Mannitol

Usage

• Mannitol is prescribed for the following medical conditions:
  • Reduction of elevated intracranial pressure and cerebral edema, particularly when the blood-brain barrier remains intact.
  • Reduction of elevated intraocular pressure when other methods are ineffective.
  • Promotion of diuresis in the prevention and/or treatment of the oliguric phase of acute renal failure before irreversible renal failure occurs.
  • Promotion of the elimination of renally excreted toxic substances in poisoning cases. It is used in the treatment of rhabdomyolysis and cisplatin, and methotrexate-induced acute renal failure.
  • Prevention of acute tubular necrosis or acute kidney injury in high-risk patients (e.g. patients undergoing major surgery)
  • Transurethral prostatic resection using mannitol irrigation reduces the incidence of hemolysis and hyponatremia as a consequence of absorption of hypotonic irrigation fluid during the procedure.
• Pharmacological Classification: Osmotic diuretic.
• Mechanism of Action: Mannitol exerts its effects by increasing the osmolarity of various body fluids, primarily plasma and extracellular fluid. This creates an osmotic gradient that draws water out of tissues, including the brain and eyes, and into the vascular space. In the kidneys, mannitol increases the osmotic pressure within the renal tubules, inhibiting water reabsorption and thus promoting diuresis.

Alternate Names

• International/Regional Variations: The generic name “mannitol” is generally consistent internationally.
• Brand Names: Osmitrol

How It Works

• Pharmacodynamics: Mannitol primarily works by altering osmotic gradients, leading to fluid shifts. It reduces intracranial and intraocular pressure by drawing water from these compartments into the vascular space and enhances urine output by limiting water reabsorption in the kidneys. It’s action is rapid, observed within 15 to 30 minutes.
• Pharmacokinetics:
  • Absorption: Mannitol is administered intravenously and does not undergo absorption from the gastrointestinal tract.
  • Distribution: It is primarily distributed in the extracellular fluid and does not cross the blood-brain barrier under normal circumstances.
  • Metabolism: Mannitol is not metabolized.
  • Elimination: It is excreted unchanged primarily by the kidneys through glomerular filtration. A small amount is eliminated through bile and intestinal mucosa. The duration of its effect is dose-dependent and can last from 2 to 6 hours following intravenous administration.

Dosage

Standard Dosage

Adults:

• Acute Renal Failure: 50 to 200 g/24 hours (maximum single dose of 50 g). The infusion rate is adjusted to maintain a urine flow of at least 30-50 mL/hour.
• Reduction of Intracranial Pressure: 0.25 to 2 g/kg as a 15% to 25% solution infused over 30 to 60 minutes.
• Reduction of Intraocular Pressure: 1.5 to 2 g/kg as a 15% to 25% solution infused over 30 to 60 minutes.
• Forced Diuresis (poisoning): Initial loading dose: 25g; Maintenance: Adjust dose to maintain urine output of at least 100 mL/hour and positive fluid balance of 1-2 litres.

Children:

• Renal Insufficiency Test Dose: 200 mg/kg over 3-5 minutes.
• Renal Insufficiency Treatment Dose: 0.5 to 1.5 g/kg. This may be repeated once or twice, with an interval of 4-8 hours, if necessary.
• Cerebral and Ocular Edema: 1 to 2 g/kg infused over 30 to 60 minutes.

Special Cases:

• Elderly Patients: Similar to adults, adjust dose based on weight, clinical condition, renal function, and concomitant therapy.
• Patients with Renal Impairment: Administer a test dose (200 mg/kg over 3-5 minutes) before initiating therapy to assess renal function. If there is an inadequate response to a second test dose, mannitol should be discontinued. Careful monitoring of fluid and electrolyte balance is necessary.
• Patients with Hepatic Dysfunction: No specific dosage adjustment is typically required for patients with hepatic dysfunction as mannitol is not extensively metabolised by the liver.
• Patients with Comorbid Conditions: Evaluate patient status, including fluid and electrolyte balance, renal, cardiac, and pulmonary function, and address any imbalances before and during mannitol administration. If any of these functions deteriorates during treatment, mannitol must be stopped.

Clinical Use Cases

• Intubation: Not routinely indicated.
• Surgical Procedures (to prevent acute renal failure): 50 to 100 g as a 5%, 10%, or 15% solution.
• Mechanical Ventilation: Not routinely indicated.
• Intensive Care Unit (ICU) Use: Monitor fluid and electrolyte balance, serum osmolarity, renal, cardiac, and pulmonary function closely.
• Emergency Situations (e.g., raised ICP): 0.25 to 1 g/kg IV infused over 20-30 min. Repeat doses can be given based on the osmolar gap.

Dosage Adjustments

• Monitor urine output during infusion.
• Adjust dose based on patient response and side effects.

Side Effects

Common Side Effects

• Dehydration, fluid and electrolyte imbalances (hyponatremia, hyperkalemia), headache, dizziness, nausea, vomiting, dry mouth.

Rare but Serious Side Effects

• Pulmonary edema, heart failure, seizures, acute kidney injury, allergic reactions (including anaphylaxis), thrombophlebitis, vision changes.

Long-Term Effects

• Chronic renal failure, electrolyte disturbances, fluid imbalances, urinary retention.

Adverse Drug Reactions (ADR)

• Anaphylaxis, severe hypotension, cardiac arrhythmias, metabolic acidosis, renal failure.

Contraindications

• Anuria, severe pulmonary edema or congestion, active intracranial bleeding (except during craniotomy), severe dehydration.
• Hypersensitivity to mannitol.

Drug Interactions

• May interact with digoxin, cardiac glycosides, other diuretics, lithium, and some neuromuscular blocking agents.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category C.
• Fetal Risks: Potential for fetal dehydration and electrolyte imbalances. Use with caution during pregnancy, weighing the potential benefits against the potential risks to the fetus.
• Breastfeeding: Mannitol is excreted in breast milk in small amounts. Exercise caution when administering to breastfeeding women.

Drug Profile Summary

• Mechanism of Action: Osmotic diuretic.
• Side Effects: Dehydration, electrolyte imbalances, headache, nausea, pulmonary edema, heart failure, kidney injury.
• Contraindications: Anuria, severe pulmonary edema, active intracranial bleeding (except during craniotomy), severe dehydration.
• Drug Interactions: Diuretics, digoxin, neuromuscular blocking agents, lithium.
• Pregnancy & Breastfeeding: Category C; use with caution.
• Dosage: Varies based on indication; adjust for age, weight, and renal function.
• Monitoring Parameters: Serum electrolytes, renal function, urine output, cardiac and pulmonary function, serum osmolarity.

Popular Combinations

• Mannitol is frequently combined with furosemide in the treatment of increased intracranial pressure or cerebral oedema.

Precautions

• Monitor fluid and electrolyte balance.
• Use with caution in patients with cardiac or renal disease.
• Use cautiously in patients with pre-existing electrolyte abnormalities.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Mannitol?

A: The dosage varies depending on the indication, patient age, weight, and renal function. Standard adult doses range from 0.25 to 2 g/kg intravenously.

Q2: How quickly does Mannitol lower intracranial pressure?

A: The effects of Mannitol on intracranial pressure can be observed within 15 to 30 minutes after intravenous administration.

Q3: What are the major contraindications to using Mannitol?

A: Major contraindications include anuria, severe pulmonary edema, active intracranial bleeding (except during craniotomy), and severe dehydration.

Q4: Can Mannitol be used in patients with renal impairment?

A: Use with caution and monitor closely. A test dose should be administered before initiating treatment to check if the patient can produce an adequate urine output. If the test dose fails to produce an adequate response even after a repeat test dose, mannitol is contraindicated and the patient should be re-evaluated.

Q5: What are the common side effects of Mannitol?

A: Common side effects include dehydration, fluid and electrolyte imbalances, headache, nausea, and vomiting.

Q6: How is Mannitol administered?

A: Mannitol is administered intravenously through infusion.

Q7: What are the signs of Mannitol overdose?

A: Severe dehydration, electrolyte imbalances, heart failure, pulmonary edema, seizures, and renal failure.

Q8: Can Mannitol be used in pregnant women?

A: Mannitol is a Pregnancy Category C drug, meaning that animal studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but the potential benefits may outweigh the potential risks.

Q9: How should Mannitol be stored?

A: Mannitol solutions should be stored at room temperature and protected from freezing. Check for crystals before administering.

Q10: What monitoring is necessary during Mannitol therapy?

A: Essential parameters to observe during treatment include: - Serum electrolytes: Sodium, potassium, chloride, bicarbonate. - Renal function: BUN, creatinine, urine output. - Cardiac function: Heart rate, blood pressure, signs of heart failure. - Pulmonary function: Respiratory rate, oxygen saturation, signs of pulmonary edema. - Neurological status: Level of consciousness, neurological deficits. - Serum osmolarity. - Fluid balance. - Body weight.