Mannitol

Drug Information: Mannitol

Mannitol is an osmotic diuretic used to reduce intracranial pressure, intraocular pressure, and to promote diuresis in acute kidney injury. It is a sugar alcohol that is poorly absorbed in the gastrointestinal tract and freely filtered at the glomerulus in the kidney. Because it is osmotically active, it draws water into the extracellular fluid and plasma, decreasing cerebral edema and intraocular pressure. It also increases renal blood flow and promotes excretion of sodium, chloride, and water by preventing their reabsorption in the renal tubules. Mannitol is typically administered intravenously due to its poor oral bioavailability.

Category

Neurological Drugs – Drugs for increased intracranial pressure

Mechanism of Action

Mannitol’s mechanism of action stems from its properties as an osmotic diuretic. After intravenous administration, mannitol is distributed throughout the extracellular fluid. Due to its relatively small molecular size and limited metabolism, mannitol is freely filtered at the glomerulus in the kidney. However, it undergoes minimal reabsorption from the renal tubules. This creates an osmotic gradient within the renal tubules, inhibiting the reabsorption of water and electrolytes (sodium and chloride) in the proximal tubule and loop of Henle. The increased osmotic pressure in the tubular fluid draws water into the tubules, increasing urine volume and promoting diuresis.

Beyond its renal effects, mannitol also impacts fluid distribution in the body. It increases the osmolality of the plasma, drawing fluid from the intracellular space into the extracellular space, including the plasma. This effect is particularly important in reducing cerebral edema, where fluid accumulates within brain tissue. By drawing water out of the brain cells and into the vascular space, mannitol decreases intracranial pressure. Similarly, it can reduce intraocular pressure by drawing fluid from the eye. It is important to note that this effect on plasma osmolality is transient, and prolonged use can lead to fluid shifts that counteract the initial benefit.

Clinical Uses

Mannitol’s clinical applications primarily revolve around its ability to increase serum osmolality and promote diuresis. Key clinical uses include:

* **Reduction of Intracranial Pressure:** Mannitol is commonly used in emergency situations to rapidly reduce intracranial pressure (ICP) associated with cerebral edema due to trauma, stroke, or tumors. By drawing fluid from the brain tissue into the vasculature, it decreases ICP and improves cerebral perfusion.
* **Reduction of Intraocular Pressure:** Mannitol is also utilized to lower intraocular pressure (IOP) in cases of acute angle-closure glaucoma or before ocular surgery. Its osmotic effect draws fluid from the vitreous humor, reducing IOP.
* **Promotion of Diuresis in Acute Kidney Injury (AKI):** Mannitol can be used to maintain urine output in the oliguric phase of AKI, particularly when caused by conditions such as rhabdomyolysis or nephrotoxic agents. It increases renal blood flow and helps prevent tubular obstruction by debris. However, its use in AKI is controversial and requires careful monitoring of fluid balance.
* **Treatment of Oliguria:** Mannitol can be used as a test dose to assess renal function and responsiveness to diuretics in oliguric patients. If urine output increases after mannitol administration, it suggests that the kidneys are capable of responding to diuretics.
* **Facilitation of Urinary Excretion of Toxic Substances:** Mannitol can be used to promote the excretion of certain toxins or drugs from the body by increasing urine flow.
* **Irrigation During Transurethral Resection of Prostate (TURP):** Mannitol solutions are sometimes used as irrigating fluids during TURP procedures to prevent TURP syndrome (hyponatremia) by limiting fluid absorption.

Dosage

Mannitol is administered intravenously (IV) and the dosage varies based on the clinical indication and patient’s condition. Here’s a general guideline:

* **Adults:**
* **Reduction of Intracranial/Intraocular Pressure:** 0.25 to 1 g/kg IV over 30-60 minutes. May be repeated every 4-6 hours as needed.
* **Promotion of Diuresis in AKI/Oliguria:** Test dose: 0.2 g/kg IV over 3-5 minutes. If no response, further doses may not be effective. Therapeutic dose: 0.5 to 1 g/kg IV.
* **Pediatrics:**
* **Reduction of Intracranial/Intraocular Pressure:** 0.25 to 1 g/kg IV over 30-60 minutes.
* **Test Dose (Oliguria):** 0.2 g/kg IV over 3-5 minutes.

* **Route of Administration:** Intravenous (IV) infusion is the only route of administration.
* **Concentration:** Available in various concentrations (e.g., 5%, 10%, 20%, 25%). Higher concentrations may require a filter during administration to prevent crystallization.

* **Important Considerations:** Dosage should be individualized based on patient’s age, weight, renal function, and clinical response. Careful monitoring of serum electrolytes, osmolality, fluid balance, and urine output is crucial during mannitol therapy.

Indications

Common indications for Mannitol use include:

* Cerebral Edema
* Increased Intracranial Pressure (ICP)
* Acute Angle-Closure Glaucoma
* Increased Intraocular Pressure (IOP)
* Oliguric phase of Acute Kidney Injury (AKI)
* Promotion of diuresis in certain poisoning cases.
* As an osmotic diuretic to promote renal blood flow
* To measure GFR (Glomerular Filtration Rate)

Contraindications

Mannitol is contraindicated in the following conditions:

* Anuria (failure of the kidneys to produce urine)
* Severe dehydration
* Active intracranial bleeding (except during craniotomy)
* Severe pulmonary edema or congestive heart failure
* Pre-existing hyperosmolality
* Hypersensitivity to mannitol
* Progressive renal disease or dysfunction after mannitol test dose

FAQ

* **Q: How does Mannitol reduce intracranial pressure?**
* A: Mannitol increases the osmolality of the blood, drawing fluid from the brain tissue into the bloodstream, thereby reducing cerebral edema and intracranial pressure.

* **Q: What are the common side effects of Mannitol?**
* A: Common side effects include electrolyte imbalances (hyponatremia, hypernatremia, hypokalemia), dehydration, headache, nausea, vomiting, and pulmonary edema. Less common, but serious side effects include acute renal failure and congestive heart failure.

* **Q: How is Mannitol administered?**
* A: Mannitol is administered intravenously (IV) by a healthcare professional. It is usually given over 30-60 minutes.

* **Q: What monitoring is required during Mannitol therapy?**
* A: Close monitoring of serum electrolytes, osmolality, fluid balance, urine output, and renal function is essential during Mannitol therapy. Neurological status should also be monitored in patients with increased intracranial pressure.

* **Q: Can Mannitol be used in patients with kidney problems?**
* A: Mannitol should be used with caution in patients with kidney problems. It is contraindicated in anuria. A test dose should be administered to assess renal responsiveness before giving higher doses.

* **Q: What should I do if I experience side effects while receiving Mannitol?**
* A: Inform your healthcare provider immediately if you experience any side effects, such as headache, nausea, vomiting, chest pain, or difficulty breathing.

* **Q: How is mannitol different from other diuretics?**
* A: Mannitol is an *osmotic* diuretic. Unlike loop diuretics or thiazide diuretics, it works by creating an osmotic gradient in the kidney tubules, drawing water into the urine. It primarily works in the proximal tubule and loop of Henle. Other diuretics work by inhibiting specific ion transporters.

* **Q: Can Mannitol be used in pregnant women?**
* A: Mannitol should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare professional.