What are the pharmacodynamics of Mannitol (osmotic diuretic)?

From the Guidelines

Mannitol is an effective osmotic diuretic for reducing intracranial pressure, with a recommended dose of 0.25-1 g/kg given over 20-30 minutes, as supported by the most recent and highest quality study 1. The pharmacodynamics of mannitol involve increasing the osmolarity of plasma and renal tubular fluid, creating an osmotic gradient that pulls water from intracellular spaces into the extracellular compartment, reducing intracellular volume.

• In the kidneys, mannitol is freely filtered at the glomerulus but minimally reabsorbed in the tubules, causing increased osmotic pressure within the tubular lumen.
• This prevents water reabsorption, leading to increased urine output and reduced total body water.
• Mannitol is typically administered as a 15-25% solution, with onset of action within 15-30 minutes and duration of 4-6 hours.
• Its primary clinical applications include reducing intracranial pressure in conditions like traumatic brain injury, reducing intraocular pressure in acute glaucoma, and promoting diuresis in certain types of acute kidney injury.
• The drug is eliminated primarily through renal excretion with a half-life of about 100 minutes in patients with normal renal function.
• Caution should be used in patients with heart failure or renal impairment, as mannitol can cause fluid overload if urine output is inadequate, as noted in 1, 1, 1, 1, 1, and 1. Key considerations for mannitol administration include:
• Monitoring for hyperosmolality and adjusting the dose accordingly
• Using a filter to administer the solution and avoiding solutions that contain crystals
• Placing a urine-collecting catheter to monitor urine output
• Considering other measures to control ICP, such as hyperventilation, sedation/analgesia, head-of-bed elevation, cerebrospinal fluid drainage, barbiturates, and muscle relaxation.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

1. 1 Mechanism of Action Mannitol, when administered intravenously, exerts its osmotic diuretic effect as a solute of relatively small molecular size largely confined to the extracellular space. Mannitol hinders tubular reabsorption of water and enhances excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate By increasing the osmotic pressure of plasma and the extracellular space, intravenously administered mannitol will induce the movement of intracellular water to the extracellular and vascular spaces. This action underlies the role of mannitol in reducing intracranial pressure, intracranial edema, and intraocular pressure.

The pharmacodynamics of mannitol involve its action as an osmotic diuretic, which:

• Hinders tubular reabsorption of water
• Enhances excretion of sodium and chloride
• Increases the osmotic pressure of plasma and the extracellular space
• Induces the movement of intracellular water to the extracellular and vascular spaces This results in the reduction of intracranial pressure, intracranial edema, and intraocular pressure 2.

From the Research

Pharmacodynamics of Mannitol

• Mannitol is used to reduce intracranial pressure (ICP) and has been shown to be effective in reducing pathological ICP, proportionally to the degree of intracranial hypertension 3.
• The dose-response relationship of mannitol and ICP has been studied, and a weak linear relationship was found between change in ICP and dose 4.
• Mannitol has been shown to produce a dose-dependent increase in plasma osmolality and reduction of brain water content 5.
• The combination of mannitol and furosemide has been studied, and it was found that furosemide enhances the effect of mannitol on plasma osmolality, resulting in a greater reduction of brain water content 5.
• However, another study found that furosemide had no effect on osmolality or water content when given alone or in combination with mannitol 6.

Mechanism of Action

• Mannitol works by increasing plasma osmolality, which helps to reduce brain water content and subsequently reduce ICP 5, 6.
• The reduction in brain water content is thought to be due to the osmotic effect of mannitol, which helps to remove water from brain tissue 5.

Comparison with Other Treatments

• Glycerol has been compared to mannitol in the treatment of cerebral oedema and elevated ICP, and it was found that glycerol had comparable effectiveness to mannitol but with a lower risk of acute kidney injury and electrolyte disturbances 7.
• Glycerol may be a more tolerable alternative therapy for cerebral oedema and elevated ICP than mannitol, especially for high-risk populations of renal failure 7.