Pathophysiology

Traumatic brain injury (TBI) in veterinary patients occurs most commonly secondary to road traffic accidents. Other common causes include kicks to the head, falls, gunshot wounds and animal bites.

CBF is driven by systemic arterial pressure but is dependent on several factors such as BP, cerebral metabolic rates, blood oxygen levels and carbon dioxide levels. The brain has an intrinsic ability to maintain CBF despite fluctuations in cerebral perfusion pressure (CPP). This ability is known as autoregulation. A constant CBF occurs between MAPs of 50 and 150 mm Hg. Outside of this range, blood flow to the brain will be dependent on systemic arterial circulation. A functional and intact blood-brain barrier is required for proper function of autoregulation. Therefore, loss of autoregulation following head trauma is related to disruption of the blood-brain barrier and a decline in CPP. CPP is dependent on a balance between MAP and ICP:

• CPP=MAP−ICP → Elevations in ICP can have a significant impact on CPP, leading to decreased brain perfusion. Ischaemia and a loss of autoregulation occur with a CPP <40 mm Hg.

Failure of autoregulation allows CBF to passively follow arterial pressure and be less responsive to changes in oxygen delivery.

The relationship between CPP, CBF and CVR is:

• CBF=CPP/CVR.

CVR depends primarily on blood viscosity and vessel diameter, therefore CBF is kept constant by fluctuations in CVR to compensate for alterations in CPP, which can occur due to MAP.

Following injury, CBF is often significantly reduced due to associated elevations in ICP (≥12–20 mm Hg). Factors that decrease CBF include oedema, haematomas, compression of vessels from mass effect and vasospasm. Additionally, trauma significant enough to cause TBI probably causes some degree of systemic shock and hypotension which may further reduce CBF.

Reduction in CBF due to raised ICP can lead to brain ischaemia. A series of physiological responses, when CBF declines, are in place to prevent this. Reduced blood flow to the vasomotor centres in the brainstem leads to reduced carbon dioxide removal. Subsequent elevation in local carbon dioxide concentrations stimulates the sympathetic nervous system to increase MAP. The result is systemic hypertension to maintain blood flow to the brain. However, as the baroreceptors located in the aorta and carotid sinus both detect systemic hypertension, a signal is sent to the vagal centres of the brainstem leading to reflex bradycardia. This phenomenon is referred to as the Cushing reflex. Therefore, concurrent systemic hypertension and bradycardia can indicate elevated ICP in head trauma patients.

Primary Injury

Primary, or biomechanical injury, describes the injury to the brain tissue from direct trauma and the forces applied to the brain at impact. An impact to the skull exerts the following forces on the brain: acceleration, deceleration and rotational forces. The superficial grey matter is most susceptible to the forces of acceleration, leading to haemorrhage or contusion and tearing of neuronal tissue. The rotational forces have more of an impact on the deeper white matter of the brain, causing concussive injuries and axonal damage. The roughly spherical shape of the skull and the propagation of rotational forces after injury direct these forces into the deeper tissues of the brain. Additionally, penetrating injuries can cause fractures, haemorrhage and direct damage to the brain parenchyma.

Secondary Injury

After impact, a cascade of biomolecular events occurs causing continued and progressive brain pathology. A series of cellular reactions begins at the time of impact and continues after the injury. This secondary brain injury has a significant effect on outcome and can lead to continued death of neurons and glial cells. The primary mediators involved in secondary brain injury include oxygen free radicals, excitatory amino acids (i.e., glutamate) and nitric oxide.

Intracranial Pressure

The brain is protected within the bony confines of the skull, where it exists in equilibrium with CSF and blood. The pressure exerted between the brain and the skull is the ICP, which is normally between 5 and 12 mm Hg in dogs and cats. The skull is relatively inelastic, limiting the volume that can exist within the cranial cavity. The space within the cranial vault is occupied primarily by three components: brain parenchyma, CSF and blood.

The Monro-Kellie doctrine describes the relationship between these components and their ability to compensate for increases in volume within the cranial cavity. After head trauma, the volume of the intracranial contents within the skull may increase due to haemorrhage, oedema or CSF accumulation. The brain has the capacity to tolerate small increases in volume by adjusting the size of one of the three components, primarily CSF. Shunting CSF to the spinal subarachnoid space, decreasing CSF production and increasing CSF absorption can rapidly decrease the intracranial CSF volume. CSF production does not typically affect elevations in ICP unless its drainage is obstructed, leading to obstructive hydrocephalus. Additionally, venous blood can be redirected out of the cranial cavity and CBF will decrease to compensate for ICP elevation. The ability of the brain to adjust for increases in ICP by decreasing the volume of CSF and blood is called compliance. During this time of compensation, the patient’s clinical signs will remain relatively normal, unless the trauma primarily injured the parenchyma (e.g., laceration, puncture wounds). Once compliance is exhausted, small increases in volume will result in dramatic elevations in ICP, which will be accompanied by a rapid decline in the patient’s neurological status. This ability to compensate is more effective if the increase in volume occurs slowly. With continued elevation of ICP, brain herniation can result.

Systemic Assessment

Initial assessment should involve evaluation of the patient’s respiratory and cardiovascular systems. An airway must be established, if necessary, through endotracheal intubation. Breathing patterns may be affected by thoracic trauma, but may also be secondary to brain injury. Auscultation of the thorax may detect pulmonary pathology or cardiac arrhythmias. Oxygen support should be given as necessary and mechanical or manual ventilation may be required with severe pulmonary injuries. Traumatic pneumothorax may require thoracocentesis or chest tube placement to allow proper ventilation. The cardiovascular system should be evaluated by monitoring heart rate and BP and by electrocardiography. Arterial blood analysis and lactate concentrations may provide additional information regarding systemic perfusion and respiratory function.

Repeated temperature assessment is important. Cerebral metabolic rate (CMR) is proportional to body temperature and increases by 5–7% per Celsius degree. Hyperthermia should be avoided in all patients and cooling techniques should be considered if this is noted. Hypothermia reduces the CMR and decreases the CBF by approximately 5% per degree of reduction in body temperature. Temperature instability in the brain-injured patient may be a grave prognostic sign.

Once the patient is stable, consider:

• Radiographs of the chest and abdomen to evaluate for pulmonary contusions, pneumothorax and abdominal injuries.
• Evaluate the abdomen through radiography and ultrasonography for the presence of free fluid, blood or urine, which may require additional therapy.
• Radiographs of the cervical vertebrae as fractures and luxations of these bones may occur.

Neurological Assessment

Neurological evaluation serves to determine whether there are neurological deficits suggesting structural neurological lesions, where the lesions are located and the severity of the lesion(s). Detection of a spinal and/or peripheral nerve lesion can affect the prognosis of any patient with head trauma. Without any extracranial lesions, the prognosis associated with head trauma is dependent on the location and severity of the parenchymal lesions.

Assessment of neurological status should initially be performed every 30–60 minutes. This allows for monitoring efficacy of treatment and early recognition of deterioration. The assessment should include evaluation of state of consciousness, motor function and reflexes, pupil size and responsiveness, position and movement of the eyes and breathing pattern. The evaluation of pupil and eye function is the most accurate way brainstem function can be assessed, and this is the most important part of the examination for prognosis. A scoring system has been developed to provide an objective assessment and allow for rational diagnostic, treatment decisions and prognosis (Modified Glasgow Coma Scale).

Diagnosis

A diagnosis of head trauma is based primarily on a compatible history and clinical signs of intracranial neurological dysfunction. Additional tests (CT and MRI) to confirm the location and the extent of the injury should be reserved for patients who do not respond to initial treatment or for patients who deteriorate despite aggressive therapy. Both imaging modalities require anaesthesia, which can destabilize the head trauma patient unless the patient is in a coma on presentation.

Treatment

Fluid Therapy

The goal of fluid therapy of the head trauma patient is to restore a normovolemic state. It is deleterious to dehydrate an animal to reduce cerebral oedema. Aggressive fluid therapy and systemic monitoring is required to ensure normovolemia to maintain adequate CPP. Crystalloid, hypertonic, and colloid fluids should be given concurrently to help restore and maintain blood volume following trauma. Crystalloids are usually given initially for the treatment of systemic shock. Crystalloid solutions will extravasate into the interstitium within one hour of administration requiring additional fluid resuscitation. Hypertonic and colloid fluid therapy can rapidly restore blood volume using low volume fluid resuscitation; additionally, colloids, remain in the vasculature longer than crystalloid fluids. These fluids should be used with caution as without concurrent administration of crystalloid solutions, hypertonic and colloid solutions can lead to dehydration. Other benefits of hypertonic fluids include the ability to improve cardiac output, reduce inflammation after trauma; the high sodium content of hypertonic saline draws fluid from the interstitial and intracellular spaces subsequently reducing ICP. Hypertonic saline may be preferred in hypovolemic, hypotensive patients with increased ICP. Contraindications to its administration include systemic dehydration and hypernatremia. Colloids allow for low volume fluid resuscitation especially if total protein concentrations are below 50 g/L or 5 g/dL. These fluids also draw fluid from the interstitial and intracellular spaces but have the added benefit of staying within the intravascular space longer than crystalloids.

Systemic blood pressure may require additional treatment to maintain adequate CPP. A MAP of 80–100 mm Hg should be the target blood pressure. Hypotension should initially be treated with fluid resuscitation; however, persistent hypotension may require treatment with vasoactive agents (i.e., dopamine 2–10 mg/kg/min). Additionally, systemic hypertension may occur as a sequela to intracranial hypertension (Cushing reflex) and should be treated by aggressively treating elevated ICP; the use of additional drugs to modulate the blood pressure should be avoided unless all attempts to lower ICP have been exhausted.

Oxygen Therapy and Ventilation

Control of PaO₂ and PaCO₂ is mandatory as will affect cerebral haemodynamics and ICP. The goal of oxygen therapy and management of ventilation is to maintain the partial pressure of oxygen in the arterial blood supply (PaO₂) greater than or equal to 90 mm Hg and the PaCO₂ below 35–40 mm Hg. If the patient can ventilate spontaneously and effectively, supplemental oxygen should be delivered via ‘flow-by;’ confinement within an oxygen cage prevents frequent monitoring. Face masks and nasal catheters should be avoided if possible as they can cause anxiety which may contribute to elevations of intracranial pressure.

Diuretics

ICP can be aggressively addressed with the administration of osmotic diuretics. Osmotic diuretics such as mannitol should not be given to any patient without being certain that the patient has been volume resuscitated. Mannitol improves CBF and reduces ICP by decreasing oedema, expanding the plasma volume and reducing blood viscosity, which improves CBF and delivery of oxygen to the brain. Additionally, assists in scavenging free radicals, which contribute to secondary injury processes. Vasoconstriction occurs as a sequela to the increased partial pressure of oxygen leading to an immediate decrease in ICP. Mannitol (0.5–2.0 g/kg) should be given as a bolus over 15 minutes to optimize the plasma expanding effect. Mannitol reduces brain oedema over about 15–30 minutes after administration and has an effect for approximately two to five hours. Repeated dosing of mannitol can cause diuresis leading to reduced plasma volume, increase osmolarity, intracellular dehydration, hypotension, and ischemia. Therefore, adequate isotonic crystalloid and colloid therapy is critical to maintaining hydration. Currently, there is no evidence to support that mannitol is contraindicated in the presence of intracranial haemorrhage as has been suggested.

Seizure Therapy

Seizures should be treated aggressively to prevent worsening of the secondary effects in the brain parenchyma due to associated brain hypoxia and subsequent development of oedema. Seizure activity may occur immediately following trauma or may be delayed in onset. The need for antiseizure prophylaxis after severe brain trauma remains controversial in human medicine. Some patients may require long-term management of seizure activity with antiepileptic medications. However, if maintenance therapy is continued beyond 7 days and seizure activity is not noted over a 3–6 month period, antiepileptic treatment may be slowly withdrawn.

Surgery

Surgical intervention is reserved for patients that do not improve or deteriorate despite aggressive medical therapy. Surgery may be indicated to remove haematomas, relieve ICP or address skull fractures.

Corticosteroids

Corticosteroids are no longer recommended in head trauma patients. Their use has been extensively evaluated in people, which has shown no beneficial effect and may even result in worse morbidity and mortality rates. Detrimental effects of corticosteroids include immunosuppression, hyperglycaemia and gastrointestinal disturbances.

References

1.  Kuo WK, Bacek LM, Taylor AR. Head trauma. Vet Clin North Am Small Anim Pract. 2018;48:111–128.

2.  Dewey CW, da Costa RC. A Practical Guide to Canine and Feline Neurology. 3rd edition. John Wiley & Sons, Inc.; 2016.

3.  DiFazio J, Fletcher DJ. Updates in the management of the small animal patient with neurologic trauma. Vet Clin North Am Small Animal Pract. 2013;43:915–940.

4.  Platt SR, Olby NJ. Neurological emergencies. BSAVA Manual of Canine and Feline Neurology. 4th edition. 2013.

5.  Platt SR, Garosi L. Head trauma. Small Animal Neurology Emergencies. 1st edition. CRC Press; 2012.

6.  Friedenberg SG, Butler AL, Wei L, Moore SA. Seizures following head trauma in dogs: 259 cases (1999–2009). J Am Med Assoc. 2012;241:1479–1483.