Mannitol is the only osmotic diuretic in current use. Structurally, mannitol is a six-carbon sugar alcohol that does not undergo metabolism.

1. Pharmacokinetics and Pharmacodynamics. After administration, mannitol is completely filtered at the glomeruli, and none of the filtered drug is subsequently reabsorbed from the renal tubules. By increasing tubular fluid osmolality, it decreases water reabsorption and promotes water diuresis.

2. Clinical Uses

   1. Mannitol is used primarily in the acute management of elevated intracranial pressure and in the treatment of glaucoma. Mannitol decreases intracranial pressure by increasing plasma osmolarity, which draws water from tissues, including the brain, along an osmotic gradient. Mannitol begins to exert an effect within 10 to 15 minutes, with a peak effect at 30 to 45 minutes and a duration of 6 hours. An intact blood-brain barrier is necessary for the cerebral effects of mannitol. If the blood-brain barrier is not intact, mannitol may enter the brain, drawing fluid with it and causing worsening of the cerebral edema. In addition, a rebound increase in intracranial pressure may occur following mannitol use.

   2. Mannitol has been used to prevent perioperative kidney failure in the setting of acute tubular necrosis.

   3. Mannitol also has free radical scavenging properties, which may protect transplanted kidneys following reperfusion.

   4. Despite its common use during cardiac and major vascular surgery for renal protection, it has not been shown to prevent perioperative acute renal failure.

3. Side Effects

   1. The initial increase in intravascular volume associated with the administration of mannitol may be poorly tolerated in patients with left ventricular dysfunction, leading to pulmonary edema (furosemide may be a preferred drug for treatment of increased intracranial pressure in patients with left ventricular dysfunction).

   2. Prolonged use of mannitol may cause hypovolemia, electrolyte disturbances with hypokalemic hypochloremic alkalosis, and plasma hyperosmolarity due to excessive excretion of water and sodium.