Chemistry - An osmotic diuretic, mannitol occurs as an odorless, sweet-tasting, white, crystalline powder with a melting range of 165° - 168° and a pKa of 3.4. One gram is soluble in about 5.5 ml of water (at 25°) and it is very slightly soluble in alcohol. The commercially available injectable products have approximate pH’s of 4.5 - 7.
Storage/Stability/Compatibility - Mannitol solutions are stable but are recommended to be stored at room temperature; avoid freezing.
Crystallization may occur at low temperatures in concentrations greater than 15% (see procedure for resolubolization in Dosage Forms/Preparations section). Alternatively, heated storage chambers (35° - 50°C) have been suggested to assure that soluble product is available at all times. Microwaving glass ampules/vials has been suggested, but explosions have been documented and this procedure cannot be recommended. Supersaturated solutions of mannitol in PVC bags may show a white flocullant precipitate that will tend to reoccur even after heating.
Drugs reported to be compatible with mannitol include: amikacin sulfate, bretylium tosylate, cefamandole naftate, cefoxitin sodium, cimetidine HCl, dopamine HCl, gentamicin sulfate, metoclopramide HCl, netilmicin sulfate, tobramycin sulfate, and verapamil HCl. Mannitol should not be added to whole blood products to be used for transfusion. Sodium or potassium chloride can cause mannitol to precipitate out of solution when mannitol concentrations are 20% or greater. Mannitol may be incompatible with strongly acidic or alkaline solutions.
Mannitol is reportedly stable when mixed with cisplatin for a short period of time, but advanced premixing of the drugs should be avoided because of a complex that may form between the two drugs.
Pharmacology - After intravenous administration, mannitol is freely filtered at the glomerulus and poorly reabsorbed in the tubule. The increased osmotic pressure prevents water from being reabsorbed at the tubule. To be effective, there must be sufficient renal blood flow and filtration for mannitol to reach the tubules. Although water is proportionately excreted at a higher rate, sodium, other electrolytes, uric acid and urea excretions are also enhanced.
Mannitol may have a nephro-protective effect by preventing the concentration of nephrotoxins from accumulating in the tubular fluid. Additionally, it may increase renal blood flow and glomerular filtration by causing renal arteriole dilatation, decreased vascular resistance and decreased blood viscosity.
Mannitol does not appreciably enter the eye or the CNS, but can decrease intraocular and CSF pressure through its osmotic effects. Rebound increases in CSF pressures may occur after the drug is discontinued.
Uses/Indications - Mannitol is used to promote diuresis in acute oliguric renal failure, reduce intraocular and intracerebral pressures, enhance urinary excretion of some toxins (e.g., aspirin, some barbiturates, bromides, ethylene glycol) and, in conjunction with other diuretics to rapidly reduce edema or ascites when appropriate (see Contraindications-/Precautions below). In humans, it is also used as an irrigating solution during transurethral prostatic resections.
Pharmacokinetics - Although long believed to be unabsorbed from the GI, up to 17% of an oral dose is excreted unchanged in the urine after oral dosing in humans. After intravenous dosing, mannitol is distributed to the extracellular compartment and does not penetrate the eye. Unless the patient has received very high doses, is acidotic, or there is loss of integrity of the blood-brain barrier, it does not cross into the CNS.
Only 7-10% of mannitol is metabolized, the remainder is excreted unchanged in the urine. The elimination half-life of mannitol is approximately 100 minutes in adult humans. Half-lives in cattle and sheep are reported to be between 40-60 minutes.
Contraindications/Precautions - Mannitol is contraindicated in patients with anuria secondary to renal disease, severe dehydration, intracranial bleeding (unless during craniotomy), severe pulmonary congestion or pulmonary edema.
Mannitol therapy should be stopped if progressive heart failure, pulmonary congestion, progressive renal failure or damage (including increasing oliguria and azotemia) develop after mannitol therapy is instituted.
Do not administer more than a test dose of mannitol until determining whether the patient has some renal function and urine output. Adequate fluid replacement must be administered to dehydrated animals before mannitol therapy is begun. Do not give mannitol with whole blood products, unless at least 20 mEq/l of sodium chloride is added to the solution or pseudo-agglutination may result.
Adverse Effects/Warnings - Fluid and electrolyte imbalances are the most severe adverse effects generally encountered during mannitol therapy. Adequate monitoring and support are imperative.
Other adverse effects that may be encountered include GI (nausea, vomiting), cardiovascular (pulmonary edema, CHF, tachycardia), and CNS effects (dizziness, headache, etc.).
Overdosage - Inadvertent overdosage can cause excessive excretion of sodium, potassium and chloride. If urine output is inadequate, water intoxication or pulmonary edema may occur. Treat by halting mannitol administration and monitoring and correcting electrolyte and fluid imbalances. Hemodialysis is effective in clearing mannitol.
Drug Interactions - Mannitol can increase the renal elimination of lithium.
Drug/Laboratory Interactions - Mannitol can interfere with blood inorganic phosphorus concentrations and blood ethylene glycol determinations.
a) 0.25 - 2.0 gm/kg as a 20% solution by slow IV infusion (Schultz 1986)
Monitoring Parameters -
a) Serum electrolytes, osmolality
b) BUN, serum creatinine
c) Urine output
d) Central venous pressure, if possible
e) Lung auscultation
Client Information - Mannitol should be administered by professional staff in a setting where adequate monitoring can occur.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Mannitol for Injection 180 mg/ml in 100 ml vials; Mannitol Injection® (Anthony) (Rx); Approved for use in dogs
Mannitol for Injection
5% (50 mg/ml; 275 mOsm/l) in 1000 ml
10% (100 mg/ml; 550 mOsm/l) in 500 and 1000 ml
15% (150 mg/ml; 825 mOsm/l) in 500 ml
20% (200 mg/ml; 1100 mOsm/l) in 250 and 500 ml
25% (250 mg/ml; 1375 mOsm/l) in 50 ml vials & syringes (12.5 grams/vial)
Note: Mannitol may tend to crystallize in concentrations of 15% or more when exposed to low temperatures. Resolubolization of the crystals can be accomplished by heating the bottle in hot (up to 80°C) water. Cool to body temperature before administering. An in-line IV filter is recommended when administering concentrated mannitol solutions.
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