What is the recommended use and dosage of Mannitol (mannitol) in medical treatment?

Recommended Use and Dosage of Mannitol in Medical Treatment

Mannitol is recommended at a dose of 0.25 to 2 g/kg body weight as a 15% to 25% solution administered over 30-60 minutes for the reduction of intracranial pressure (ICP) and brain mass. 1

Primary Indications

• Mannitol is indicated for the reduction of intracranial pressure and brain mass in patients with traumatic brain injury, cerebral edema, or signs of brain herniation 1
• It is also used for reduction of high intraocular pressure 1
• Mannitol can be used diagnostically for measurement of glomerular filtration rate 1

Dosing Guidelines for Intracranial Hypertension

Adult Dosing

• Standard dose: 0.25 to 2 g/kg body weight as a 15% to 25% solution administered over 30-60 minutes 1
• For small or debilitated patients: 500 mg/kg 1
• The American Heart Association recommends mannitol at 0.25 to 0.5 g/kg IV administered over 20 minutes, which can be given every 6 hours 2
• Maximum daily dose should not exceed 2 g/kg to avoid potential adverse effects 2

Pediatric Dosing

• 1 to 2 g/kg body weight or 30 to 60 g/m² body surface area over a period of 30 to 60 minutes 1

Traumatic Brain Injury Specific Dosing

• For threatened intracranial hypertension or signs of brain herniation: 20% mannitol at a dose of 250 mOsm, infused over 15-20 minutes 3
• Lower starting dose of 0.25 g/kg is recommended for patients with subdural hematoma and hyponatremia 4

Pharmacodynamics and Clinical Effects

• Onset of action: 10-15 minutes after administration 2
• Duration of effect: 2-4 hours 2
• Mechanism: Creates an osmotic gradient that reduces cerebral edema by drawing water from brain tissue into the intravascular space 4
• Mannitol is the only osmotic agent shown to improve cerebral oxygenation among ICP-lowering therapies (compared to external ventricular drainage and hyperventilation) 3

Monitoring and Precautions

• Serum osmolality should be monitored to ensure it remains below 320 mOsm/L 2, 4
• Continuous neurological assessment is required during treatment 4
• Monitor fluid, sodium, and chloride balances due to mannitol's osmotic diuresis effect 3
• Volume compensation may be necessary due to the diuretic effect 3

Contraindications

• Well-established anuria due to severe renal disease 1
• Severe pulmonary congestion or frank pulmonary edema 1
• Active intracranial bleeding except during craniotomy 1
• Severe dehydration 1
• Progressive heart failure or pulmonary congestion after institution of mannitol therapy 1
• Known hypersensitivity to mannitol 1

Important Clinical Considerations

• The effect of mannitol on ICP is dose-dependent during the period of ICP reduction 4, 5
• Smaller, more frequent doses may be as effective in reducing ICP while avoiding risks of osmotic disequilibrium and severe dehydration 6
• Studies suggest that doses of 1.0 g/kg or higher consistently reduce ICP by at least 10%, while lower doses may not always be effective 7
• Excessive administration of mannitol may lead to larger doses being required to control ICP in subsequent treatments 8
• Response to mannitol is influenced by hemorrhage location and hematoma volume in patients with intracerebral hemorrhage 5
• Mannitol is often used as a temporizing measure before patients undergo definitive treatment such as decompressive craniectomy 2

Adverse Effects and Risks

• Renal complications including renal failure, especially with pre-existing renal disease or concomitant use of nephrotoxic drugs 1
• Fluid and electrolyte imbalances including hypernatremia and hyponatremia 1
• Central nervous system toxicity, including increased cerebral blood flow and risk of postoperative bleeding in neurosurgical patients 1
• Other common adverse reactions include pulmonary congestion, acidosis, electrolyte loss, dryness of mouth, thirst, marked diuresis, urinary retention, headache, blurred vision, convulsions, nausea, vomiting, and hypotension 1

Despite intensive medical management with mannitol, mortality in patients with increased ICP remains high (50-70%) 2, highlighting the importance of using this medication as part of a comprehensive approach to managing intracranial hypertension.