Introduction

An osmotic diuretic.

Uses for Mannitol

Oliguric Acute Renal Failure

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 before there is evidence of tubular necrosis or multiple vascular thrombosis.

Has been used to reduce nephrotoxicity caused by amphotericin B.

Has no effect and may be harmful if used after tubular necrosis and irreversible renal failure become established.

Reduction of Intracranial Pressure

Used prior to and during neurosurgery to reduce greatly increased intracranial pressure and for the treatment of cerebral edema. Also may be used for early treatment of cerebral edema in patients with diabetic ketoacidosis or in those in hypoglycemic coma who fail to respond to increases of blood glucose concentrations.

Reduction of Intraocular Pressure

Used to reduce elevated intraocular pressure (IOP) when the pressure cannot be lowered by other means. Especially useful for treating acute episodes of angle-closure, absolute, or secondary glaucoma and for lowering IOP prior to intraocular surgery.

Urinary Excretion of Toxins

Used alone or with other diuretics (e.g., furosemide, ethacrynic acid) to promote the urinary excretion of toxins (e.g., aspirin or other salicylates, some barbiturates, bromides, imipramine) as an adjunct to usual treatment regimens in patients with severe intoxications.

Transurethral Prostatic Resection and Transurethral Prostatectomy

Used as an irrigating solution in transurethral prostatic resection to minimize 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.

Also has been administered IV before, during, and after transurethral prostatectomy^{† [off-label]} to maintain urine output, promote rapid excretion of absorbed irrigants, and reduce the need for postoperative irrigation.

Hyperuricemia

Has been used to promote excretion of uric acid and prevent hyperuricemia and/or uric acid nephropathy^{† [off-label]} in patients who develop uricemia following chemotherapy or radiation therapy for leukemia or lymphoma.

Ciguatera Toxicity

Has been used as initial therapy, in combination with other supportive therapy, to reverse neurologic and neurosensory manifestations as well as GI manifestations of ciguatera fish poisoning^{† [off-label]}.

Edema and Ascites

Has been used alone or in conjunction with other diuretics to promote diuresis for the supportive treatment of edema and ascites^{† [off-label]} of nephrotic, cirrhotic, or cardiac origin.

Mannitol Dosage and Administration

General

• Dosage, concentration of solution, and rate of administration vary with the condition being treated and the patient’s fluid requirements, urinary output, and response to the drug.

• Do not administer drug until adequacy of patient’s renal function and urine flow have been established.

• Replace fluids, plasma, blood, and electrolytes prior to initiating therapy in patients with shock with oliguria and rising BUN.

Administration

Administer mannitol injection IV. Administer sorbitol-mannitol irrigation solution by transurethral instillation.

IV Administration

For drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using an administration set with a filter.

When used in surgical procedures to prevent oliguric acute renal failure, administration may be initiated before or immediately following surgery and may be continued postoperatively.

When used preoperatively to reduce IOP, administer 1–1.5 hours prior to surgery in order to achieve maximum reduction of pressure before surgery.

Test Dose

Administer a test dose to patients with marked oliguria or suspected inadequate renal function to establish renal response before 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, reevaluate patient, and mannitol should not be used.

Rate of Administration

Test dose in adults and children >12 years of age: Infuse over a period of 3–5 minutes to produce urine flow of ≥30–50 mL/hour.

Treatment of oliguria in adults: Infuse over 90 minutes to several hours.

Cerebral or ocular edema in children >12 years of age: Usually, infuse over 30–60 minutes.

Reduction of intracranial or IOP in adults: Usually, infuse over 30–60 minutes.

Edema and ascites^{† [off-label]} in adults and children >12 years of age: Has been infused over 2–6 hours.

Transurethral Irrigation

Sorbitol-mannitol irrigation solution is for urologic irrigation only; do not use for injection.

Administer only by transurethral instillation using appropriate and disposable urologic instrumentation.

Placing the flexible irrigation container >60 cm above the operating table may increase intravascular absorption of irrigation solution.

Dosage

Pediatric Patients

Oliguric Acute Renal Failure

Test dose

Children >12 years of age: 0.2 g/kg or 6 g/m² as a single dose.

Therapeutic purpose

Children >12 years of age: 2 g/kg or 60 g/m².

Cerebral or Ocular Edema

IV

Children >12 years of age: 2 g/kg or 60 g/m² administered as a 15 or 20% solution.

Urinary Excretion of Toxins

IV

Children >12 years of age: 2 g/kg or 60 g/m² administered as a 5 or 10% solution as needed.

Edema and Ascites†

IV

Children >12 years of age: 2 g/kg or 60 g/m² administered as a 15 or 20% solution.

Adults

Usual Dosage

IV

20–100 g administered in a 24-hour period.

Test Dose

IV

Approximately 0.2 g/kg or 12.5 g infused IV as a 15 or 20% solution (usually 100 or 75 mL of a 15 or 20% solution, respectively).

Oliguric Acute Renal Failure

Prevention

50–100 g as a 5, 10, or 15% solution. Generally, a concentrated solution is administered initially followed by a 5 or 10% solution.

Treatment of Oliguria

100 g infused IV as a 15 or 20% solution.

Management of Nephrotoxicity Associated with Amphotericin B

12.5 g administered immediately before and after each dose of amphotericin B.

Reduction of Intracranial Pressure

IV

Usually, 0.25 g/kg administered not more frequently than every 6–8 hours will achieve a maximum reduction of intracranial pressure. Alternatively, 1.5–2 g/kg infused IV as a 15, 20, or 25% solution.

A satisfactory reduction in intracranial pressure can be achieved with an osmotic gradient between blood and CSF of approximately 10 mOsmol.

Reduction of IOP

IV

Usually, 1.5–2 g/kg infused IV as a 15, 20, or 25% solution.

Some clinicians have recommended as little as 1 g or as much as 3.2 g/kg infused IV as a 15, 20, or 25% solution.

Urinary Excretion of Toxins

IV

In general, maintain a urinary output of >100 mL/hour, but preferably 500 mL/hour, and a positive fluid balance of 1–2 L.

Initially, 25 g, followed by infusion of a solution at a rate that will maintain a urinary output of ≥100 mL/hour.

In barbiturate poisoning, initially 0.5 g/kg, followed by administration of a 5 or 10% solution at a rate to maintain the desired urine output.

Alternatively, administer 1 L of a 10% solution during the first hour. Measure urine volume and pH and calculate cumulative fluid balance at the end of the first hour and subsequent 2-hour periods. If positive fluid balance is 1–2 L, administer 1 L of a 10% solution over the next 2 hours. If positive fluid balance is <1 L, replace mannitol with 1 L of 1/6 M sodium lactate over the next 2 hours (if urine pH <7) or 1 L of 0.9% sodium chloride over 2 hours (if urine pH >7). If the positive fluid balance is >2 L, administer 10% mannitol at the slowest possible rate. IV administration of furosemide recommended if the positive fluid balance >2.5 L.

Transurethral Prostatic Resection

Urogenital Irrigation

Administer a sufficient volume of sorbitol-mannitol irrigation solution; volume determined at the discretion of clinician.

Hyperuricemia†

IV

50 g/m² has been given in 24 hours.

Ciguatera Toxicity†

IV

1 g/kg.

Edema and Ascites†

IV

100 g infused IV as a 10–20% solution.

Special Populations

Geriatric Patients

Select dosage with caution, starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Contraindications

• In patients with well-established anuria caused by severe renal disease or impaired renal function who do not respond to 2 test doses. (See Test Dose under Dosage and Administration.)

• Severe pulmonary congestion or frank pulmonary edema.

• Severe CHF.

• Severe dehydration.

• Metabolic edema associated with capillary fragility or membrane permeability not associated with renal, cardiac, or hepatic disease.

• Active intracranial bleeding except during craniotomy.

• Progressive renal disease or dysfunction, including increasing oliguria and azotemia, or progressive heart failure or pulmonary congestion occurring after institution of mannitol therapy.

Warnings/Precautions

Warnings

Fluid and Electrolyte Imbalance

Risk of serious electrolyte disturbances (e.g., hyponatremia, hypernatremia, hypokalemia, hyperkalemia); may be severe enough to alter acid-base balance or depress respiration. Thiazides may be used if hypernatremia or hyperosmolality occurs.

Accumulation of mannitol caused by inadequate urinary output or rapid administration of large doses may result in overexpansion of extracellular fluid and circulatory overload causing signs and symptoms of water intoxication. Overhydration may be corrected by hemodialysis or administration of a potent diuretic (e.g., furosemide).

If urine output declines during administration, review patient’s clinical status and discontinue mannitol if necessary.

Stop or slow mannitol if central venous pressure rises or there is any other evidence of circulatory overload. Fluid administration should not exceed 1 L/day in excess of urinary output.

Sustained diuresis may result in intensification of preexisting hemoconcentration; also may result in hypovolemia which reduces glomerular filtration rate and enhances the reabsorption of sodium and water.

Prevent or treat volume and electrolyte depletion 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.

Cardiovascular Effects

Overexpansion of extracellular fluid (see Fluid and Electrolyte Imbalance under Cautions) may result in pulmonary edema and fulminating CHF, especially in patients with diminished cardiac reserve. Carefully evaluate cardiovascular status prior to administration.

Renal Effects

Possible irreversible vacuolar nephrosis.

General Precautions

Pseudoagglutination

Possible pseudoagglutination if electrolyte-free mannitol solutions are given concomitantly with blood. If blood must be given simultaneously with mannitol, add ≥20 mEq of sodium chloride to each liter of mannitol solution.

Patient Monitoring

Carefully monitor for fluid and electrolyte imbalances.

Monitor urine output; serum sodium and potassium concentrations; central venous pressure; degree of hemoconcentration or hemodilution; and renal, cardiac, and pulmonary function.

Use of Fixed-combination Urogenital Irrigation Solution

When sorbitol-mannitol irrigation solution is used, consider the cautions, precautions, and contraindications associated with sorbitol.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether mannitol is distributed into milk. Caution advised if mannitol is used.

Pediatric Use

Safety and efficacy of mannitol injections not established in children <12 years of age.

Safety and efficacy of sorbitol-mannitol irrigation solution not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age in clinical trials; however, response does not appear to differ from that in younger adults. Select dosage with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.

Substantially eliminated by kidneys; assess renal function periodically since geriatric patients more likely to have decreased renal function.

Renal Impairment

Substantially eliminated by kidneys; increased risk of toxic reactions.

Administer a test dose to patients with severe renal impairment. (See Test Dose under Dosage and Administration.)

Common Adverse Effects

Fluid and electrolyte imbalance.

General

• Dosage, concentration of solution, and rate of administration vary with the condition being treated and the patient’s fluid requirements, urinary output, and response to the drug.

• Do not administer drug until adequacy of patient’s renal function and urine flow have been established.

• Replace fluids, plasma, blood, and electrolytes prior to initiating therapy in patients with shock with oliguria and rising BUN.

Administration

Administer mannitol injection IV. Administer sorbitol-mannitol irrigation solution by transurethral instillation.

IV Administration

For drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using an administration set with a filter.

When used in surgical procedures to prevent oliguric acute renal failure, administration may be initiated before or immediately following surgery and may be continued postoperatively.

When used preoperatively to reduce IOP, administer 1–1.5 hours prior to surgery in order to achieve maximum reduction of pressure before surgery.

Test Dose

Administer a test dose to patients with marked oliguria or suspected inadequate renal function to establish renal response before 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, reevaluate patient, and mannitol should not be used.

Rate of Administration

Test dose in adults and children >12 years of age: Infuse over a period of 3–5 minutes to produce urine flow of ≥30–50 mL/hour.

Treatment of oliguria in adults: Infuse over 90 minutes to several hours.

Cerebral or ocular edema in children >12 years of age: Usually, infuse over 30–60 minutes.

Reduction of intracranial or IOP in adults: Usually, infuse over 30–60 minutes.

Edema and ascites^{† [off-label]} in adults and children >12 years of age: Has been infused over 2–6 hours.

Transurethral Irrigation

Sorbitol-mannitol irrigation solution is for urologic irrigation only; do not use for injection.

Administer only by transurethral instillation using appropriate and disposable urologic instrumentation.

Placing the flexible irrigation container >60 cm above the operating table may increase intravascular absorption of irrigation solution.

Dosage

Pediatric Patients

Oliguric Acute Renal Failure

Test dose

Children >12 years of age: 0.2 g/kg or 6 g/m² as a single dose.

Therapeutic purpose

Children >12 years of age: 2 g/kg or 60 g/m².

Cerebral or Ocular Edema

IV

Children >12 years of age: 2 g/kg or 60 g/m² administered as a 15 or 20% solution.

Urinary Excretion of Toxins

IV

Children >12 years of age: 2 g/kg or 60 g/m² administered as a 5 or 10% solution as needed.

Edema and Ascites†

IV

Children >12 years of age: 2 g/kg or 60 g/m² administered as a 15 or 20% solution.

Adults

Usual Dosage

IV

20–100 g administered in a 24-hour period.

Test Dose

IV

Approximately 0.2 g/kg or 12.5 g infused IV as a 15 or 20% solution (usually 100 or 75 mL of a 15 or 20% solution, respectively).

Oliguric Acute Renal Failure

Prevention

50–100 g as a 5, 10, or 15% solution. Generally, a concentrated solution is administered initially followed by a 5 or 10% solution.

Treatment of Oliguria

100 g infused IV as a 15 or 20% solution.

Management of Nephrotoxicity Associated with Amphotericin B

12.5 g administered immediately before and after each dose of amphotericin B.

Reduction of Intracranial Pressure

IV

Usually, 0.25 g/kg administered not more frequently than every 6–8 hours will achieve a maximum reduction of intracranial pressure. Alternatively, 1.5–2 g/kg infused IV as a 15, 20, or 25% solution.

A satisfactory reduction in intracranial pressure can be achieved with an osmotic gradient between blood and CSF of approximately 10 mOsmol.

Reduction of IOP

IV

Usually, 1.5–2 g/kg infused IV as a 15, 20, or 25% solution.

Some clinicians have recommended as little as 1 g or as much as 3.2 g/kg infused IV as a 15, 20, or 25% solution.

Urinary Excretion of Toxins

IV

In general, maintain a urinary output of >100 mL/hour, but preferably 500 mL/hour, and a positive fluid balance of 1–2 L.

Initially, 25 g, followed by infusion of a solution at a rate that will maintain a urinary output of ≥100 mL/hour.

In barbiturate poisoning, initially 0.5 g/kg, followed by administration of a 5 or 10% solution at a rate to maintain the desired urine output.

Alternatively, administer 1 L of a 10% solution during the first hour. Measure urine volume and pH and calculate cumulative fluid balance at the end of the first hour and subsequent 2-hour periods. If positive fluid balance is 1–2 L, administer 1 L of a 10% solution over the next 2 hours. If positive fluid balance is <1 L, replace mannitol with 1 L of 1/6 M sodium lactate over the next 2 hours (if urine pH <7) or 1 L of 0.9% sodium chloride over 2 hours (if urine pH >7). If the positive fluid balance is >2 L, administer 10% mannitol at the slowest possible rate. IV administration of furosemide recommended if the positive fluid balance >2.5 L.

Transurethral Prostatic Resection

Urogenital Irrigation

Administer a sufficient volume of sorbitol-mannitol irrigation solution; volume determined at the discretion of clinician.

Hyperuricemia†

IV

50 g/m² has been given in 24 hours.

Ciguatera Toxicity†

IV

1 g/kg.

Edema and Ascites†

IV

100 g infused IV as a 10–20% solution.

Special Populations

Geriatric Patients

Select dosage with caution, starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Specific Drugs