Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure

The effect of mannitol (1.0 gm/kg) and furosemide (0.7 mg/kg), alone and in combination, on the blood-brain extracellular fluid and cerebrospinal fluid (CSF) osmotic gradient, elevated intracranial pressure (ICP), CSF and serum osmolality, and urine output was studied in 26 mongrel dogs. Mannitol and furosemide, when used together, produced a greater (62.4% versus 56.6%) and more sustained (5 hours versus 2 hours) fall in ICP than mannitol alone. This correlated with a prolongation of the reversal of the blood-brain osmotic gradient (-3.4 to + 38.5 mOsm/kg) and a rate of urine formation 15 times control values. There was a transient but not significant fall in serum Na+ with the combined treatment, but the arterial pressure did not vary from pretreatment levels. The results from this present study suggest that the distal loop diuretics in a dose of less than 1.0 mg/kg act synergistically with mannitol by causing preferential excretion of water over solute in the renal distal tubule, and thereby sustaining the osmotic gradient initially established by the mannitol infusion. It is possible, but unlikely in the doses used, that the additive effect of furosemide on reducing ICP in the presence of mannitol is due to interference with CSF formation or Na+ and H2O movement across the blood-brain barrier.