Mannitol: a review of its clinical uses

Abstract

Mannitol, chemically 1,2,3,4,5,6-hexanehexol (C6H8(OH)6), is a polyol (sugar alcohol) which is widely used in the food and pharmaceutical industries because of its unique functional properties (Fig. 1). In particular, it is about half as sweet as sucrose and, when taken orally, has a cooling effect which is considered desirable in masking bitter tastes. It is a naturally occurring substance found in marine algae, fresh mushrooms, and in the exudates from trees. It is an isomer of sorbitol, which is usually synthesized by the hydrogenation of specialty glucose syrups. Mannitol is available commercially in a variety of white crystalline powder and granular forms, all of which are soluble in water. In addition to its use in the food and pharmaceutical industries, mannitol is also widely used in medical practice for a variety of indications (Table 1), primarily because of its osmotic properties (see below). For clinical use, it is supplied as sterile solutions of 10% and 20% in a 500 ml bag of water containing 50 and 100 g of mannitol, respectively. Mannitol solutions are acidic (pH 6.3) but proprietary preparations have sodium bicarbonate added for pH adjustment. Mannitol may crystallize if stored at room temperature but can be made soluble again by warming the solution. Because of its low molecular weight (182), mannitol is freely filtered through the renal tubules. However, as it is not reabsorbed, it continues to be osmotically active in the tubules and this accounts for its action as an osmotic diuretic. Mannitol also causes release of renal prostaglandins that lead to renal vasodilation and an increase in tubular urine flow that is believed to protect against renal injury by reducing tubular obstruction. It also acts as a free-radical scavenger and reduces the harmful effects of free radicals during ischaemia–reperfusion injury. The relevant actions of mannitol in specific clinical scenarios are discussed in more detail below. Mannitol has many side-effects including initial volume expansion (increasing the risk of heart failure), subsequent hypovolaemia and hypotension, metabolic acidosis, and electrolyte imbalance, including hypernatraemia and hypokalaemia. In large doses, it can also cause renal failure because of intra-renal vasoconstriction and intravascular volume depletion. Repeated administration may result in unacceptably high serum osmolality (.320 mOsm litre) and subsequent neurological complications. A comprehensive list of side-effects is given in Table 2.