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

Mannitol Uses:

• Injection:

  • Reduction of increased intracranial pressure (associated with cerebral edema and/or brain mass)
  • Reduction of increased intraocular pressure

• Genitourinary irrigation solution:

  • Irrigation in the transurethral prostatic resection or other transurethral surgical procedures

• Off Label Use of Mannitol in Adults:

  • Improve renal transplant function

Mannitol Dose in Adults:

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

• IV:
  • 0.25 to 1 g/kg/dose; may repeat every 6 to 8 hours as needed.
  • Some suggest maintaining serum osmolality <320 mOsm/kg.
  • However, this value is routinely exceeded without ill effect.
  • The serum osmol gap (or osmolal gap) may be the better marker for mannitol toxicity may be and the target is <18 to 20.

Mannitol dose to reduce the Intraocular pressure (IOP):

• IV:
  • 1.5 to 2 g/kg administered over 30 to 60 minutes 1 to 1.5 hours prior to surgery

Mannitol Dose to reduce the IOP (traumatic hyphema):

• IV:
  • 1.5 g/kg administered over 45 minutes twice daily for IOP >35 mm Hg
  • May administer every 8 hours in patients with extremely high pressure

Mannitol Dose in Kidney transplant:

• Donor:
  • 5 g (with adequate hydration) prior to nephrectomy; may repeat (Morris 2008)
• Recipient:
  • 50 g before kidney revascularization.

Mannitol dose in the treatment of Transurethral irrigation:

• Use a 5% urogenital solution as required for irrigation.

Mannitol Dose in Childrens:

Note:

• The manufacturer's labeling recommends a test dose prior to starting IV mannitol therapy in patients with marked oliguria or suspected renal insufficiency.

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

• Infants, Children, and Adolescents:

  • IV:
    • Initial: 0.5 to 1 g/kg/dose infused over 2 to 6 hours
    • Usual range: 0.25 to 2 g/kg/dose; may repeat dose every 4 to 6 hours
    • Do not repeat the dose if oliguria persists.

Note:

• Although FDA-labeled indications, the use of mannitol for the prevention of acute renal failure and/or promotion of diuresis is not routinely recommended.

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

• IV: 0.2 g/kg (maximum dose: 12.5 g) over 3 to 5 minutes to produce a urine flow of at least 1 mL/kg/hour for 1 to 3 hours

Mannitol Dose to reduce the Intracranial pressure (ICP):

• Infants, Children, and Adolescents:

  • IV:
    • • Usual range: 0.25 to 1 g/kg/dose infused over 20 to 30 minutes
      • Repeat as needed to maintain serum osmolality <300 to 320 mOsm/kg.

Note: The manufacturer's labeling allows for higher single doses up to 2 g/kg/dose.

Mannitol Dose to reduce the Intraocular pressure (IOP):

• Infants, Children, and Adolescents:

  • IV: 1 to 2 g/kg/dose or 30 to 60 g/m /dose infused over 30 to 60 minutes administered 1 to 1.5 hours prior to surgery

Mannitol dose to reduce the IOP (traumatic hyphema):

• Infants, Children, and Adolescents:

  • IV:
    • 1.5 g/kg/dose infused over 45 minutes twice a day for IOP >35 mm Hg
    • May administer every 8 hours in patients with extremely high pressure.

Pregnancy Risk Category: C

• Mannitol crosses over the placenta
• The information regarding the outcome of surgery in pregnancy is not available. However, it is possible that amniotic fluid volume will be reduced.

Mannitol use during breastfeeding:

• It is unknown if breast milk contains mannitol.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
• Other sources believe mannitol is compatible with breastfeeding.

Mannitol Dose in Kidney Disease:

• Contraindicated in severe renal impairment.
• Use cautiously in patients with underlying renal disease.
• May be used to reduce the incidence of acute tubular necrosis when given prior to revascularization during kidney transplantation.

Mannitol Dose in Liver disease:

• No dosage adjustment is necessary.

Side effects of Mannitol:

• Cardiovascular:

  • Cardiac Failure
  • Chest Pain
  • Edema
  • Hypertension
  • Localized Phlebitis
  • Palpitations
  • Peripheral Edema
  • Tachycardia
  • Thrombophlebitis

• Central Nervous System:

  • Chills
  • Coma
  • Confusion
  • Dizziness
  • Headache
  • Increased Intracranial Pressure (Rebound)
  • Lethargy
  • Malaise
  • Pain
  • Seizure

• Dermatologic:

  • Diaphoresis
  • Localized Erythema
  • Localized Rash
  • Pruritus
  • Skin Necrosis
  • Skin Rash
  • Urticaria

• Endocrine & Metabolic:

  • Dehydration
  • Fluid And Electrolyte Disturbance
  • Hyperkalemia
  • Hypernatremia
  • Hypervolemia
  • Hypokalemia
  • Hyponatremia
  • Hypovolemia
  • Increased Thirst
  • Metabolic Acidosis
  • Metabolic Alkalosis

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Anuria
  • Azotemia
  • Diuresis
  • Hematuria
  • Oliguria
  • Osmotic Nephrosis
  • Urinary Retention

• Hematologic & Oncologic:

  • Hemoconcentration

• Local:

  • Local Inflammation
  • Local Pain
  • Local Pruritus

• Neuromuscular & Skeletal:

  • Arm And/Or Wrist Pain
  • Asthenia
  • Muscle Rigidity
  • Myalgia

• Ophthalmic:

  • Blurred Vision

• Renal:

  • Polyuria

• Respiratory:

  • Cough
  • Pulmonary Congestion
  • Pulmonary Edema
  • Rhinitis

• Miscellaneous:

  • Fever

Contraindications to Mannitol:

• Injection:

  • Hypersensitivity to mannitol and any component of the formulation
  • Anuria
  • Severe hypovolemia
  • Active intracranial bleeding except during craniotomy
  • Pre-existing severe or persistent pulmonary congestion.

• Solution for genitourinary irrigation:

  • Anuria.

Warnings and precautions

• Extravasation:

  • It is a vesicant (at concentrations greater than 5%);
  • Before and during IV Infusion, ensure that the catheter or needle is in the correct position.
  • Avoid IV infusions that are too large, as this can cause compartment syndrome.
  • It is best to inject into a large central vein.

• Fluid/electrolyte imbalance:

  • Hypervolemia and electrolyte disorders may occur. Monitor for signs of new-onset, worsening or worsening cardiac congestion.
  • It is important to have close medical supervision and a dose evaluation as it can cause severe diuresis and fluid and electrolyte losses.
  • To avoid dehydration, correct electrolyte imbalances and adjust the dosage.

• Hypersensitivity

  • There have been reports of severe hypersensitivity reactions, including anaphylaxis, that can lead to fatalities.
  • If you experience hypersensitivity reactions, stop using Mannitol immediately and treat as such.

• Nephrotoxicity:

  • High doses may cause renal dysfunction.
  • Patients who are taking other nephrotoxic drugs, such as sepsis, or have preexisting renal disease should be cautious.
  • Adjust serum osmolality to 320 mOsm/L to minimize negative renal effects.
  • If you are experiencing acute tubular necrosis, discontinue use.

• Cerebral edema

  • Mannitol can build up in the brain in patients with cerebral edema.
  • This is due to prolonged infusions. Intermittent boluses are preferred.
  • It is important to evaluate your cardiovascular status. Do not give electrolyte-free Mannitol solutions with blood.
  • Hypotension can be detected by monitoring cerebral perfusion pressure.

• CNS effects

  • CNS toxicity (eg confusion, coma) can occur
  • Patients with impaired renal function and concomitant treatment with neurotoxic drugs may be at greater risk.
  • If CNS toxicities develop, discontinue Mannitol.

• Renal impairment

  • Be careful.
  • Patients with severe impairment should not use the medication until adequate renal function and urine flow are established.
  • To assess the renal response, you can use 1 to 2 test dosages.

Monitoring parameters:

• Renal function, daily fluid I & O, serum electrolytes, serum, and urine osmolality.
• Monitor infusion site.
• For the treatment of elevated intracranial pressure, some suggest maintaining serum osmolality <320 mOsm/kg due to the potential risk of acute renal tubular damage.
• However, this value is routinely exceeded without ill effect.
• A better marker for mannitol toxicity may be the serum osmole gap and the target used by most clinicians is <18 to 20.

How to administer Mannitol?

• IV:
  • The concentration and the rate of administration depends on indication/severity or may be adjusted to urine flow.
  • For cerebral edema or elevated ICP, administer over 30 to 60 minutes.
  • Inspect for crystals prior to administration.
  • If crystals are present, redissolve by warming solution.
  • Use filter type administration set (≤5 micron) for infusion solutions containing mannitol ≥20%.
  • Do not administer with blood.
  • Crenation and agglutination of red blood cells may occur if administered with whole blood.

• Vesicant (at concentrations >5%);

  • Ensure proper catheter or needle position prior to and during IV infusion.
  • Avoid extravasation of IV infusions.
  • Administration into a large central vein is recommended.

• Extravasation management:

  • If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place).
  • Gently aspirate extravasated solution (do NOT flush the line).
  • Initiate hyaluronidase antidote.
  • Remove needle/cannula
  • Apply dry cold compresses.
  • Elevate extremity.

• Hyaluronidase:

  • Intradermal or SubQ:
    • Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections (using a tuberculin syringe) into the area of extravasation at the leading edge in a clockwise manner
    • SubQ: Administer multiple 0.5 to 1 mL injections of a 15 units/mL solution around the periphery of the extravasation.

• Irrigation:

  • Administer using only the appropriate transurethral urologic instrumentation.

Mechanism of action of Mannitol:

• Produces an osmotic urisis by raising the osmotic Pressure of Grünular Filterate.
• This inhibits tubular water reabsorption and electrolytes, and increases urinary output.
• It is not clear how intracranial pressure (ICP), works.
• Mannitol, however, is believed to reduce ICP by reducing blood viscosity.
• This transiently increases cerebral bloodflow and oxygen transport and constricts the pial arterioles.
• This reduces cerebral blood volume and ICP.
• Mannitol also reduces ICP because it withdraws water from the brain parenchyma, and excretes it in the urine.

The onset of action:

• Diuresis: 1 to 3 hours;
• Reduction in intracranial pressure: ~15 to 30 minutes

Duration:

• Reduction in intracranial pressure: 1.5 to 6 hours

Distribution:

• Remains confined to extracellular space (except in extreme concentrations)
• Does not penetrate the blood-brain barrier (generally, penetration is low)

Metabolism:

• Minimally hepatic to glycogen

Half-life elimination:

• 0.5 to 2.5 hours
• 6 to 36 hours in renal failure

Excretion:

• Urine (~80% as unchanged drug)

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: