What are the indications and dosing of mannitol (Intravenous (IV) medication) in managing Intracerebral Hemorrhage (ICH)?

Indications and Dosing of Mannitol in Intracerebral Hemorrhage (ICH)

Mannitol should be used in ICH patients with clinical evidence of elevated intracranial pressure (ICP), not as a routine treatment for all ICH patients. 1

Indications for Mannitol in ICH

• Mannitol is indicated for the reduction of intracranial pressure and brain mass in patients with ICH 2

• Clinical signs of elevated ICP requiring mannitol treatment include:

  • Neurological deterioration not attributable to systemic causes 3
  • Pupillary abnormalities (anisocoria or mydriasis) 3
  • Decerebrate posturing or other signs of herniation 3
  • Directly measured elevated ICP (>20-25 mmHg) in monitored patients 3, 1

• Mannitol is not recommended for routine or prophylactic use in all ICH patients without evidence of increased ICP 1, 4

Dosing Recommendations

• FDA-approved dosing for reduction of intracranial pressure 2:

  • Adults: 0.25 to 2 g/kg body weight as a 15% to 25% solution administered over 30-60 minutes
  • Small or debilitated patients: 500 mg/kg
  • Pediatric patients: 1 to 2 g/kg body weight or 30 to 60 g/m² body surface area over 30-60 minutes

• Typical clinical administration 1:

  • 0.25 to 0.5 g/kg IV administered over 20 minutes
  • Can be given every 6 hours as needed
  • Maximum dose: 2 g/kg 1

• Dosing considerations 5:

  • The effect of mannitol on ICP is dose-dependent during the period of ICP reduction
  • Optimal mannitol dose can be calculated based on:
    • Hemorrhage location (supratentorial vs. infratentorial)
    • Hematoma volume
    • Pre-treatment ICP measurement

Mechanism and Effects

• Mannitol creates an osmotic gradient across the blood-brain barrier, causing water displacement from brain tissue to the intravascular space 3
• Maximum effect occurs after 10-15 minutes and lasts for 2-4 hours 3, 6
• A single bolus of mannitol modifies cerebral hemodynamics by increasing flow velocities in the affected middle cerebral artery in ICH patients 1, 6
• Mannitol may have a shorter duration of action compared to hypertonic saline in treating ICP in ICH 7

Monitoring and Precautions

• Serum osmolality should be monitored and maintained below 320 mOsm/L 3, 2
• Avoid concomitant administration of nephrotoxic drugs or other diuretics with mannitol 2
• Discontinue mannitol if renal, cardiac, or pulmonary status worsens 2
• Mannitol is contraindicated in 2:
  • Well-established anuria due to severe renal disease
  • Severe pulmonary congestion or frank pulmonary edema
  • Active intracranial bleeding except during craniotomy
  • Severe dehydration
  • Progressive heart failure or pulmonary congestion after mannitol therapy initiation

Evidence on Efficacy

• The 2022 AHA/ASA guidelines note that hyperosmolar therapy (including mannitol) is the principal medical strategy for treating cerebral edema, but the duration of effects in ICH is unclear 1
• A 2011 meta-analysis suggested that hypertonic saline may be more effective than mannitol for treating elevated ICP 1
• A 2018 meta-analysis found that routine mannitol use in early supratentorial hypertensive ICH could lead to hematoma enlargement 4
• The INTERACT2 trial analysis found that mannitol seems safe but might not improve outcomes in patients with acute ICH, though there was a suggestion of benefit in patients with larger hematomas (≥15 mL) 8
• The European Stroke Organisation guidelines note insufficient evidence from RCTs to make strong recommendations on measures to lower ICP for adults with acute ICH 1

Alternative Treatments

• Hypertonic saline (3% or 23.4%) is an alternative to mannitol and may have a longer duration of action in some cases 3, 7
• Surgical interventions such as decompressive craniectomy may be necessary for refractory intracranial hypertension 9