Cerebral Blood Flow

The auto regulation of cerebral blood flow (CBF) can be defined as the ability to maintain the flow despite the increase or decrease in systemic blood pressure (pressure auto regulation). Auto regulation of the CBF is usually effective in a mean arterial pressure (MAP) of 60–140 mm Hg. Thus, if there is a reduction in MAP from 60 mm Hg, the CBF falls abruptly, leading to vasodilation and consequent vasoplegia promoting the engorgement of microcirculation and reduction in CBF. On the other hand, with an increase of MAP, the vessels constrict until the MAP reaches 140 mm Hg, level at which the pressure disrupt the vasoconstriction strength and promotes passive vasodilatation and increases the CBF.

Chemical auto regulation refers to the direct responsiveness of brain vasculature to the partial pressure of carbon dioxide in arterial blood (PaCO₂). Elevated PaCO₂ levels cause cerebral vasodilation, whereas decreased PaCO₂ levels promotes cerebral vasoconstriction.

Head Trauma

Traumatic brain injury is associated with high mortality, with death often occurring after elevation of intracranial pressure (ICP).

Brain damage can be conceptually divided into primary and secondary. The primary lesions occur immediately after impact and initiate a series of biochemical events which result in a secondary brain injury.

Immediately after the trauma occurs primary brain injury due to the rupture of intracranial structures resulting from direct injury to the parenchyma. Vascular injuries cause intracranial hematomas and vasogenic edema. Fractures of the skull, especially when unstable, promote continuous damage to the brain parenchyma and blood vessels.

Secondary injuries result from systemic extracranial events and also intracranial changes. The extracranial events often arise from episodes of hypotension and hypoxia that alter the regulatory mechanism of the CBF.

After a brain injury, massive depolarization of the neurons and supporting cells (astrocytes and glial cells) occur, generating an influx of ions (Na⁺ and Ca⁺ 2) inside the cells. In an attempt to restore the electrochemical gradient, a high amount of ATP is expended to the brain tissue. However, hypoxia and hypotension occurred after traumas induce the loss of CBF auto regulation and cause ATP depletion that generate intracellular edema due to low ATPase activity.

Release of glutamate into the extracellular medium occurs after depolarization. In general it is an excitatory neurotransmitter that directly or indirectly causes an influx of calcium into the cytosol.

The uncontrolled increase in intracellular calcium produces multiple cytotoxic effects. High concentrations of calcium lead to oxidative phosphorylation that elevates ATP depletion. Several enzymatic systems are activated including: protein kinase C, phospholipase, protease, endonuclease and synthesis of nitric oxide. The activation of phospholipase A2 starts the cascade of arachidonic acid resulting in the production of platelet activating factors and formation of oxygen free radicals.

The elevation of calcium into the cell is lethal to the nerve tissue, because it promotes uncontrolled activation of enzymatic systems and production of oxygen free radicals resulting in cellular necrosis by degradation of DNA, RNA and membranes structural proteins. Moreover, maintaining an ischemic environment perpetuates the processes mentioned above, leading to lactic acid accumulation in brain tissue.

Clinical Approach

The initial approach in patients with head trauma should focus on abnormalities that may cause imminent risk to life. It is important not to focus immediately on the neurological status itself, but in control airway, breathing and shock that usually occur in the politraumatic patient.

During stabilization of the patient it is important to monitor the mean arterial pressure (MAP) because of its intimate relationship with the CBF and brain perfusion.

A decrease in MAP of 50 mm Hg can cause reflexive vasoplegia which reduces the CBF. Thus, the animal must be constantly monitored to keep the MAP within 80–120 mm Hg. Animals with head trauma may have elevated ICP and hypoxemia resulting from trauma can aggravate this situation. The elevation of CO₂ promotes relaxation of cerebral vessels and consequent reduction of cerebral vascular resistance (CVR). As the CVR is inversely proportional to the ICP, a sharp drop of CVR incurs in the increase in ICP. Due to this, PaCO₂ should be maintained between 30–35 mm Hg.

After clinical stabilization the patients are subjected to the modified Glasgow coma scale in order to establish the degree of neuronal injury and then referred for diagnostic imaging. Computed tomography (CT) is the standard method for diagnosis of intracranial lesions caused by trauma and, in some situations, it may be more advantageous than MRI, such as: faster time to image acquisition, lower cost, provides better observation of acute bleeding and of cranial bones.

Treatment

The treatment of brain-injured patient should be instituted as soon as possible and should focus more on systemic support than in specific neurological therapies.

The normovolaemia is achieved by administration of an isotonic solution NaCl 0.9%. Osmotic diuretics such as mannitol, are very useful in the treatment of increased ICP by expanding plasma that reduces immediately the blood viscosity and increase the oxygen availability. Dose of 0.25 g/kg of mannitol has shown the same effectiveness in reducing intracranial hypertension as the dose of 1.0 g/kg, but acts for a short period of time. Repeated doses of mannitol increase diuresis, which may result in contraction of intracellular volume, dehydration and concomitant risk of hypotension and ischemia.

Although the role of anticonvulsant therapy in order to prevent post traumatic epileptic disorders is still uncertain, epileptic episodes may worsen intracranial hypertension. For this reason, it is recommended that all epileptic or convulsive activities are radically treated with anticonvulsants such as phenobarbital (2.0 mg/kg every 6–8 hours).

The use of corticosteroids in patients with head trauma is controversial and has been increasingly discouraged. Prospective, randomized, placebo-controlled studies (Corticosteroid Randomization after Significant Head injury - CRASH) performed in humans with head trauma who received high doses of corticosteroids have shown significant increase in mortality rate.

Basically, there are three forms of brain edema: the vasogenic edema (extracellular) due to acute trauma, inflammation and tumors that promote fluid extravasation from increased vascular permeability; cytotoxic edema (intracellular) that occurs in cases of severe tissue hypoxia and interstitial edema due to translocation of CSF to the periventricular tissue in hydrocephalic patients.

As brain-injuried patients are likely to develop cerebral hypoxia, they are also subject to cytotoxic edema in a late period. Despite the use of corticosteroids to be effective in the control of vasogenic and interstitial edema, its use in high doses has shown disadvantage in control of cytotoxic edema, and promote deleterious side effects.

Although it has been shown that, in normal dogs craniotomy associated with durotomy dramatically reduces the ICP, the value of craniotomy as a treatment of head trauma in dogs is still controversial. The craniotomy should be recommended, associated or not to cranioplasty with bone cement and screw, in cases where bone fragments penetrate the brain parenchyma or in cases of extensive injury to the skull.

More than clinical evidence of neurologic dysfunction, ICP monitoring is an important predictive mechanism to perform craniotomy. The use of an optical intra-parenchymal device for ICP monitoring was effective and safe in dogs and cats. In the author's experience, the use of this device has contributed to the treatment planning of animals, regardless of its high cost.

References

1.  Platt S. Evaluation and treatment of the head trauma patient. Companion Animal Practice. 2005;27:31–35.

2.  JHA SK. Cerebral edema and its management. Medical Journal Armed Forces of India. 2003;59:326–331.

3.  Platt SR et al. The prognostic value of the modified Glasgow coma scale in head trauma in dogs. Journal of Veterinary Internal Medicine. 2001;15:581–584.

4.  CRASH (trial collaborators). Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364:1321–1328.

5.  Freeman C, Platt SR. Head trauma. In: Platt SR, Garosi L. Small Animals Neurological Emergencies. London: Manson Publishing; 2012.

6.  Dewey CW, Da Costa RC, eds. Practical Guide to Canine and Feline Neurology. 3rd ed. Iowa: Willey Blackwell; 2016.