Mannitol was introduced into clinical use in 1961 1).

Despite widespread use of a number of osmolar agents (mannitol, urea, and glycerol) up until the late 1970s 2) 3), mannitol gradually became the agent of choice to manage ICP 4).

(also referred to as mannite or manna sugar) is a white, crystalline solid with the chemical formula C6H8(OH)6. It was originally isolated from the secretions of the flowering ash and called manna after its resemblance to the Biblical food. In plants, it is used to induce osmotic stress. It has several industrial uses, but is mainly used to produce tablets of medicine. Its fetal safety is “C” in Briggs' Reference Guide to Fetal and Neonatal Risk.

Mannitol is classified as a sugar alcohol; that is, it is derived from a sugar (mannose) by reduction. Other sugar alcohols include xylitol and sorbitol. Mannitol and sorbitol are isomers, the only difference being the orientation of the hydroxyl group on carbon 2.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Among the various osmotic agents available for administration to treat cerebral edema, mannitol (administered rapidly in a 1 gm/kg bolus) has been the most commonly selected medication in the neurointensive care setting 5).

However, mannitol may lead to systemic hypotension, decreased cerebral perfusion, acute renal failure, and delayed accumulation within the extravascular compartment that leads to a paradoxical rebound elevation in intracranial pressure 6) 7).

Elliot et al. analyzed mannitol dosing errors at peripheral hospitals prior to or during transport to tertiary care facilities for intracranial emergencies. They also investigated the appropriateness of mannitol use based on the 2007 Brain Trauma Foundation guidelines for severe traumatic brain injury.

The authors conducted a retrospective review of the Shock Trauma Air Rescue Society (STARS) electronic patient database of helicopter medical evacuations in Alberta, Canada, between 2004 and 2012, limited to patients receiving mannitol before transfer. They extracted data on mannitol administration and patient characteristics, including diagnosis, mechanism, Glasgow Coma Scale score, weight, age, and pupil status.

A total of 120 patients with an intracranial emergency received a mannitol infusion initiated at a peripheral hospital (median Glasgow Coma Scale score 6; range 3-13). Overall, there was a 22% dosing error rate, which comprised an underdosing rate (< 0.25 g/kg) of 8.3% (10 of 120 patients), an overdosing rate (> 1.5 g/kg) of 7.5% (9 of 120), and a nonbolus administration rate (> 1 hour) of 6.7% (8 of 120). Overall, 72% of patients had a clear indication to receive mannitol as defined by meeting at least one of the following criteria based on Brain Trauma Foundation guidelines: neurological deterioration (11%), severe traumatic brain injury (69%), or pupillary abnormality (25%).

Mannitol administration at peripheral hospitals is prone to dosing error. Strategies such as a pretransport checklist may mitigate this risk 8).

Intraoperative Mannitol.

Mannitol in severe traumatic brain injury

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2) , 4)
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Elliott CA, MacKenzie M, O'Kelly CJ. Mannitol dosing error during interfacility transfer for intracranial emergencies. J Neurosurg. 2015 Jun 16:1-4. [Epub ahead of print] PubMed PMID: 26077141.
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