What are the indications for mannitol?

Indications for Mannitol

Mannitol is primarily indicated for the reduction of intracranial pressure and brain mass, reduction of high intraocular pressure, and diagnostic measurement of glomerular filtration rate. 1

Therapeutic Indications

1. Reduction of Intracranial Pressure (ICP)

Mannitol is the principal medical strategy for treating cerebral edema and elevated intracranial pressure in various conditions:

• Ischemic Stroke with Brain Swelling

  • Used as a temporizing measure before decompressive craniectomy 2
  • Typically administered at 0.25-0.5 g/kg IV over 20 minutes, can be given every 6 hours 2
  • Maximum dose: 2 g/kg 2

• Intracerebral Hemorrhage (ICH)

  • Effective for treating acutely elevated ICP in ICH 2
  • Dose-dependent effect during ICP reduction phase 2
  • Optimal dose can be calculated based on hemorrhage location, hematoma volume, and pre-treatment ICP 2

• Traumatic Brain Injury

  • First-line osmotic agent for suspected increased ICP at 0.5-1 g/kg IV over 15-20 minutes 3
  • Duration of action: 2-4 hours 3
  • Reduces ICP from baseline values (average reduction from 22.1 mmHg to 16.8,12.8, and 9.7 mmHg at 60,120, and 180 minutes after administration) 4
  • ICP reduction is proportional to baseline values (0.64 mmHg decrease for each unit increase in initial ICP) 4

• CAR T Cell Therapy-Related Cerebral Edema

  • For management of cerebral edema with stage 3-5 papilledema or CSF opening pressure ≥20 mmHg 2
  • Initial dose: 0.5-1 g/kg; maintenance dose: 0.25-1 g/kg every 6 hours 2
  • Hold if serum osmolality ≥320 mosm/kg or osmolality gap ≥40 2

2. Reduction of High Intraocular Pressure

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

3. Diagnostic Use

• Measurement of glomerular filtration rate (GFR) 1
• Preparation: 100 mL of 20% solution (20g) diluted with 180 mL of normal saline, or 200 mL of 10% solution (20g) diluted with 80 mL of normal saline 1
• Administration: 280 mL of 7.2% solution infused at 20 mL/minute 1

Administration Considerations

Monitoring Requirements

• Serum osmolality (maintain <320 mOsm/L) 2, 3
• Electrolytes (every 4-6 hours) 2, 3
• Renal function 3
• Fluid balance 3
• Neurological status 3
• Intracranial pressure when applicable 3

Precautions During Administration

• Elevate head of bed 20-30° to facilitate venous drainage (if no spinal injury) 3
• Monitor for fluid and electrolyte imbalances 3, 1
• Compensate for osmotic diuresis with appropriate fluid management 3
• Watch for rebound ICP elevation with excessive or prolonged use 3

Contraindications

Mannitol is contraindicated in:

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

Mechanism of Action

Mannitol reduces ICP through several mechanisms:

• Creates osmotic pressure gradient across blood-brain barrier 3
• Decreases brain water content 5
• Decreases CSF formation rate (by up to 49% with high doses) 5
• Improves cerebral oxygenation 3
• Modifies cerebral hemodynamics (increases flow velocities in affected middle cerebral artery) 2

Adverse Effects

Common adverse effects include:

• Fluid and electrolyte imbalances (particularly hypernatremia and hyponatremia) 1
• Renal complications (risk increased with pre-existing renal disease) 1
• Pulmonary congestion 1
• Cardiovascular effects (hypotension, tachycardia) 1
• CNS toxicity (may increase cerebral blood flow in neurosurgical patients) 1

Clinical Pearls

• Multiple doses of mannitol do not appear to aggravate hemispheric swelling in traumatic brain edema 6
• Hypertonic saline is an effective alternative to mannitol with comparable efficacy at equiosmotic doses 3
• Avoid concomitant administration of nephrotoxic drugs or other diuretics with mannitol 1
• Discontinue mannitol if renal, cardiac, or pulmonary status worsens, or CNS toxicity develops 1