Mannitol is a sugar alcohol (polyol) that is commonly used as a sweetener and a medication. It is naturally found in various fruits and vegetables, such as mushrooms, pumpkins, and sweet potatoes. Mannitol is about 60% as sweet as sucrose (table sugar) but has only about half the calories.

In medicine, mannitol is used as an osmotic diuretic, meaning it helps increase the amount of urine produced by the kidneys. It is often administered intravenously to help reduce intracranial pressure and intraocular pressure in conditions such as cerebral edema (brain swelling) and glaucoma. Mannitol works by drawing water into the kidneys, which increases urine production and helps reduce the pressure in the brain or eyes.

Additionally, mannitol is sometimes used as a renal function test. When given intravenously, mannitol is not metabolized by the body but is excreted unchanged in the urine, making it useful for assessing kidney function.

In the food industry, mannitol is used as a sweetener and a bulking agent in sugar-free and low-calorie foods. It is also utilized in the pharmaceutical industry as an excipient in various medications and as a component of some medical diagnostic tests.

Mannitol is a metabolically inert drug that acts as an osmotic diuretic. It is primarily used to reduce intracranial and intraocular pressures.

Mannitol Uses:

• Genitourinary irrigation solution:
  • transurethral prostatic excision irrigation or other transurethral surgical techniques
• Injection:
  • lowering of elevated intracranial pressure (related to brain mass and/or cerebral edema)
  • decreasing elevated intraocular pressure
• Off Label Use of Mannitol in Adults:
  • Enhance the effectiveness of kidney transplants

Mannitol Dose in Adults:

Mannitol dose to reduce the Intraocular pressure (IOP):

• When using mannitol to lower intraocular pressure before eye surgery, the typical dose given through an IV is between 1.5 to 2 grams per kilogram of body weight.
• It's usually administered over 30 to 60 minutes, about 1 to 1.5 hours before the surgery begins.

Mannitol Dose to reduce the Intracranial pressure (ICP) and cerebral edema(off-label dosing):

• When using mannitol to treat conditions like high intracranial pressure or brain swelling, the typical dose given through an IV is between 0.25 to 1 gram per kilogram of body weight.
• This dose can be repeated every 6 to 8 hours if necessary.
• Doctors might aim to keep the level of mannitol in the blood below 320 milliosmoles per kilogram (mOsm/kg), but it's common for this level to go higher without causing harm.
• Instead, doctors may watch out for a different marker called the serum osmol gap, aiming to keep it below 18 to 20, which helps prevent mannitol from becoming toxic.

Mannitol Dose in Kidney transplant:

For the donor:

• A dose of 12.5 grams of mannitol is typically given before nephrectomy (the surgical removal of a kidney), along with sufficient hydration.
• This dose may be repeated if necessary.

For the recipient:

• A dose of 50 grams of mannitol is typically given before kidney revascularization (the restoration of blood flow to the transplanted kidney).

Mannitol Dose to reduce the IOP (traumatic hyphema):

• When using mannitol to reduce intraocular pressure caused by traumatic hyphema (bleeding inside the eye), the typical dose given through an IV is 1.5 grams per kilogram of body weight.
• This dose is usually administered over 45 minutes and may be repeated twice daily if the intraocular pressure is above 35 mm Hg.
• In cases of extremely high pressure, the dose may be given every 8 hours.

Mannitol dose in the treatment of Transurethral irrigation:

• When mannitol is used for transurethral irrigation, a 5% urogenital solution is typically utilized.
• The solution is administered as needed for irrigation purposes.

Mannitol Dose in Children:

Note:

• Before starting intravenous (IV) mannitol therapy in patients who have severe reduction in urine output (oliguria) or are suspected of having kidney problems, it's recommended to administer a test dose first.
• This test dose helps to assess how the patient responds to mannitol and ensures their safety before proceeding with the full treatment.

Mannitol as a test dose (to assess adequate renal function):

• As a test to assess kidney function, a dose of mannitol is given intravenously.
• The typical dose is 0.2 grams per kilogram of body weight, with a maximum dose of 12.5 grams.
• It's administered over 3 to 5 minutes.
• The goal is to achieve a urine flow of at least 1 milliliter per kilogram per hour for 1 to 3 hours, indicating that the kidneys are functioning adequately.

Mannitol dose in the treatment of Acute renal failure (oliguria):

• In infants, children, and adolescents being treated for acute renal failure with low urine output (oliguria), the typical initial dose of mannitol given through an IV is between 0.5 to 1 gram per kilogram of body weight.
• This dose is infused over 2 to 6 hours.
• The usual range of doses is from 0.25 to 2 grams per kilogram of body weight.
• If necessary, the dose can be repeated every 4 to 6 hours, but it's important not to repeat the dose if the low urine output persists.
• It's worth noting that while the FDA has approved mannitol for these uses, its routine use for preventing acute renal failure or promoting urination is not typically recommended.

Mannitol Dose to reduce the Intraocular pressure (IOP):

• For reducing intraocular pressure (IOP) in infants, children, and adolescents, mannitol is typically administered intravenously at a dose of 1 to 2 grams per kilogram of body weight per dose, or alternatively, 30 to 60 grams per square meter of body surface area per dose.
• This dose is infused over 30 to 60 minutes and is usually given 1 to 1.5 hours before eye surgery.

Mannitol Dose to reduce the Intracranial pressure (ICP):

• When treating infants, children, and adolescents for reducing intracranial pressure (ICP), mannitol is typically administered intravenously within a usual range of 0.25 to 1 gram per kilogram of body weight per dose.
• This dose is infused over 20 to 30 minutes.
• If necessary, the dose can be repeated as needed to maintain a serum osmolality below 300 to 320 milliosmoles per kilogram (mOsm/kg).
• It's important to note that the manufacturer's instructions permit higher single doses of up to 2 grams per kilogram per dose.

Mannitol dose to reduce the IOP (traumatic hyphema):

• For reducing intraocular pressure (IOP) in infants, children, and adolescents with traumatic hyphema, the typical dose of mannitol administered intravenously is 1.5 grams per kilogram of body weight per dose.
• This dose is infused over 45 minutes and is given twice daily for patients with IOP greater than 35 millimeters of mercury (mm Hg).
• In cases where the pressure is extremely high, the dose may be administered every 8 hours.

Pregnancy Risk Category: C

• When mannitol is used during pregnancy, it can pass through the placenta to the baby.
• However, there isn't much information available about what happens when pregnant women have surgery and receive mannitol.
• Some studies suggest that it might decrease the amount of amniotic fluid surrounding the baby.

Mannitol use during breastfeeding:

• The presence of mannitol in breast milk is uncertain, as there's limited information available.
• Manufacturers advise considering the potential risks of exposing the infant to mannitol through breast milk against the benefits of breastfeeding and the benefits of the treatment for the mother.
• However, some other sources, like the World Health Organization (WHO), suggest that mannitol is likely compatible with breastfeeding.

Mannitol Dose in Kidney Disease:

• Mannitol should not be used in individuals with severe kidney impairment, and caution is advised in patients with existing kidney issues.
• However, it may be beneficial in reducing the risk of acute tubular necrosis when given before revascularization during kidney transplant surgery.

Mannitol Dose in Liver disease:

• No dosage adjustment is necessary.

Side effects of Mannitol:

• Cardiovascular:
  • Thrombophlebitis
  • Cardiac Failure
  • Chest Pain
  • Localized Phlebitis
  • Palpitations
  • Edema
  • Hypertension
  • Peripheral Edema
  • Tachycardia
• Dermatologic:
  • Skin Rash
  • Urticaria
  • Localized Rash
  • Pruritus
  • Diaphoresis
  • Localized Erythema
  • Skin Necrosis
• Central Nervous System:
  • Lethargy
  • Malaise
  • Confusion
  • Dizziness
  • Chills
  • Coma
  • Headache
  • Increased Intracranial Pressure (Rebound)
  • Pain
  • Seizure
• Renal:
  • Polyuria
• Endocrine & Metabolic:
  • Hyperkalemia
  • Hypernatremia
  • Dehydration
  • Fluid And Electrolyte Disturbance
  • Hypervolemia
  • Hypokalemia
  • Increased Thirst
  • Hyponatremia
  • Hypovolemia
  • Metabolic Acidosis
  • Metabolic Alkalosis
• Gastrointestinal:
  • Vomiting
  • Nausea
  • Xerostomia
• Genitourinary:
  • Urinary Retention
  • Diuresis
  • Hematuria
  • Anuria
  • Azotemia
  • Oliguria
  • Osmotic Nephrosis
• Ophthalmic:
  • Blurred Vision
• Hematologic & Oncologic:
  • Hemoconcentration
• Local:
  • Local Pain
  • Local Inflammation
  • Local Pruritus
• Neuromuscular & Skeletal:
  • Muscle Rigidity
  • Arm And/Or Wrist Pain
  • Asthenia
  • Myalgia
• Respiratory:
  • Cough
  • Pulmonary Congestion
  • Pulmonary Edema
  • Rhinitis
• Miscellaneous:
  • Fever

Contraindications to Mannitol:

• Mannitol injection should not be used in individuals who are allergic to mannitol or any ingredient in the formulation, those with anuria (a condition where the kidneys don't produce urine), severe dehydration, active bleeding inside the skull (except during surgery to open the skull), or severe pulmonary congestion or edema (fluid build-up in the lungs).
• For genitourinary irrigation, it should not be used in cases of anuria.

Warnings and precautions

Extravasation:

• Mannitol, especially at concentrations greater than 5%, can cause tissue damage if it leaks out of the vein into the surrounding tissues (extravasation).
• To prevent this, it's crucial to ensure the catheter or needle is correctly positioned before and during the intravenous (IV) infusion.
• Avoiding leakage is important because extravasation can lead to a condition called compartment syndrome, which can damage the tissues in the affected area.
• To minimize the risk, it's recommended to administer mannitol into a large central vein.

Fluid/electrolyte imbalance:

• The use of mannitol can disrupt the balance of fluids and electrolytes in the body, potentially leading to problems such as excessive fluid in the bloodstream (hypervolemia) or imbalances in electrolyte levels.
• It's important to monitor patients for signs of new or worsening heart or lung congestion, as well as for excessive urination, which can cause significant fluid and electrolyte loss.
• Close medical supervision and careful evaluation of the dose are necessary to manage these risks.
• If electrolyte disturbances occur, they should be corrected, and the dose of mannitol may need to be adjusted to prevent dehydration.

Hypersensitivity

• Serious allergic reactions, including potentially life-threatening anaphylaxis, have been reported in response to mannitol.
• If a hypersensitivity reaction occurs, it's crucial to stop the mannitol infusion immediately and provide appropriate treatment.
• Anaphylaxis requires prompt medical attention, including the administration of epinephrine and supportive care to manage symptoms and stabilize the patient.

Nephrotoxicity:

• Mannitol can potentially harm the kidneys, particularly with high doses, so caution is needed, especially in patients already taking other drugs that can damage the kidneys, those with sepsis, or those with existing kidney problems.
• To reduce the risk of kidney issues, it's important to adjust the dose to maintain serum osmolality below 320 milliosmoles per liter (mOsm/L).
• If there are signs of acute tubular necrosis (a severe kidney condition), mannitol should be stopped.
• Regular monitoring and close medical supervision can help mitigate the risk of nephrotoxicity.

Cerebral edema

• In patients undergoing treatment for cerebral edema, it's important to be cautious with mannitol use, as it can accumulate in the brain if given continuously, potentially leading to rebound increases in intracranial pressure.
• Intermittent boluses of mannitol are generally preferred to minimize this risk.
• Additionally, it's crucial to assess the patient's cardiovascular status before administering mannitol, and electrolyte-free mannitol solutions should not be mixed with blood.
• If hypotension (low blood pressure) occurs, cerebral perfusion pressure should be monitored closely to ensure adequate blood flow to the brain.

CNS effects

• Mannitol can potentially lead to central nervous system (CNS) toxicity, resulting in symptoms such as coma, confusion, or lethargy.
• This risk may be higher in patients with impaired kidney function or those taking other drugs that can affect the nervous system.
• If signs of CNS toxicity develop, mannitol should be stopped immediately.
• It's essential to monitor patients closely for any neurological symptoms while they are receiving mannitol therapy.

Renal impairment

• In individuals with renal impairment, mannitol should be used cautiously.
• If a patient has severe kidney impairment, it's important not to administer mannitol until the adequacy of renal function and urine flow is determined.
• To assess the response of the kidneys, one to two test doses of mannitol may be given before starting regular treatment.
• This cautious approach helps ensure the safety and effectiveness of mannitol therapy in patients with renal impairment.

Monitoring parameters:

• Renal Function: Assess kidney function regularly to ensure mannitol is not causing harm.
• Daily Fluid Intake and Output: Monitor the amount of fluids the patient consumes and excretes to maintain balance.
• Serum Electrolytes: Check electrolyte levels in the blood to ensure they are within normal ranges.
• Serum and Urine Osmolality: Measure the concentration of solutes in the blood and urine to evaluate kidney function.
• Infusion Site: Monitor the site where mannitol is administered for any signs of irritation or complications.

Treatment of Elevated Intracranial Pressure:

• Maintain Serum Osmolality: Some recommend keeping serum osmolality below 320 mOsm/kg to prevent acute renal tubular damage.
• Serum Osmole Gap: A better indicator of mannitol toxicity may be the serum osmole gap, with a target of less than 18 to 20 according to most clinicians.

How to administer Mannitol?

Intravenous Administration:

• Concentration and Rate: Adjust based on indication, severity, or urine flow. For cerebral edema or elevated intracranial pressure (ICP), administer over 30 to 60 minutes.
• Inspection: Check for crystals before administration. If crystals are present, warm the solution to dissolve them.
• Filter-Type Administration Set: Use for mannitol solutions ≥20% to prevent complications.
• Avoid Mixing with Blood: Crenation and agglutination of red blood cells may occur if mannitol is mixed with whole blood.

Extravasation Management:

• Stop Infusion: If extravasation happens, halt the infusion immediately and disconnect, but leave the needle/cannula in place.
• Aspirate Gently: Do not flush the line; instead, gently aspirate the extravasated solution.
• Hyaluronidase Antidote: Administer hyaluronidase to mitigate extravasation effects.
• Apply Cold Compresses: Use dry cold compresses and elevate the affected area to reduce swelling.

Hyaluronidase Administration:

• Intradermal or Subcutaneous: Inject multiple small doses around the area of extravasation.
• Proper Technique: Administer as separate injections around the periphery of the extravasation site.

Irrigation:

• Use only with appropriate transurethral urologic instruments for irrigation purposes.

Mechanism of action of Mannitol:

• Mannitol works by creating an osmotic diuresis, which means it increases the osmotic pressure in the kidneys' filtering system.
• This prevents the kidneys from reabsorbing water and electrolytes as efficiently, leading to increased urine output.
• While its exact mechanism for reducing intracranial pressure (ICP) isn't entirely clear, it's believed that mannitol reduces the thickness of the blood, temporarily improving blood flow and oxygen delivery to the brain while also narrowing small arteries in the brain's outer layer.
• This reduces the overall volume of blood in the brain and consequently lowers intracranial pressure.
• Additionally, mannitol helps draw excess water out of brain tissue, which is then eliminated through urine.

Onset of Action:

• Diuresis: Begins within 1 to 3 hours after administration.
• Reduction in Intracranial Pressure: Typically occurs within about 15 to 30 minutes.

Duration:

• Reduction in Intracranial Pressure: Lasts between 1.5 to 6 hours.

Distribution:

• Volume: Approximately 17 liters, mostly staying in the extracellular space, except in very high concentrations.
• Blood-Brain Barrier: Generally doesn't cross into the brain very much.

Metabolism:

• Mostly metabolized in the liver to glycogen.

Half-Life Elimination:

• Typically between 0.5 to 2.5 hours.
• Prolonged in renal failure, ranging from 6 to 36 hours.

Excretion:

• Primarily excreted in the urine, with around 80% of the drug leaving the body unchanged.

International Brands of Mannitol:

• Osmitrol
• Resectisol
• Ardeaosmosol MA
• Demanitol
• Demanitol AL
• Infusan M20
• Isotol
• Mannisol
• Mannits
• Neurotol-M
• Osmitrol
• Osmofundin
• Osmofundina
• Osmokab
• Osmorin
• Osmosol
• Osmosteril
• Otsumanitol
• Renitol
• Resectisol
• Rezosel

Mannitol Brand Names in Pakistan: