There are multiple uses of mannitol which are not FDA-approved.
Mannitol is a six-carbon, linear, simple sugar which is only mildly metabolized by the body and primarily excreted rapidly by the kidneys when given intravenously and poorly absorbed when taken orally.
The FDA-approved indications for mannitol are all for intravenous mannitol and detailed below.
Mannitol for Increased Intracranial Pressure
Mannitol may be used for the reduction of intracranial pressure. In this indication, mannitol administration is intravenous. Mannitol then constitutes a new solute in the plasma, which increases the tonicity of the plasma. Since mannitol cannot cross the intact blood-brain barrier, the increased tonicity from the mannitol draws water out of the brain parenchyma and into the intravascular space. The water then travels with the mannitol to the kidneys where it gets excreted in the urine.
The mannitol causes the cells in the brain to dehydrate mildly. The water inside the brain cells (intracellular water) leaves the cells and enters the bloodstream as the mannitol draws it out of the cells and into the bloodstream. Once in the bloodstream, the extra water is whisked out of the skull. When the mannitol gets to the kidneys, the kidneys filter the mannitol into the urine. The mannitol again draws the water with it, and diuresis (increased urination) ensues.
Mannitol to Reduce Intraocular Pressure
Mannitol may be used to reduce intraocular pressure when given intravenously. The mannitol is a new solute in the intravascular space, which increases the tonicity of the blood plasma. The increased tonicity of the blood plasma draws water out of the vitreous humor of the eye and into the intravascular space. Once in the intravascular space, the mannitol and associate water are excreted by the kidney. The decreased water of the vitreous humor lowers the intraocular pressure.
The mannitol dehydrates the vitreous humor. The mannitol draws water out of the vitreous humor and into the blood vessels as it passes by. When the vitreous humor has less water, after being dehydrated by the mannitol, it has less mass and thus creates less pressure. The lower pressure is less likely to damage the retina. The mannitol remains in the blood vessels and is excreted, with its associated water, into the urine.
Mannitol to Promote Diuresis in Acute Renal Failure
Mannitol can be used in acute renal failure to help prevent or treat the oliguric phase. During the oliguric phase urine output decreases to less than 0.5 mg/kg/hour for children and less than 400 mL/day in adults. The fluid which does not get excreted remains in the body and cause fluid overload. Fluid overload causes issues such as decreased oxygenation and ventilation, electrolyte abnormalities, swelling, encephalopathy, and cardiac arrest. An individual with acute renal failure can sometimes be giving intravenous mannitol. Even during acute renal failure, much of mannitol excretion is by the kidneys. As the mannitol gets excreted, it draws water with it, which can increase the water excretion of the patient and help avoid or treat the fluid overload caused by oliguria in acute renal failure. However, Mannitol causes significant osmotic injury to tubules leading to ATN(acute tubular necrosis) so its use for this indication is almost obsolete.
Mannitol to Excrete Toxic Materials
Much like mannitol given for oliguria of acute renal failure, mannitol can be given to increase the excretion of toxic materials, substances, and drugs. The kidneys excrete mannitol. The mannitol is poorly reabsorbed once excreted and thus draws extra water with it into the renal collecting ducts. The extra water in the renal collecting ducts can help increase the excretion of water-soluble toxic materials, substances, and drugs.
Mannitol to Prevent Intradialytic Hypotension
Intradialytic hypotension and dialysis disequilibrium symptoms are common in hemodialysis patients. This is due to a drop in intradialytic osmolality. Mannitol can be used to prevent intradialytic hypotension by raising serum osmolality.
Additional Mechanisms of Action
Since mannitol is a sugar and it provides a sweet taste when ingested orally. Mannitol also mostly passes through the intestine and is excreted in the feces as the small intestine absorbs it poorly. Thus, mannitol is used as a sweetener in food for diabetic patients as mannitol can provide sweetness to the food without increasing the blood sugar as much as sucrose.
When using mannitol for medical purposes, it is given intravenously. Mannitol can be found in varying concentrations from 5% mannitol (5 gm mannitol dissolved in 100 mL of fluid) up to 25% mannitol (25 gm of mannitol dissolved in 100 mL of fluid). A commonly encountered solution is 20% mannitol (20 grams of mannitol dissolved in 100 mL of fluid).
There are multiple adverse effects which mannitol can cause including:
There are multiple contraindications to giving mannitol, including:
When giving mannitol, it is essential to monitor cardiac function as the fluid shifts can precipitate heart failure. Additional electrolytes, including sodium, potassium, and osmolality, all require monitoring. The clinician should stop mannitol if significant electrolyte abnormalities develop or the osmolality reaches 320 mOsm or higher. Finally, urine output also requires monitoring; failure for urine output to increase after administration of mannitol should prompt cessation of mannitol and evaluation for possible renal or genitourinary issues.
Dialysis partially removes mannitol. Repeated doses of mannitol lead to the build-up of mannitol even with dialysis.
A multidisciplinary team approach is an optimal approach with mannitol administration. It is essential to monitor cardiac function as the fluid shifts can precipitate heart failure. Additional electrolytes, including sodium, potassium, and osmolality, require monitoring by the nurses and physicians. Abnormalities in these laboratory values necessitate prompt communication to all members of the team. Mannitol administration should stop if significant electrolyte abnormalities develop or the osmolality reaches 320 mOsm or higher. When mannitol is used to treat cerebral edema, serum osmolality should be checked every 4 to 6 hours. If serum osmolality is more than 320 mOsm, alternative agents like the hypertonic solution should be used.
The nursing staff should pay particular attention to urine output and monitor it carefully, reporting any concerns to the treating physician. The pharmacist can verify dosing and perform medication reconciliation and alert the team if any interactions are present. They can also collaborate with the treating physician regarding potential alternative therapies in the event of therapeutic failure or intolerance of mannitol. Only with open interprofessional communication between all members of the healthcare team can any therapy, including mannitol, have the best chance at optimal results. [Level V]
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