Manitol

Uses

Manitol is principally used by IV infusion as an osmotic diuretic to preserve renal function in acute renal failure and to reduce raised intracranial and intraocular pressure. Manitol is also used as an irrigating solution to prevent hemolysis and hemoglobin buildup during transurethral prostatic resection. It is useful in the management of acute drug poisoning where a route of elimination is through kidney. Besides these, it is also used in symptomatic relief of edema, reperfusion injury, termination of pregnancy, and bowel preparation. So, Manitol is used for-

Renal insufficiency, Reperfusion injury, Raised intracranial pressure, Bladder irrigation, Raised intraocular presure, Bowel preparation, Edematous status, As a prophylactic in renal failure, Management of poisoning, Termination of Pregnancy

Manitol is also used to associated treatment for these conditions: Acute Renal Failure (ARF), Cystic Fibrosis (CF), Edema of the cerebrum, Increased Intra Ocular Pressure (IOP), Bladder irrigation therapy

How Manitol works

Manitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Manitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Manitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR).

The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance.

Dosage

Manitol dosage

The adult dose of Manitol ranges from 50 to 100 gm by IV infusion. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 ml/hr. Total dosage, concentration and the rate of administration depends on fluid requirement, urinary output and the severity of the condition being treated

Renal insufficiency-

• Adults: 50 to 100 g of Manitol administered at a rate adjusted to maintain a urine flow of at least 30 to 50 ml/hr.
• Children: 2 gm/kg or 60 gm/m2of body surface area administered over a period of 2 to 6 hrs.

Cerebral edema, elevated intracranial pressure, elevated intraocular pressure, Glaucoma-

• Adults: 1.5 to 2 gm/kgadministered over a period of 30 to 60 minutes.
• Children: 1 to 2 gm/kg body wt. or 30 to 60 gm/m2 of body surface area administered over a period of 30 to 60 mins.

Adjunctive therapy for removal of toxic substances-

• Adults: 50 to 200 g of Manitol administered at a rate adjust to maintain a urine flow of at least 100 to 500 ml/hr.
• Children: 2 gm/kg or 60 gm/m2of body surface area

For termination of pregnancy 50 gm of Manitol (250 ml of Manitol) is instilled into the amniotic cavity which induces abortion in a high proportion of pregnancies.

Side Effects

The most common side effects associated with Manitol intravenous infusion is fluid and electrolytes imbalance including circulatory overload and acidosis at high doses. Other side effects include nausea, vomiting, thirst, headache, dizziness, fever, tachycardia, chest pain, hyponatraemia, dehydration, blurred vision, urticaria, and hypertension or hypotension.

Toxicity

Manitol overdose may result in bronchoconstriction and should be counteracted using a short-acting bronchodilator and other symptomatic and supportive care, as necessary.

Precaution

Careful monitoring of rate of administration of Manitol is necessary to avoid fluid and electrolyte imbalance and circulatory overloading. The infusion should be discontinued if the patient develops signs of progressive renal dysfunction, heart failure or pulmonary congestion. Manitol should not be administered with whole blood.

Interaction

Increased nephrotoxicity with ciclosporin.

Food Interaction

Manitol Drug Interaction

Unknown: lorazepam, celecoxib, sulfamethoxazole / trimethoprim, dexamethasone, glucose, phenytoin, levetiracetam, insulin glargine, furosemide, sodium chloride, acetaminophen, lvp solution with potassium, acetaminophen, multivitamin, thiamine, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol, phytonadione

Manitol Disease Interaction

Major: fluid overloadModerate: hyperosmolar effects

Volume of Distribution

Manitol administered intravenously has a volume of distribution of 34.3 L.

Elimination Route

Approximately 7% of ingested mannitol is absorbed during gastrointestinal perfusion in uremic patients.

Inhalation of 635 mg of mannitol powder yields a plasma C_max of 13.71 μg/mL in 1.5 hours (T_max) and a mean systemic AUC of 73.15 μg*h/mL.

Half Life

Manitol has an elimination half-life of 4.7 hours following oral administration; the mean terminal elimination half-life is similar regardless of administration route (oral, inhalation, and intravenous.

Clearance

Intravenous administration of mannitol yields a total clearance of 5.1 L/hr and renal clearance of 4.4 L/hr.

Elimination Route

Manitol is primarily excreted unchanged in the urine. Following oral inhalation of 635 mg of mannitol in healthy volunteers, 55% of the total dose was recovered unchanged in the urine; following oral or intravenous administration of 500 mg, the corresponding values were 54 and 87%, respectively.

Pregnancy & Breastfeeding use

Safety of Manitol intravenous infusion in pregnancy has not been established yet. No information is available on the excretion of mannitol in breast milk and should be administered after careful consideration of risk-benefit ratio.

Contraindication

Manitol intravenous infusion is contraindicated in patients with pulmonary edema or congestive heart failure. It is also contraindicated during inadequate urine flow, dehydration or acidosis, intracranial bleeding and in patients with renal failure unless a test dose has produced a diuretic response

Storage Condition

Manitol should be stored at a temperature of 20° to 30°. Exposure to lower temperatures may cause deposition of crystals, which should be dissolved by warming the bottle in hot water for about 30 minutes. Cool to body temperature before using. If all crystals can not be dissolved, the solution should not be used. The content of open containers should be used promptly. Unused contents should be discarded.

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