommodation is known as intracranial compliance and is accomplished by fluid shifts in the brain vasculature and CSF pathways. In health, this is termed autoregulation.

Intracranial compliance (autoregulation) prevents large changes in CPP associated with fluctuations in blood pressure and ICP. This is accomplished by fluid shifts in the brain vasculature and CSF. If ICP increases past the limits of compensation then CPP is compromised; this is termed the loss of autoregulation. Autoregulation occurs via two mechanisms. The first mechanism is called pressure autoregulation and is a change in cerebrovascular resistance in response to changes in mean arterial pressure. In health, this allows for constant cerebral blood flow between mean arterial pressures of 50-150 mmHg. The second mechanism is termed chemical autoregulation and leads to vasodilation or vasoconstriction of cerebral vasculature due to changes in PaCO2. Autoregulation is often disrupted with traumatic brain injury, and disruption of these mechanisms contributes to secondary injury.

Severe elevations in ICP lead to the cerebral ischemic response, also called the Cushing reflex. This occurs when the elevations in ICP lead to a decrease in CBF and a resulting increase in PaCO2. This triggers the sympathetic nervous system leading to hypertension and baroreceptor-mediated bradycardia.

People often use the terms head trauma and traumatic brain injury (TBI) interchangeably. While these terms are similar, they have different meanings. Head trauma is any injury to the head that may or may not result in injury to the brain. Traumatic brain injury may occur secondary to head trauma and is the result of both primary and secondary injuries.

Pathophysiology of traumatic brain injury

Traumatic brain injury may occur from a variety of events including motor vehicle accidents, hit by cars, dog bite wounds, penetrating trauma, falls and missile injuries. The degree of TBI that occurs is a result of both primary and secondary injury. Primary injury is the physical disruption of structures and may include contusions, hematomas, lacerations and vasogenic edema. Primary injury is a direct result of the event and is beyond the control of the clinician.

Secondary injury occurs as the result of the release of excitatory neurotransmitters and the release of reactive oxygen species and pro-inflammatory cytokines. The degree of secondary injury can be affected by the clinician. Systemic contributors to secondary brain injury include hypotension, hypoxia, hypo- or hyperglycemia, hypo- or hypercapnia and hyperthermia. Failure to prevent secondary injuries can lead to cerebral edema, increased ICP and ultimately death.

Patient assessment

All trauma patients should undergo a primary survey. At this point, it is important to recognize and treat shock and other concurrent injuries quickly as these may worsen neurologic injury. In addition to the primary survey, additional neurological assessment is performed on patients that may have suffered TBI. This neurologic assessment includes assessment of state of consciousness, breathing pattern, pupil size and responsiveness, ocular position and movements and skeletal motor responses.

The Modified Glasgow Coma Scale (MGCS) was developed to more objectively assess the degree of neurologic injury in veterinary patients. The MGCS assesses motor activity, brain stem reflexes and level of consciousness and assigns a score of 1-6 in each category for a total score of 3-18. The higher the number, the less injury and the better the overall prognosis. It is important to remember a few important points. First, the MGCS may be affected by systemic shock, so shock needs to be resolved before assigning a score. For instance, it is not unusual for a patient that is in shock to be non-ambulatory even without any neurologic dysfunction. Second, as with any scoring system, caution should be exercised when attempting to predict prognosis in an individual patient.


Treatment of TBI includes therapy aimed at restoration of perfusion and reversal of shock (extracranial therapy) and therapies directed at decreasing ICP (intracranial therapy). Fluid therapy should be initiated in all patients showing signs of shock or decreased perfusion. Historically, there have been recommendations to limit the volume of fluid administered to TBI patients due to the concern that aggressive IV fluid administration may exacerbate cerebral edema. However, we know that hypotension is associated with worse outcomes, and there are limited data to support the idea that dehydration diminishes cerebral edema. Therefore, these recommendations for fluid restriction are now firmly contraindicated. Various types of fluids may be used in resuscitation of the patient suffering from TBI including isotonic crystalloids, hypertonic saline and colloids. Isotonic crystalloids are a reasonable fluid choice for resuscitation. Care must be exercised to avoid excessive administration of these fluids as they can lead to edema throughout the body including cerebral edema. Colloid solutions may also be considered. Some concerns have been expressed that administration of colloidal solutions may worsen cerebral edema if they cross the blood-brain barrier. However, colloid oncotic pressure is not the driving force of cerebral water content, and therefore ICP, so this should not be a major concern. Hypertonic saline may be the fluid of choice for resuscitation of patients with TBI due to its volume expansion as well as positive effects on ICP.

Oxygen supplementation should be administered to any patient confirmed or suspected to be suffering from hypoxia. Hypoxia exacerbates brain injury, and human patients with TBI and hypoxia have been shown to have double the mortality of patients with TBI without hypoxia. There are numerous ways to administer oxygen to patients including flow-by, oxygen cages, nasal lines, transtracheal, and endotracheal intubation and ventilation.

Assessment of appropriate ventilation is also necessary. Due to its effects on cerebral vasculature, carbon dioxide is the main determinant of cerebral blood flow and cerebral blood volume. Hypoventilation leads to an increase in carbon dioxide, vasodilation, increased blood flow and increases in ICP. Hyperventilation leads to a decrease in carbon dioxide, vasoconstriction, decreased blood flow and ischemic injury. Both of these states have been shown to perpetuate secondary injury. The goal of ventilation management is normocapnia (a PaCO2 of 35-45 mm Hg). Brief periods of aggressive hyperventilation may be necessary with acute deteriorations in neurologic status. However, excessive hypocapnia should still be avoided.

Spikes in intracranial pressure should be minimized by elevating the head 15-30 degrees, not occluding the jugular veins for venipuncture, taking off constrictive collars, and avoiding use of jugular catheters and neck wraps unless absolutely necessary. When elevating the head of the patient it is better to use a stiff board to elevate the entire patient than place towels under the neck as this may compress the jugular veins.

The mainstay of treatment of intracranial pressure elevations is hyperosmolar therapy. Two main drugs are available, hypertonic saline and mannitol. Mannitol has been extensively studied and is considered a first-line medical therapy for ICP elevations. It acts as an osmotic diuretic, successfully decreasing the ICP for up to 6 hours. Due to its osmotic diuresis, mannitol therapy may exacerbate hypotension, and therefore administration must be followed by appropriate crystalloid therapy. Other problems with mannitol include a ceiling effect, rebound effect and exacerbation of ongoing intracranial hemorrhage (clinical relevance uncertain).

Hypertonic saline (HTS) is a crystalloid fluid that is hypertonic to the blood. This hypertonicity has a direct osmotic effect on cerebral water content by pulling fluid from the brain into the vasculature. HTS also acts as a potent expander of intravascular volume (in contrast to mannitol) and therefore reverses shock while simultaneously decreasing intracranial pressure. Benefits of hypertonic saline include avoidance of hypotension, lack of ceiling effect and increased reduction of ICP compared to mannitol. Side effects of HTS include cerebral dehydration, volume overload and hypernatremia.

There are numerous ancillary therapies that have been described for use in traumatic brain injury. Glucocorticoids have historically been used in TBI for their anti-inflammatory effects. While the administration of glucocorticoids has a proven benefit on reduction of inflammation and ICP in patients with intracranial neoplasia, no such benefit has been proven for patients with TBI. In fact, a large human trial called the CRASH trial actually showed that high doses of steroids increased mortality in patients with traumatic brain injury. The administration of glucocorticoids may cause hyperglycemia, immunosuppression, delayed wound healing, gastric ulceration and exacerbation of catabolic states. Given the lack of documented benefit and potential side effects glucocorticoids are considered contraindicated in traumatic brain injury.

Glycemic control refers to the maintenance of a normal blood sugar in a patient. Hyperglycemia is common in patients with traumatic brain injury, and these patients have been shown to have increased mortality and worsened neurologic outcomes in people. In dogs and cats the degree of hyperglycemia on presentation has been associated with the severity of traumatic brain injury. What is not clear however is whether hyperglycemia itself worsens secondary brain injury or if it is simple a marker of more severe disease.

Anticonvulsant therapy is currently recommended for one week in all human patients suffering from TBI. This is because post-traumatic seizures are relatively common. Long-term anticonvulsant therapy is not currently recommended unless the patient develops seizure activity. The current role of anticonvulsant therapy in dogs and cats is not known. It may be used on a case-by-case basis.

Pain management is very important. Pain increases catecholamine release and may lead to hypertension, two conditions that may increase ICP. Opioid pain medications are often the treatment of choice, but doses may need to be reduced if the blood-brain barrier is disrupted. Opioids are effective analgesics, readily reversible and have no major effect on intracranial pressure. Other drugs that may be considered include benzodiazepines, ketamine, dexdomitor and lidocaine. Benzodiazepines have no effect on ICP but also do not have analgesic effects on their own. In combination of an opioid they can be very effective for sedation and to decrease stress in patients. Ketamine is an effective analgesic, however it does have some properties that may not make its use ideal in TBI patients. These include increased cerebral oxygen consumption and increased catecholamine release. Dexdomitor should be used cautiously due to its negative effect on cardiac output. Lidocaine may be used in a CRI in conjunction with opioids and other analgesics. It has no detrimental effect on ICP and may reduce secondary brain injury.

Injury to the central nervous system is an independent predictor of GI bleeding, and therefore routine stress ulcer prophylaxis is recommended. Hypothermia has been proposed to be neuroprotective by decreasing cerebral metabolic rate, reducing the threshold for critical oxygen delivery, reducing calcium mediated toxicity and reducing glutamate induced excitotoxicity. However, numerous side effects may occur, and there are conflicting results in the literature regarding outcome. At this time routine induction of hypothermia cannot be recommended. Permissive hypothermia may play a role. Early enteral nutrition should be considered in these patients.

In humans with subdural or extradural hematomas and deteriorating neurologic status, surgical intervention is standard of care. In other situations, the benefit of surgical intervention has not been established. The role of surgical management in veterinary patients with TBI is still unclear.