Mannitol

Mannitol or hexan-1,2,3,4,5,6-hexol (C₆H₈(OH)₆) is an osmotic diuretic agent and a weak renal vasodilator. It is a sorbitol stereoisomer.

It was originally isolated from the secretions of the Flowering Ash, called Manna after their resemblance to the Biblical food, and may also be referred to as Mannite and Manna Sugar.^[1]

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Chemical properties

Chemically, mannitol is a sugar alcohol, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate.

Uses

Mannitol is used clinically to reduce acutely raised intracranial pressure, until more definitive treatment can be given, e.g. after head trauma (although significant controversy exists over this use), and to treat patients with oliguric renal failure. It is administered intravenously, and is filtered by the glomerulus of the kidney, but is incapable of being reabsorbed from the renal tubule, resulting in decreased water and Na⁺ reabsorption via its osmotic effect. Consequently, mannitol increases water and Na⁺ excretion, thereby decreasing extracellular fluid volume.

Mannitol can also be used to open the blood-brain barrier by temporarily shrinking the tightly coupled endothelial cells that make up the barrier. This makes mannitol indispensable for delivering various drugs directly to the brain (e.g. in the treatment of Alzheimer's disease).

Mannitol is also used as a sweetener for people with diabetes. Since mannitol has a negative heat of solution, it is used as a sweetener in "breath-freshening" candies, the cooling effect adding to the fresh feel. In doses larger than 20g, mannitol acts as a laxative, and is sometimes sold as a laxative for children.

It is sometimes used as an adulterant or cutting agent for heroin, methamphetamines or other illicit drugs. In popular culture, when it is used in this manner, it is often referred to as baby laxative. Many television shows and films depicting drug culture make references to baby laxative.

Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an artificial pacemaker) while it is passing through the venous system. Because it dissolves readily in blood, the sharp point will become exposed by the time it reaches its destination.

Mannitol may be administered in cases of severe Ciguatera poisoning. Severe ciguatoxin, or "tropical fish poisoning" can produce stroke-like symptoms.

Mannitol is a non-permeating molecule; i.e., it cannot cross biological membranes.

Mannitol is commonly used in the circuit prime of a heart lung machine during cardiopulmonary bypass (CPB). The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass. The solution prevents the swelling of endothelial cells in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage.

Mannitol is also being developed by an Australian pharmaceutical company as a treatment for cystic fibrosis and bronchiectasis and as a diagnostic test for airway hyperresponsiveness. The mannitol is orally inhaled as a dry powder through what is known as an osmohaler. The critical component of the mannitol being the particle size distribution (PSD). The company has marketing approval for its diagnostic in Australia and Europe and is currently applying for approval from the FDA.

Chemical Abstract Registry Numbers for Mannitol are

• 123897-58-5
• 69-65-8
• 75398-80-0
• 85085-15-0

Controversy

The three studies^[2][3][4] which initially found that mannitol was effective in cases of severe head injury have been the subject of a recent investigation.^[5] Although several authors are listed, the others had no knowledge of how, where, or even if the patients were recruited, meaning that the papers were essentially conducted by Dr. Cruz, who killed himself in 2005. Further, the Federal University of São Paulo, which he gave as his affiliation, has never employed him. Currently, therefore, the Cochrane review recommending mannitol^[6] has been withdrawn pending re-evaluation, as there is some evidence that mannitol may worsen cerebral oedema.^[7]

References

1. ^ Cooley's Cyclopaedia of Practical Receipts, 6th ed. (1880)
2. ^ Cruz J, Minoja G, Okuchi K. Improving clinical outcomes from acute subdural hematomas with the emergency preoperative administration of high doses of mannitol: a randomized trial. Neurosurgery. 2001 Oct;49(4):864-71. PMID 11564247
3. ^ Cruz J, Minoja G, Okuchi K. Major clinical and physiological benefits of early high doses of mannitol for intraparenchymal temporal lobe hemorrhages with abnormal pupillary widening: a randomized trial. Neurosurgery. 2002 Sep;51(3):628-37; discussion 637-8. PMID 12188940
4. ^ Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 2004 Mar;100(3):376-83. PMID 15035271
5. ^ Roberts I, Smith R, Evans S. Doubts over head injury studies. BMJ. 2007 Feb 24;334(7590):392-4. PMID 17322250
6. ^ Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001049. PMID 16235278
7. ^ Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992 Oct;77(4):584-9. PMID 1527619

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