Mannitol dose requirements in brain-injured patients

There is little information as to the optimal use of mannitol. To determine the dose-response relationship, the osmotic gradient required, and the time course of intracranial pressure (ICP) reduction produced by mannitol, eight patients with acute head injury were studied in whom ICP was monitored with a ventriculostomy and found to be elevated. Ventilation was controlled to a pCO2 of 25 +/- 3 mm Hg and all were paralyzed with Pavulon. None had received barbiturates. Before mannitol administration the intracranial volume-pressure response was determined. Mannitol was administered as a bolus of 0.25 gm/kg, 0.5 gm/kg, and in six patients, 1 gm/kg, separated by at least 8 hours. In all patients the ICP reduction with 0.25 gm/kg (41.3 +/- 10.2 mm Hg leads to 16.4 +/- 5.6, p less than 0.01) was equivalent to that achieved with the larger doses. Serum osmolality rises of 10 mOsm or more were associated with a reduction in ICP. Much smaller doses than those previously recommended were effective in reducing the ICP acutely, although at 5 hours there was a trend toward persistent reduction when the larger dose is used. This trend was small and indicates that smaller and more frequent doses are as effective in reducing the ICP while avoiding the risk of osmotic disequilibrium and severe dehydration.