Mannitol in Hemorrhagic Stroke
Mannitol should be reserved as a temporizing measure for hemorrhagic stroke patients with clinical evidence of elevated intracranial pressure (ICP) or impending herniation, but it is not routinely recommended and has not been proven to improve mortality or functional outcomes.
Indications for Use
Use mannitol only when there is clinical evidence of increased ICP or herniation, not prophylactically 1, 2. The American Heart Association guidelines specifically recommend osmotherapy for patients whose condition is deteriorating secondary to increased intracranial pressure, including those with herniation syndromes 1.
Key clinical indicators include:
- ICP measurements >25 mm Hg (if monitoring available) 3
- Pupillary abnormalities suggesting herniation 3
- Clinical deterioration with signs of brain stem compression 1
Dosing Protocol
Administer 0.25 to 0.5 g/kg IV over 20 minutes, repeated every 6 hours as needed 1, 4. The maximum total daily dose is 2 g/kg 1, 4.
- Onset of action: 10-15 minutes 2, 4
- Peak effect: 10-15 minutes after administration 4
- Duration: 2-4 hours 2, 4
Critical Monitoring Parameters
Discontinue mannitol when serum osmolality exceeds 320 mOsm/L 2, 4. Additional stopping criteria include:
- After 2-4 doses without clinical improvement 2
- Clinical deterioration despite treatment 2
- Development of renal failure or significant volume depletion 1
Monitor fluid balance, serum sodium, chloride, and osmolality throughout treatment 4. Place a urinary catheter before administration due to osmotic diuresis 4.
Evidence Limitations and Outcomes
Despite widespread use, mannitol has not been proven to improve functional outcomes or reduce mortality in hemorrhagic stroke 2, 5. A Cochrane systematic review found no evidence that routine use of mannitol reduced cerebral edema or improved stroke outcomes 2, 5.
The INTERACT2 trial analysis (2839 patients with intracerebral hemorrhage) showed:
- No significant difference in death or major disability between mannitol and non-mannitol groups (OR 0.87,95% CI 0.71-1.07) 6
- Possible benefit in larger hematomas (≥15 mL), though not consistent across all analyses 6
- No excess serious adverse events 6
Even with intensive medical management including mannitol, mortality in patients with increased ICP remains 50-70% 1, 5.
Mechanism and Physiological Effects
Mannitol reduces ICP through osmotic effects, drawing intracellular water into the extracellular and vascular spaces 7. Research demonstrates:
- ICP reduction is proportional to baseline ICP values (0.64 mm Hg decrease per 1 mm Hg baseline elevation) 8
- Average ICP decreases from 22.1 mm Hg to 16.8 mm Hg at 60 minutes, 12.8 mm Hg at 120 minutes, and 9.7 mm Hg at 180 minutes 8
- Improves cerebral blood flow in both hemispheres 9
Alternative Considerations
Hypertonic saline (3% or 23.4%) is an effective alternative with comparable efficacy at equiosmotic doses and may have longer duration of action 2, 4, 10. Hypertonic saline may be preferred when:
- Hypovolemia or hypotension is present 4
- Hypernatremia exists (favoring mannitol instead) 4
- Multiple doses are needed (less risk of rebound ICP) 1
Studies comparing hypertonic saline to mannitol show HS-HES may lower ICP more effectively (maximum decrease 11.4 mm Hg vs 6.4 mm Hg) 3, though mannitol increases cerebral perfusion pressure more 3.
Definitive Management
Surgical decompression (hemicraniectomy) should be considered as definitive treatment when medical management fails 2, 5. Mannitol serves only as a temporizing bridge to surgery in patients with massive cerebral edema 1, 2.
For large hemispheric hemorrhages where herniation is the primary concern, surgical intervention may be more appropriate than continued osmotic therapy 2.
Adjunctive Measures
Maintain non-pharmacological ICP management throughout treatment 2, 4:
- Elevate head of bed 20-30 degrees 1
- Keep head midline, avoid neck rotation 1
- Correct hypoxemia, hypercarbia, and hyperthermia 1
- Avoid hypoosmolar fluids (5% dextrose) 1
- Consider CSF drainage if hydrocephalus present 1
Important Caveats
- Do not use prophylactically in hemorrhagic stroke without evidence of increased ICP 2
- Mannitol can cause osmotic diuresis, volume depletion, renal failure, and rebound intracranial hypertension 1
- Avoid in patients with renal impairment (elimination half-life prolonged to 36 hours) 7
- Do not use solutions containing crystals; administer through a filter 4
- Antihypertensive agents that cause cerebral vasodilation should be avoided during treatment 1