In conjunction with adequate replacement of water and electrolytes and maintenance of normal blood pressure, mannitol is used to promote diuresis for the prevention and/or treatment of the oliguric phase of acute renal failure which may occur after massive hemorrhage, trauma, shock, burns, transfusion reactions caused by mismatched blood, or major surgery. The drug may prevent or reverse acute functional renal failure before there is evidence of tubular necrosis or multiple vascular thrombosis; however, mannitol has no effect and may be harmful if used after tubular necrosis and irreversible renal failure become established.
Mannitol has been used during cardiovascular surgical procedures, including open heart surgery and surgery to correct aortic aneurysms. Use of the drug may prevent hemoglobin buildup during cardiopulmonary bypass procedures. Mannitol has been used to protect renal function in patients with poor renal function undergoing various surgical procedures such as nephrolithotomy or renal artery surgery; however, the drug does not permit prolonging the time of occlusion and renal ischemia during renovascular reconstructive surgery. The drug has also been recommended for use during abdominal surgery or other major surgery, especially in jaundiced patients who appear to be particularly susceptible to postoperative renal failure. In one study, mannitol prevented azotemia, but not systemic acidosis, caused by amphotericin B in 4 patients being treated for systemic fungal infections following kidney transplantation.
Reduction of Intracranial Pressure
Mannitol is used prior to and during neurosurgery to reduce greatly increased intracranial pressure and for the treatment of cerebral edema. The drug is especially indicated when there is evidence of herniation and developing brainstem compression. A rebound increase in intracranial pressure may occur approximately 12 hours after osmotic diuresis is employed; however, this occurs less frequently with mannitol than with urea. Mannitol is also useful for the early treatment of cerebral edema in patients with diabetic ketoacidosis or in patients in hypoglycemic coma who fail to respond to increases in blood glucose concentrations. Mannitol has also been used to reduce edema in the traumatized area of the spinal cord prior to corrective surgery.
Reduction of Intraocular Pressure
Mannitol is used to reduce elevated intraocular pressure when the pressure cannot be lowered by other means. The drug is especially useful for treating acute episodes of angle-closure, absolute, or secondary glaucoma and for lowering intraocular pressure prior to intraocular surgery. Mannitol may be of value in those cases of cataract extraction in which vitreous loss is likely. Unlike urea, mannitol does not penetrate the eye and may be used when irritation is present.
Mannitol is used alone or with other diuretics such as furosemide or ethacrynic acid to promote the urinary excretion of toxins such as aspirin or other salicylates, some barbiturates, bromides, or imipramine as an adjunct to usual treatment regimens in patients with severe intoxications. Continuous infusion of mannitol in some cases of drug poisoning has reduced the period of unconsciousness and maintained urine flow. Renal lesions caused by inhalation or ingestion of carbon tetrachloride may possibly be prevented by early treatment with mannitol. Unlike many other diuretics, mannitol increases the urinary excretion of lithium and may be useful for the treatment of lithium intoxication. The drug has also been used to promote excretion of uric acid and prevent hyperuricemia and/or uric acid nephropathy in patients who develop uricemia following chemotherapy or radiation therapy for leukemia or lymphoma. Concomitant administration of sodium bicarbonate may be needed to alkalinize the urine in the treatment of salicylate or barbiturate poisonings or uricemia. Mannitol has also been found useful in treating carbon monoxide poisoning and ethylene glycol intoxication.
There is limited evidence that mannitol may be useful in the management of ciguatera fish poisoning, but additional study and experience are necessary.102 Although the mechanism(s) of action is not known, the drug appeared to reverse neurologic and neurosensory manifestations of such poisoning as well as GI manifestations in a limited number of patients.102 No specific antidote for ciguatera fish poisoning has been identified to date, and treatment remains supportive and symptomatic; therefore, pending further accumulation of data, some clinicians suggest that use of mannitol (e.g., 1 g/kg by IV infusion) be considered for initial therapy, combined with other supportive therapy as necessary, in patients with clinically important manifestations of such poisoning.102
Mannitol has been used alone or in conjunction with other diuretics to promote diuresis for the supportive treatment of edema and ascites of nephrotic, cirrhotic, or cardiac origin. The drug may also be useful to relieve the symptoms and congestion of pulmonary edema caused by bronchopneumonia. Mannitol may be indicated when thiazides or other diuretics that act by inhibiting transport mechanisms fail because of decreased glomerular filtration rate caused by shock, dehydration, or trauma or when further depression of renal function produced by other diuretics is contraindicated. However, mannitol diuresis offers only symptomatic relief of edema and is independent of and has no effect on the underlying disease process. IV therapy with mannitol is impractical for the treatment of chronic edema. Use of the drug requires larger volumes of fluid to be administered than do other osmotic diuretics; however, unlike dextrose, it is not contraindicated for use in diabetic patients and it causes less local irritation and necrosis than does urea.
Mannitol is also used as an irrigating solution in transurethral prostatic resection. Use of the drug minimizes the hemolytic effects of water, the entrance of hemolyzed blood into the circulation, and the resulting hemoglobinemia which is considered a major factor in producing serious renal complications. In addition, mannitol has been administered IV before, during and after transurethral prostatectomy to maintain urine output, promote rapid excretion of absorbed irrigants, and reduce the need for postoperative irrigation.
Mannitol has been administered by intra-amniotic instillation in attempts to terminate pregnancy; however, the drug has been reported to have a high failure rate and therefore to be unreliable for this purpose.
For the use of mannitol to measure glomerular filtration rate, see Mannitol 36:40.
Mannitol injections are administered by IV infusion. An administration set with a filter should be used for infusion of injections containing 20% or more, since mannitol crystals may be present. For transurethral prostatic resection, mannitol irrigation solutions are instilled into the bladder via an indwelling urethral catheter.
The dosage, concentration of solution, and rate of administration of mannitol vary with the condition being treated and the patient's fluid requirements, urinary output, and response to the drug.
Patients with marked oliguria or suspected inadequate renal function should receive a dose of about 0.2 g/kg or 12.5 g as a 15 or 20% solution infused over a period of 3-5 minutes to test renal response before mannitol therapy is initiated. A response is considered adequate if at least 30-50 mL of urine per hour is excreted over the next 2-3 hours. If an adequate response is not attained, a second test dose may be given. If a satisfactory response is not obtained after the second test dose, the patient should be reevaluated and mannitol should not be used.
For the prevention of oliguria or acute renal failure, 50-100 g of mannitol may be given. Generally, a concentrated solution of the drug is given initially followed by a 5 or 10% solution. When used prophylactically in surgical procedures, administration of the drug may be initiated before or immediately following surgery and may be continued postoperatively. When mannitol was used to reduce nephrotoxicity caused by amphotericin B, 12.5 g of mannitol was administered immediately before and after each dose of amphotericin B. For the treatment of oliguria, 100 g of mannitol is usually given as a 15 or 20% solution over 90 minutes to several hours.
Reduction of Intracranial or Intraocular Pressure
To reduce intracranial pressure and brain mass, and to lower elevated intraocular pressure, the usual dose of mannitol is 1.5-2 g/kg administered as a 15, 20, or 25% solution over a period of 30-60 minutes. Some clinicians have recommended as little as 1 g or as much as 3.2 g/kg to lower intraocular pressure. When used preoperatively, the drug should be administered 1-1.5 hours prior to surgery in order to achieve maximum reduction of pressure before surgery.
To promote diuresis in the adjunctive treatment of severe drug intoxications, various mannitol regimens have been used. In general, a urinary output of at least 100 mL/hour, but preferably 500 mL/hour, and a positive fluid balance of 1-2 L should be maintained. Some clinicians recommend an initial loading dose of 25 g, followed by infusion of a solution at a rate that will maintain a urinary output of at least 100 mL/hour. In barbiturate poisoning, an initial dose of 0.5 g/kg, followed by administration of a 5 or 10% solution at a rate to maintain the desired urine output, has been recommended. Alternatively, it has been recommended that 1 L of a 10% solution be given during the first hour. Urine volume and pH should be measured and cumulative fluid balance calculated at the end of the first hour and subsequent 2-hour periods. If positive fluid balance remains at 1-2 L, another liter of 10% mannitol may be given over the next 2 hours. If positive fluid balance falls below 1 L, mannitol should be replaced with 1 L of (1/6) M sodium lactate over the next 2 hours (if urine pH is less than 7) or 1 L of 0.9% sodium chloride over 2 hours (if urine pH is greater than 7). If the positive fluid balance is more than 2 L, 10% mannitol may be given at the slowest possible rate. IV administration of furosemide was recommended if the positive fluid balance exceeded 2.5 L. For the treatment of uricemia, 50 g/m2 has been given in 24 hours.
As a diuretic for the adjunctive treatment of edema and ascites, 100 g of mannitol may be infused as a 10-20% solution over a period of 2-6 hours.
Transurethral Prostatic Resection
Solutions containing 2.5-5% mannitol are used as irrigating solutions in transurethral prostatic resection. One limited study indicates that mannitol concentrations of at least 3.5% are necessary to prevent hemolysis.
Mannitol dosage requirements for patients 12 years of age and younger have not been established. However, some clinicians have suggested the following dosages for pediatric patients. In oliguria or anuria, a test dose of 0.2 g/kg or 6 g/m2 may be given as a single dose over 3-5 minutes. For therapeutic purposes, 2 g/kg or 60 g/m2 may be given. For the treatment of edema and ascites, this dose may be given as a 15 or 20% solution over 2-6 hours. To reduce cerebral or ocular edema, the dose may be given as a 15 or 20% solution over 30-60 minutes. For the treatment of intoxications, the drug may be given as a 5 or 10% solution as needed.
Effects on Fluids and Electrolytes
The most severe adverse effects encountered during mannitol therapy are fluid and electrolyte imbalance. Accumulation of mannitol caused by inadequate urinary output or to rapid administration of large doses may result in overexpansion of extracellular fluid. The resulting circulatory overload may result in pulmonary edema, signs and symptoms of water intoxication, and fulminating congestive heart failure, especially in patients with diminished cardiac reserve. Overhydration may be corrected by hemodialysis or administration of a potent diuretic (e.g., furosemide).
Electrolyte imbalance, in some cases severe enough to alter acid-base balance or depress respiration, may result from mannitol-induced diuresis. Hyponatremia or hypernatremia and hypokalemia or hyperkalemia may occur. The shift of sodium-free intracellular fluid into extracellular spaces may result in dilutional lowering of serum sodium concentrations and may cause hyponatremia or aggravate preexisting hyponatremia. Hyponatremia may be accompanied by tremor or seizures and may result in death. Loss of water in excess of sodium, as may occur during prolonged therapy with mannitol, may result in hypernatremia and hyperosmolality. A natriuretic agent such as a thiazide may be administered concomitantly if this occurs.
Symptoms of CNS toxicity have occurred in 3 patients with acute renal failure who received 25 g of mannitol every 12 hours for at least 36 hours. When large doses of mannitol are administered, especially in the presence of acidosis, the drug may cross the blood-brain barrier and interfere with the ability of the brain to maintain CSF pH. Cerebral dessication may also occur, and the mechanisms that protect the brain from the effects of systemic acidosis may be disrupted. CNS damage may result, and death has occurred in patients with organic CNS disease who received mannitol.
Other adverse effects that have occurred during mannitol therapy include acidosis, dryness of the mouth, thirst, urinary retention, headache, blurred vision, uricosuria, nausea, vomiting, rhinitis, arm pain, backache, thrombophlebitis, chills, dizziness, urticaria, hypotension, hypertension, tachycardia, fever, transient muscle rigidity, and angina-like chest pain.
Vacuolar nephrosis, possibly irreversible, has occurred during administration of mannitol. Reversible, acute oligoanuric renal failure has occurred in several patients with normal pretreatment renal function who received large IV dosages (400-900 g daily) of mannitol for the reduction of intracranial100 or intraocular101 pressure; the mechanism of this effect has not been fully elucidated.100, 101 Urine output and glomerular filtration rate declined abruptly in these patients but returned toward or exceeded normal within several days after discontinuance of mannitol;100 one patient underwent ultrafiltration and hemodialysis.101
Extravasation of mannitol should be avoided, since local edema and skin necrosis may result. In a patient with a history of allergies, mannitol caused a severe allergic reaction and anaphylaxis which responded to treatment with epinephrine hydrochloride. Intraocular hemorrhage has also occurred but could not be definitely attributed to mannitol.
Precautions and Contraindications
Mannitol should not be administered until the adequacy of the patient's renal function and urine flow has been established. A test dose may be employed for this purpose. (See Dosage and Administration: Dosage.) In patients with shock with oliguria and rising BUN, mannitol should not be administered until fluids, plasma, blood, and electrolytes have been replaced. The cardiovascular status of the patient should also be carefully evaluated prior to mannitol administration.
Renal function, urine output, fluid balance, serum sodium and potassium concentrations, and central venous pressure should be monitored during mannitol administration. If urine output continues to decline, the patient's clinical status should be reviewed and mannitol discontinued if necessary. If central venous pressure rises or there is any other evidence of circulatory overload, the infusion should be slowed or stopped. Fluid administration should not exceed 1 L/day in excess of urinary output. The sustained diuresis caused by mannitol may obscure and intensify inadequate hydration or hypovolemia. Tissue dehydration may occur, especially when urine output is less than 40 mL/minute, and may lead to coma. Hypovolemia reduces glomerular filtration rate and enhances the reabsorption of sodium and water, thus promoting oliguria. In addition, preexisting hemoconcentration may be intensified.
Mannitol is not a substitute for fluid and electrolyte therapy, and homeostasis should be maintained by hydration and electrolyte therapy. Volume and electrolyte depletion may be prevented or treated by administering dilute mannitol solutions with sodium chloride added or by alternating each liter of mannitol solution with a liter of sodium chloride injection to which 40 mEq of potassium chloride has been added. If the threat of renal shutdown exists, potassium supplementation should be administered subsequent to, but not concomitantly with, mannitol.
Mannitol is contraindicated in patients with well established anuria caused by severe renal disease or impaired renal function who do not respond to a test dose. (See Dosage and Administration: Dosage.) The drug is also contraindicated in patients with severe pulmonary congestion, frank pulmonary edema, severe congestive heart disease, severe dehydration, metabolic edema associated with capillary fragility or membrane permeability and not due to renal, cardiac or hepatic disease, or active intracranial bleeding except during craniotomy. Mannitol is contraindicated for further use when progressive renal disease or dysfunction, including increasing oliguria and azotemia, or progressive heart failure or pulmonary congestion occur after institution of mannitol therapy. Electrolyte-free mannitol solutions should not be given concomitantly with blood. If blood must be given simultaneously with mannitol, at least 20 mEq of sodium chloride should be added to each liter of mannitol solution to avoid pseudoagglutination.
Animal reproduction studies have not been performed with mannitol. It is also not known whether mannitol can caused fetal harm when administered to pregnant women. Mannitol should be used during pregnancy only when clearly needed.
It is not known whether mannitol affects fertility in humans.
Because mannitol increases urinary excretion of lithium, patients being treated with lithium should be observed for possible impairment of response to that drug if they receive mannitol.
In addition to alterations in laboratory test values resulting from mannitol-induced electrolyte changes, the drug may affect the results of other tests. Determinations of inorganic phosphorus blood concentrations are interfered with by use of the drug; values may be increased or decreased. Mannitol will also interfere with laboratory determinations of blood ethylene glycol concentrations, because both substances are oxidized to an aldehyde during the test procedure.
IV administration of mannitol induces diuresis mainly by elevating the osmotic pressure of the glomerular filtrate to such an extent that the tubular reabsorption of water and solutes is hindered. For mannitol to be effective, enough renal blood flow and glomerular filtration must exist to enable the drug to reach the tubules. Increased renal blood flow resulting from dilation of vascular segments between the renal artery and glomeruli, lowered renal vascular resistance, and reduced blood viscosity may also contribute to the diuretic effect of the drug. Mannitol promotes the excretion of sodium; however, proportionately more water than sodium is excreted. Excretion of potassium, chloride, calcium, phosphorus, lithium, magnesium, urea, and uric acid is also increased during mannitol-induced diuresis. The drug protects the kidneys from nephrotoxins by preventing toxins from becoming concentrated in the tubular fluid.
Mannitol may prevent or reverse acute functional renal failure by reversing the acute reductions in renal blood flow, glomerular filtration rate, urine flow, and sodium excretion which may occur after trauma. However, the drug must exert its effect before decreases in filtration rate and renal blood flow produce tubular damage, interstitial edema, and/or diffuse ischemia.
The osmotic effect of mannitol causes water to be drawn from cells to extracellular fluid and from erythrocytes cells to plasma. As a result, extracellular fluid volume, plasma volume, and circulation time are increased and extracellular stores of sodium are diluted. Cellular dehydration may result. Plasma pH is decreased. Erythrocyte volume becomes more concentrated and hematocrit is decreased. The fluid shifts caused by the drug result in reduction of cerebral edema by a reduction in brain mass and in the lowering of elevated CSF pressure. However, a rebound increase in intracranial pressure may occur approximately 12 hours after the administration of mannitol. Fluids are also withdrawn from the anterior chamber of the eye, resulting in a reduction of elevated intraocular pressure.
When administered orally, mannitol causes profound osmotic diarrhea, resulting in a loss of fluid, sodium, and potassium. Serum sodium concentrations are increased, but serum potassium and blood urea concentrations are reduced.
Although mannitol has been thought not to be absorbed when administered orally, one study revealed that about 17% of an oral dose of radiolabeled drug was excreted unchanged in urine.
Diuresis may occur within 1-3 hours after IV administration of mannitol. Lowering of elevated intraocular pressure occurs within 30-60 minutes and persists for 4-6 hours. Elevated CSF pressure may be reduced within 15 minutes after starting an infusion of mannitol, and the effect may last for 3-8 hours after the infusion is stopped.
When administered IV, mannitol remains confined to the extracellular compartment. The drug does not cross the blood-brain barrier unless very high concentrations are present in the plasma or the patient has acidosis. Unlike urea, mannitol does not penetrate the eye.
Mannitol is metabolized only very slightly, if at all, to glycogen in the liver. The drug is freely filtered by the glomeruli, with less than 10% tubular reabsorption; it is not secreted by tubular cells. The elimination half-life in adults is about 100 minutes. Approximately 80% of a 100-g dose is excreted unchanged in urine within 3 hours. When large dose are given as in forced diuresis, retention of the drug may occur. In the presence of renal disease in which glomerular function is impaired or in conditions that impair small vessel circulation, such as congestive heart failure, cirrhosis with ascitic accumulation, shock, or dehydration, mannitol clearance is lower than normal.
Mannitol, a hexahydroxy alcohol chemically related to mannose, is an osmotic diuretic. Mannitol occurs as a white, crystalline powder or free-flowing granules with a sweet taste. The drug is very slightly soluble in alcohol and has a solubility of approximately 182 mg/mL in water at 25°C. Commercially available mannitol injections have a pH of 4.5-7.
The approximate osmolarities of mannitol solutions are as follows:
Mannitol solutions should be stored at 15-30°C and protected from freezing. Solutions of mannitol are chemically stable but, in concentrations of 15% and more, mannitol may crystallize when exposed to low temperatures. If crystallization occurs, the solution should be autoclaved or warmed by immersing the container in hot water (approximately 60°C) and periodically shaking vigorously. The solution should be cooled to body temperature before administration. If all crystals cannot be completely dissolved, the solution should not be used. The addition of potassium or sodium chloride to mannitol solutions of 20% concentration or greater may cause precipitation of mannitol. Mannitol should not be added to whole blood for transfusion.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Bulk | Powder | |||
Parenteral | Injection | 5%* | ||
10%* | Mannitol Injection | |||
Osmitrol® | Baxter | |||
15%* | Mannitol Injection | |||
Osmitrol® | Baxter | |||
20%* | Mannitol Injection | |||
Osmitrol® | Baxter | |||
25%* | Mannitol Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Urogenital | Solution | 0.54% with Sorbitol 2.7%* |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
100. Goldwasser P, Fotino S. Acute renal failure following massive mannitol infusion: appropriate response of tubuloglomerular feedback? Arch Intern Med . 1984; 144:2214-6.
101. Whelan TV, Bacon ME, Madden M et al. Acute renal failure associated with mannitol intoxication: report of a case. Arch Intern Med . 1984; 144:2053-5. [PubMed 6435559]
102. Palafox NA, Jain LG, Pinano AZ et al. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA . 1988; 259:2740-2. [PubMed 3128666]