Reduction of Brain Mass

Because of the presence of the blood-brain barrier, which is relatively impermeable to sodium and chloride ions, the movement of water into and out of the brain cells is primarily determined by the osmotic gradient. An effective osmotic diuretic that is frequently used to treat elevated ICP is 20% mannitol. Given as a bolus at 0.5-1.0 g/kg, the action is immediate in onset, but peaks at 30 minutes, lasting for about 90 minutes. The loop diuretic, furose-mide, potentiates the actions of mannitol, may also have direct ICP lowering effects, and is often given as an adjunct. The effects of manni-tol on systemic hemodynamics are complex, with initial reduction of systemic vascular resistance, followed by intravascular volume expansion, which may be accompanied by systemic hypertension. Patients with poor cardiac function may develop acute pulmonary edema with infusion of mannitol. With the onset of diuresis, contraction of intravascular volume occurs, and this would result in hypotension if fluid replacement is inadequate. The complications from mannitol therapy include fluid overload, dehydration and renal failure.

During mannitol therapy, electrolytes and serum osmolality should be monitored frequently, and serum osmolality should not exceed 320 mOsm. Although the primary mechanism of mannitol is based on the osmotic gradient, it may also cause reflex vasoconstriction and reduce CSF production. Patients who become refractory to mannitol often would respond to hypertonic saline infusion (3% or 7.5%). Despite numerous clinical reports attesting to its efficacy, there have been no randomized clinical trials on the use of hypertonic saline, and rebound intracranial hypertension is a potential complication.

In patients with vasogenic edema associated with tumor, steroids are effective, and dexam-ethasone 10 mg is generally given every 6 hours. Steroids in general are considered to be con-traindicated in patients with traumatic brain injury and ineffective in patients with sub-arachnoid hemorrhage or ischemic stroke. In patients with spinal cord injury, high-dose methylprednisolone has been shown to improve functions when given within 8 hours. In most centers, when seen within 3 hours, these patients are given methypredisolone 30 mg/kg bolus, followed by 5.4 mg/kg/h for 24 hours, and for 48 hours if seen between 3-8 hours (NACIS III). The improvement is, however, marginal, and many query if the benefits outweigh the risks of pneumonia and infection. Nevertheless, in view of the efficacy of steroid in spinal cord injury, the use of high-dose methylprednisolone in head injury is being re-examined, and a randomized trial aiming to enroll 20,000 patients is currently under way [6].

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