The Use of Mannitol in Acute Traumatic Brain Injury

Mannitol has been widely used to reduce intracranial pressure (ICP) as early as the 1960s, classically thought to be due to its hyperosmotic action to draw water from the edematous brain. This osmotic property usually takes effect in 15-30 minutes when it sets up an osmotic gradient and draws water out of neurons.

However, it was subsequently shown that there was actually less correlation between changes in ICP with changes with white matter water content (see this review article, which was written in an easy to understand way).

Severe other mechanisms were proposed to explain away how mannitol works.
One of them is the change in cerebral hemodynamics induced by mannitol. Mannitol has been proven to increase cerebral perfusion pressure (CPP) and microcirculation perfusion.

Therefore, many proposed that the primary effect of mannitol may be due to its ability to improve the rheology and thus, the reduction in viscosity.

This leads to increased flow, increased in CBF and cerebral O2 delivery.

The brain intact auto regulatory mechanism (like a loop of negative feedback) then results in vasoconstriction which decrease cerebral blood volume and lowers ICP.

Mannitol is not without disadvantages. Two notorious disadvantages:

1/ Prolonged use (continuous infusion) of mannitol molecules results in the movement of the mannitol molecules across the post-traumatic leaky blood brain barrier into the cerebral interstitial space and may thus, paradoxically, exacerbate cerebral oedema and raise ICP. Mannitol itself can directly contributes to this breakdown of the blood brain barrier.

2/ Mannitol, through its osmotic diuresis action, not only reduce ICP but may reduce intravascular volume, thereby compromising cerebral perfusion pressure, which could have a deleterious effect on outcomes for brain-injured patients.

In such cases where the blood pressure is low (e.g. hypovolemic shock), an alternative would be to use hypertonic saline. Hypertonic Saline has been shown to be a viable alternative option. The ICP reduction was sustained for at least 24 hours without repeat saline administration.

A Cochrane Review has been published regarding the role of Mannitol in Acute Traumatic Brain Injury. Click here to access.


In short, some of the salient points of the Cochrane review includes:
- At the current moment, the effectiveness of mannitol in the ongoing treatment of severe head injury remains unclear.

- There is evidence that excessive administration of mannitol may be harmful, by mannitol passing from the bloodstream into the brain, increases the ICP and worsens the cerebral edema.

- This review found a small benefit when mannitol treatment is directed by measurement of intracranial pressure compared to ‘standard treatment' (treatment without measurement of intracranial pressure).

- However, when compared to treatment with hypertonic saline, it was found that treatment with mannitol may increase the likelihood of death.

- The review found insufficient data on the effectiveness of pre-hospital administration of mannitol at the current moment.