Increases in spinal fluid osmolarity induced by mannitol.

OBJECTIVE: Mannitol is widely used in hospitals worldwide to treat patients with high intracranial pressure and/or cerebral edema. One of the mechanisms by which mannitol is thought to affect intracranial pressure is by increasing the patient's serum osmolarity, but not the osmolarity in the brain or cerebrospinal fluid. In this way, mannitol is thought to increase the osmolarity gap between the brain and the blood, which in turn leads to removal of excess water from the brain. However, relatively little is known regarding long-term effects of mannitol on osmolarity of cerebrospinal fluid. We therefore sought to determine the effects of mannitol administration on the osmolarity of cerebrospinal fluid.

DESIGN: Controlled trial.

SETTING: University teaching hospital.

PATIENTS: Patients with severe head injury and patients with subarachnoid bleeding who required insertion of an intracranial probe.

MEASUREMENTS AND MAIN RESULTS: Serum and cerebrospinal fluid osmolarity were measured before and during mannitol administration in ten patients treated with mannitol for >or=72 hrs (group 1), ten patients treated for 24 to 48 hrs (group 2), and ten controls (group 3). Serum osmolarity increased quickly in all patients receiving mannitol (groups 1 and 2), whereas remaining constant in controls. Average cerebrospinal fluid osmolarity slowly increased in all patients receiving mannitol; cerebrospinal fluid osmolarity increased from (mean +/- sd) 291.5 +/- 4.0 to 315.5 +/- 4.5 mOsm/kg after 96 hrs in group 1 (p <.01), and from 288.9 +/- 3.5 to 296.9 +/- 6.2 mOsm/kg after 48 hrs in group 2 (p <.01). Cerebrospinal fluid osmolarity remained constant in controls (p <.01 for group 1 vs. group 3 and for group 2 vs. group 3, respectively). In group 1, the gap between serum and cerebrospinal fluid osmolarity initially increased (which was the desired effect), but later decreased first to baseline values and then to below-normal levels.

CONCLUSIONS: Long-term administration of mannitol can induce significant increases in cerebrospinal fluid osmolarity in patients with subarachnoid hemorrhage or severe head injury. This may be an undesirable and potentially dangerous effect. Therefore, cerebrospinal fluid osmolarity should be measured regularly in all patients receiving mannitol for longer than 24 hrs. If cerebrospinal fluid osmolarity increases, discontinuation or tapering of mannitol therapy should be considered.