Trauma is a common presenting complaint in the small animal veterinary emergency room and traumatic brain injury occurs in a high proportion of these patients.
Trauma is a common presenting complaint in the small animal veterinary emergency room and traumatic brain injury (TBI) occurs in a high proportion of these patients. Common causes of TBI in dogs and cats include motor vehicle accidents, animal interactions, falls, blunt trauma, gunshot wounds and other malicious human behaviors. A global view of the patient is critical when treating TBI. Both extracranial and intracranial priorities must be addressed. Life-threatening extracranial issues, such as penetrating thoracic and abdominal wounds or airway obstruction, as well as compromise of oxygenation, ventilation, or volume status must be identified and treated appropriately. Once extracranial factors have been addressed, the focus shifts to intracranial priorities, such as maintenance of adequate cerebral perfusion pressure (CPP), oxygen delivery to the brain, and treatment of acute intracranial hypertension.
The pathophysiology of head trauma can be separated into two categories: primary injury and secondary injury. Primary injury is a direct and immediate result of the traumatic event itself and may include concussion, cerebral contusion, hematoma, and skull fracture. Secondary injury occurs in the subsequent hours to days and results from a series of physiologic and biochemical events that perpetuate neuronal tissue damage. Both systemic and intracranial insults contribute to this phenomenon and can occur independently or in combination. Systemic derangements that contribute to secondary brain injury include hypotension, hypoxemia, and disorders of ventilation. Hypoventilation leads to increased cerebral blood volume and hypoxemia while hyperventilation results in cerebral vasoconstriction and reduced perfusion. Metabolic abnormalities, such as hyperglycemia, hypoglycemia, electrolyte imbalances and acid-base disturbances further perpetuate this phenomenon. Intracranial insults that further exacerbate neuronal tissue damage include increased intracranial pressure (ICP), compromise of the blood-brain barrier, mass lesion, cerebral edema, infection, vasospasm and seizure.
Because the skull is a rigid structure, the volumes of the 3 normal components of the intracranial space (the brain, cerebrospinal fluid and blood) must exist in a dynamic equilibrium. This relationship is summarized by [Vintracranial = Vbrain + VCSF + Vblood]. A sudden increase in any of these volumes without a compensatory decrease in one of the others, or the presence of an additional volume due to intracranial hemorrhage can lead to dramatic increases in ICP.
Cerebral perfusion pressure (CPP) is the net driving pressure leading to blood flow to the brain. It is defined as the difference between systemic mean arterial blood pressure (MAP) and intracranial pressure (ICP) [CPP = MAP – ICP]. Both primary and secondary brain injuries result in increased ICP. This combined with hypotension (a common sequela of trauma) lead to decreased CPP and worsening of cerebral injury.
In the normal brain, autoregulatory mechanisms maintain constant cerebral blood flow (CBF) over a wide range of MAP (50 mmHg – 150 mmHg). These autoregulatory mechanisms are commonly compromised in patients with TBI making them more susceptible to ischemic injury with decreases in MAP. Acute increases in ICP will often trigger the Cushing's Reflex, a characteristic combination of systemic hypertension and sinus bradycardia. The initial drop in CPP resulting from increased ICP leads to a dramatic increase of sympathetic tone, causing systemic vasoconstriction and increased cardiac output, ultimately leading to significant increases in MAP. Stimulation of baroreceptors in the aorta and carotid sinus by the increase in MAP triggers a reflex sinus bradycardia. The presence of the Cushing's Reflex in a patient with head trauma is a sign of a potentially life-threatening increase in ICP and should be treated promptly.
Because of the likelihood of multi-systemic injury associated with head trauma, initial diagnostics and patient monitoring should focus upon a global assessment of patient stability. An initial emergency database should consist of a packed cell volume and total solids to assess for hemorrhage, blood glucose to assess severity of injury, and a blood gas (venous or arterial) to assess perfusion, ventilation, oxygenation, and acid-base status. If possible, samples for a complete blood count and blood chemistry should be obtained prior to therapy to assess renal and hepatic function, as well as to screen for other systemic disease. In general, occlusion of the jugular vein is contraindicated in patients with TBI, as this can lead to increased ICP due to decreased venous outflow from the brain; therefore, samples should be obtained peripherally, or via peripherally inserted central catheters.
Imaging of the head is indicated in patients with localizing signs of brain dysfunction, moderate to severe neurologic deficits that do not respond to aggressive extracranial and intracranial stabilization, and patients with deteriorating neurologic status. These studies can yield information about targets of potential surgical intervention, such as intracranial hemorrhage, skull fractures, or cerebrospinal fluid leaks. Skull radiographs have low sensitivity in the assessment of patients with TBI and rarely yield useful diagnostic information. Computed tomography (CT) is a sensitive imaging modality that yields excellent detail for assessment of skull fracture, acute hemorrhage, and brain edema.
The overall duration and frequency of episodes of hypoperfusion and tissue hypoxia have been associated with poorer outcomes in people with TBI. Therefore, serial monitoring of these parameters is essential for successful management of these patients. Frequent qualitative assessment of tissue perfusion via mucous membrane color, capillary refill time, heart rate and pulse quality, as well as quantitative assessment of blood pressure (direct arterial blood pressure, Doppler or oscillometric techniques), oxygenation (pulse oximetry or arterial blood gas analysis), and ventilation (end-tidal capnography, arterial or venous blood gas analysis) are crucial. A minimal MAP of 80 mmHg should be targeted to decrease the risk of inadequate CPP. Continuous ECG monitoring should also be employed and if episodes of sinus bradycardia are noted, blood pressure should be assessed for evidence of the Cushing's reflex, which warrants aggressive therapy directed at lowering ICP.
Treatment priorities for patients with TBI can be divided into two broad categories; extracranial priorities and intracranial priorities. Successful management of patients with TBI is dependent upon addressing both categories.
Because of the high likelihood of multi-system trauma in patients with TBI, assessment of potential extracranial injuries is an essential part of the initial diagnostic workup. As with any severely injured patient, the basics of Airway, Breathing, and Circulation (i.e., the ABC's) should be evaluated and addressed as necessary. Airway patency should be assessed and endotracheal intubation or tracheostomy considered if complete or partial obstruction is present. Because hypoxia is common in patients with traumatic injury, supplemental oxygen is indicated in the initial management of all patients with significant head injury. If the patient is not able to maintain normal oxygenation or ventilation then mechanical ventilation should be employed to maintain CO2 at the low end of the normal range (e.g., venous PCO2 40-45 mmHg, arterial PCO2 35-40 mmHg).
Patients with TBI commonly present in hypovolemic shock, and volume resuscitation goals should be aggressive (MAP of 80-100 mmHg). For patients without electrolyte disturbances, normal saline (0.9%) is the best choice of the isotonic crystalloids, as it contains the smallest amount of free water and is least likely to contribute to cerebral edema. Synthetic colloids can have a more rapid and long lasting effect in hydrated patients, but are not effective in dehydrated patients. Patients with hypotension due to hypovolemia and concurrent increased ICP will benefit from a combination of a synthetic colloid (Hetastarch or Dextran 70) and hypertonic saline solution. Patients who do not respond to volume resuscitation require vasopressor support. Because CPP is dependent upon MAP, systemic hypotension must not be tolerated.
The main goals of intracranial stabilization are maintaining adequate cerebral perfusion by controlling ICP, reducing cerebral metabolism, and maintaining adequate systemic blood pressure. A number of medical and surgical therapies are available to achieve these goals, and successful management of TBI is dependent upon choosing the most appropriate interventions.
Mannitol is an effective therapy for patients with increased ICP, and has been shown to reduce cerebral edema, increase CPP and CBF, and improve neurologic outcome in TBI. It has a rapid onset of action, with clinical improvement occurring within minutes of administration, and these effects can last as long as 1.5-6 hours. Mannitol boluses of 0.5-1.5 g/kg have been recommended for treatment of increased ICP in dogs and cats. Mannitol may increase the permeability of the blood-brain barrier (BBB), an effect that is most pronounced when the BBB is exposed to the drug for prolonged periods of time. The increased permeability can allow mannitol to leak into the brain parenchyma, where it can exacerbate edema. To reduce the risk of this effect, the drug should be administered in repeated boluses rather than as a constant rate infusion. The diuretic effect of mannitol can be profound and can cause severe volume depletion; therefore, treatment must be followed with isotonic crystalloid solutions and/or colloids to maintain intravascular volume. If repeated doses are administered serum osmolarity should be monitored.
Hypertonic saline (HTS) is a hyperosmotic solution that may be used as an alternative to mannitol in patients with head injury. Because sodium does not freely cross the intact BBB, HTS has similar osmotic effects to mannitol. Other beneficial effects of HTS include improved hemodynamic status via volume expansion and positive inotropic effects, as well as beneficial vasoregulatory and immunomodulatory effects. Rebound hypotension is uncommon with HTS administration because unlike mannitol, sodium is actively reabsorbed in the kidneys, especially in hypovolemic patients. This makes is preferable to mannitol for treating patients with increased ICP and systemic hypotension due to hypovolemia. Combining HTS with a synthetic colloid can prolong this volume expansion effect. HTS is contraindicated in patients with hyponatremia, as it can cause rapid rises in serum sodium concentrations, leading to central pontine myelinolysis and delayed neurologic signs. In euvolemic patients with evidence of intracranial hypertension, both mannitol and HTS can have beneficial effects. If an individual patient is not responding to one drug, the other may yield a beneficial response.
Corticosteroids are potent anti-inflammatory medications, and have been recommended to treat a wide variety of disorders, including TBI. A recent clinical trial evaluating over 10,000 human adults with head injury showed that treatment with corticosteroids was associated with worse outcome at 2 weeks and 6 months post-injury. Due to the lack of evidence of any beneficial effect of corticosteroids after TBI, and strong evidence from the human literature showing a detrimental effect on neurologic outcome, corticosteroids should NOT be administered to dogs and cats with TBI.
Furosemide has been proposed for treatment of cerebral edema secondary to TBI either as a sole agent or in combination with mannitol. However, this has been called into question due to the potential for intravascular volume depletion and systemic hypotension, ultimately leading to decreased CPP. Furosemide should be reserved for those patients in whom it is indicated for reasons other than cerebral edema, such as those with pulmonary edema or oligo-anuric renal failure.
Cerebral vasodilation and blood pooling can cause increases in the total cerebral blood volume (CBV), and can contribute to increase ICP. Several techniques to decrease CBV have been described and have been shown to be effective in people with increased ICP. Elevation of the head by 15-30 degrees reduces CBV by increasing venous drainage, decreasing ICP and increasing CPP without deleterious changes in cerebral oxygenation. It is imperative that occlusion of the jugular veins be avoided by using a slant board to prevent bending the neck. Angles greater than 30 degrees may cause a detrimental decrease in CPP. Hypercapnia due to hypoventilation can cause cerebral vasodilation and increased CBV. Ventilatory support should be targeted at maintenance of normocapnia (arterial CO2 of 35-40 mmHg). In cases of severe, acute intracranial hypertension, short term hyperventilation to an arterial CO2 of 25-35 mmHg may be utilized to reduce CBV and ICP. However, chronic hyperventilation is not recommended due to evidence that the decrease in CBF leads to cerebral ischemia and worsens outcome.
Anticonvulsant therapy should always be instituted for patients with TBI who develop immediate or early seizures, but there is little evidence to support the utility of long term anticonvulsant therapy to prevent late seizures in these patients.
Presence and persistence of hyperglycemia have been associated with worse outcome in numerous clinical studies in human children and adults with TBI. Only one retrospective veterinary study has evaluated the association between hyperglycemia and TBI, and although an association between admission hyperglycemia and severity of neurologic injury was noted, there was no association between hyperglycemia at admission and survival. This is an active area of research, but until larger outcome studies are available, there is little evidence to support the use of insulin therapy in patients with TBI.
TBI can lead to increased cerebral metabolic rate (CMR) which can exacerbate cerebral ischemia and cellular swelling. Therefore, therapies targeted at decreasing CMR have the potential to reduce secondary brain injury. Inductions of barbiturate coma and hypothermia have been used in experimental studies and clinical trials in humans to reduce CMR. These techniques can effectively decrease ICP via reductions in CMR, and have been shown to improve outcome in human patients with refractory intracranial hypertension.
Although infrequently employed in veterinary medicine, several surgical procedures to address increased ICP have been described including CSF drainage and decompressive craniectomy. The use of decompressive craniectomy in human patients with TBI is controversial, and a large scale, randomized human clinical trial is currently underway (the RESCUEicp Trial), which will compare aggressive medical management with decompressive craniectomy in 500 patients with TBI.
Clinical experience would suggest that even patients with severe neurologic deficits at presentation can show marked improvement over the subsequent 24-48 hours. Therefore, serial neurologic exams are recommended. Client education is also of paramount importance, as persistent or permanent neurologic deficits in patients with TBI are not uncommon.