The Value of Hypertonic Mannitol Solution in Decreasing Brain Mass and Lowering Cerebrospinal-Fluid Pressure

Abstract

T HE value of a chemical or pharmacological agent that temporarily would lower cerebrospinal-fluid pressure and decrease the mass of the brain is apparent to neurosurgeons. Since Weed and 1VfcKibben 4e,47 demonstrated that various hypertonic solutions could accomplish these effects, many agents have been tested. 6,14,17,22,29,45,49,55 Each of these substances has been found to have certain disadvantages or toxic effects. The use of hypertonic urea for these purposes originally was proposed by Fremont-Smith and Forbes, 15 and Wolff and Forbes, 64 and was restudied by Fremont-Smith eta/., ~3 Smythe et a/., 39 and Javid and Settlage. ~5 This material was difficult to prepare for sterile intravenous injection, but when lyophilized urea and invert sugar became available it found wide acceptance. ~4,42,44 While hypertonic urea frequently is effective in lowering cerebrospinal-fluid pressure and decreasing the mass of the brain, there are certain theoretical and practical objections to its use. Urea is distributed throughout total body water, n.4~ although it does equilibrate relatively slowly with brain water and cerebrospinal fluid, s.33 Thus, unless the urea administered were excreted fairly rapidly, one would expect dissipation of its osmotic gradient as equilibration of urea with brain water and cerebrospinal fluid

Care of the Stroke Patient: Routine Management to Lifesaving Treatment Options

“…Further studies have suggested an additional role in reducing infarct size when used with hypothermia [50] and improved postischemic blood flow in animals pretreated with mannitol [51]. One of the first human studies using mannitol came in 1962 when Drs Wise and Chater [52] demonstrated mannitol as a safe and effective agent to decrease intracranial pressure. In 2003, Bereczki et al [53] performed a prospective observational study of 805 patients reviewing case fatality when mannitol was used in patients admitted within 72 hours of stroke onset.…”

Variation in Osmotic Response to Sustained Mannitol Administration

“…Mannitol, a metabolically inert hexose, is the beststudied osmotic agent, and is typically used first-line for osmotherapy in the United States. It has been consistently shown to reduce intracranial pressure (ICP) (1,2). However, there is currently growing interest in hypertonic saline as an alternative to mannitol (3)(4)(5).…”

“…Even in the presence of a disrupted BBB, an osmotic gradient is still established and mannitol is still able to reduce total brain volume (12,13). Hypertonic mannitol solutions rapidly draw water into the extracellular compartment increasing plasma volume (2), which transiently dilutes extracellular sodium (14)(15)(16). In the kidney, mannitol acts as an osmotic diuretic resulting in the excretion of large volumes of free water (2,17).…”

“…In normal brain with an intact blood-brain-barrier (BBB), however, mannitol is confined to the intravascular compartment; this creates an osmotic gradient, which results in movement of water out of the intracellular and interstitial compartments of the brain into the vasculature. This osmotic effect reduces net intracranial volume and is the most widely accepted mechanism accounting for mannitol's ability to lower ICP (2,(6)(7)(8)(9)(10)(11). Even in the presence of a disrupted BBB, an osmotic gradient is still established and mannitol is still able to reduce total brain volume (12,13).…”

“…Hypertonic mannitol solutions rapidly draw water into the extracellular compartment increasing plasma volume (2), which transiently dilutes extracellular sodium (14)(15)(16). In the kidney, mannitol acts as an osmotic diuretic resulting in the excretion of large volumes of free water (2,17). The overall effect on osmolality depends on the type of intravenous fluids administered.…”