Complications of mannitol therapy
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor Emeritus
- University of Rochester School of Medicine and Dentistry
Mannitol, given as a hypertonic solution, is primarily used in the treatment of cerebral edema and glaucoma. Although generally well tolerated, a variety of fluid, electrolyte, and renal complications can occur if the patient is not carefully monitored. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Mannitol' and "Angle-closure glaucoma", section on 'Treatment'.)
Volume depletion and hypernatremia — Mannitol is freely filtered by the glomerulus and does not undergo tubular reabsorption. Thus, it acts as an osmotic diuretic, increasing urinary losses of both sodium and electrolyte-free water. Lack of replacement of the fluid losses can lead to both volume depletion and hypernatremia that can be severe .
Volume expansion, hyponatremia, hyperkalemia, hypokalemia, and metabolic acidosis — If very high doses of hypertonic mannitol are infused, or if the drug is given to patients with preexisting renal failure, mannitol is retained in the circulation [2-4]. The ensuing rise in plasma osmolality, similar to that produced by hyperglycemia, results in the osmotic movement of water and potassium out of cells leading to extracellular fluid volume expansion (and possibly pulmonary edema), hyponatremia, metabolic acidosis (by dilution), and hyperkalemia [5,6]. Water losses from brain cells cause neurologic symptoms. Volume expansion and dilutional hyponatremia, without neurologic symptoms, can also be induced when isotonic mannitol is used as a flushing solution during transurethral resection of the prostate or bladder. (See "Hyponatremia following transurethral resection or hysteroscopy".)
The rise in the plasma potassium concentration following hypertonic mannitol is due to the movement of potassium out of the cells into the extracellular fluid via two mechanisms : (1) the rise in cell potassium concentration induced by water loss favors passive potassium exit through potassium channels in the cell membrane; and (2) the frictional forces between solvent (water) and solute can result in potassium being carried out through the water pores in the cell membrane (a process that is called solvent drag). A similar process can occur with acute hypernatremia  and also largely accounts for the hyperkalemia that is commonly seen with marked hyperglycemia in uncontrolled diabetes mellitus [8,9]. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis".)
If kidney function is normal, the transient shift of potassium out of cells due to mannitol seldom leads to hyperkalemia. A study of 45 patients treated for several days with mannitol (average dose, 28 g every six hours) for neurosurgical conditions found only one patient (2.4 percent) with a serum potassium above 5.5 meq/L on the first day, and no patients with hyperkalemia on subsequent days . By contrast, 22 percent of patients developed hypokalemia (serum potassium <3.5 meq/L) on the first day, and this proportion increased to 52 percent by the third day.
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