Mannitol exerts its ICP-lowering effects via two mechanisms – An immediate effect because of plasma expansion and a slightly delayed effect related to its osmotic action:
- The early plasma expansion reduces blood viscosity and this in turn improves regional cerebral microvascular flow and oxygenation. It also increases intravascular volume and therefore cardiac output. Together, these effects result in an increase in regional cerebral blood flow and compensatory cerebral vasoconstriction in brain regions where autoregulation is intact, resulting in a reduction in ICP. Cardiac output may subsequently decrease to lower than baseline levels because of the peripheral vasodilatation induced by mannitol and care must be taken to ensure that cerebral perfusion pressure is maintained at this time.
- Mannitol also establishes an osmotic gradient between plasma and brain cells, drawing water from the cerebral extracellular space into the vasculature, thereby reducing cerebral oedema. An intact blood–brain barrier (BBB) is a prerequisite for mannitol’s osmotic action and cerebral oedema may be worsened by mannitol administration if the BBB is disrupted.