When should mannitol (mannitol) not be given to a patient with brain hemorrhage?

Contraindications and Cautions for Mannitol in Brain Hemorrhage

Mannitol should not be given to brain hemorrhage patients when serum osmolality exceeds 320 mOsm/L, when renal failure is present or developing (particularly with declining urine output), when severe hypovolemia or hypotension exists, or prophylactically in patients without clinical evidence of elevated intracranial pressure or impending herniation. 1, 2, 3

Absolute Contraindications

Renal Dysfunction

• Stop mannitol immediately if urine output declines during infusion, as this signals developing acute kidney injury 3
• Mannitol causes osmotic nephrosis that can progress to irreversible renal failure, particularly in patients with pre-existing renal disease 3
• Patients receiving nephrotoxic drugs (aminoglycosides) or other diuretics are at significantly increased risk and should not receive mannitol 3

Serum Osmolality Threshold

• Discontinue mannitol when serum osmolality exceeds 320 mOsm/L to prevent renal failure and other complications 1, 2
• The FDA label explicitly warns that accumulation of mannitol beyond this threshold causes severe adverse effects 3

Cardiovascular Instability

• Do not administer mannitol in patients with hypovolemia or hypotension, as the obligatory diuretic response will worsen hemodynamic instability 3
• Mannitol causes sudden expansion of extracellular fluid that can precipitate fulminating congestive heart failure in susceptible patients 3
• In subarachnoid hemorrhage specifically, mannitol's potent diuretic effect can compromise the euvolemia critical for preventing vasospasm 1

Clinical Situations Where Mannitol Should Be Avoided

Absence of Intracranial Hypertension

• Prophylactic administration of mannitol is not recommended in hemorrhagic stroke patients without evidence of increased ICP or signs of herniation 2
• A 2018 meta-analysis demonstrated that routine early mannitol use in supratentorial hypertensive intracerebral hemorrhage without obvious symptoms of intracranial hypertension actually increased hematoma enlargement risk, regardless of dose (250ml or 125ml) or timing (<24h, <12h, <6h) 4
• The INTERACT2 trial found no significant benefit from mannitol in acute intracerebral hemorrhage patients overall 5

Specific Hemorrhage Characteristics

• Avoid routine mannitol in small hemorrhages (<15 mL) where benefit is not demonstrated 5
• For patients with cerebral hemorrhage at acute stage, mannitol should not be used for more than 8 days due to diminishing effectiveness and accumulating risks 6

Pediatric Considerations

• Do not use mannitol in children with generalized cerebral hyperemia during the first 24-48 hours post-injury, as it may increase cerebral blood flow and worsen intracranial hypertension 3

Electrolyte and Metabolic Contraindications

Severe Hypernatremia

• Mannitol can cause hypernatremia through excessive water loss, and should be avoided when severe hypernatremia is already present 3
• The American College of Cardiology suggests choosing hypertonic saline over mannitol when hypernatremia exists 1

Hyponatremia Risk

• Mannitol shifts sodium-free intracellular fluid into the extracellular compartment, potentially lowering serum sodium and aggravating pre-existing hyponatremia 3

When to Stop Ongoing Mannitol Therapy

Treatment Failure Indicators

• Discontinue after 2-4 doses (maximum 2 g/kg total) if no clinical improvement occurs 2
• Stop if the patient shows clinical deterioration despite treatment 2
• Consider stopping if sustained neurological improvement and stable ICP are achieved 2

Duration Limits

• Mannitol's maximum effect lasts only 2-4 hours, requiring reassessment after each dose 2
• Beyond 8 days of use, mannitol should be discontinued due to saturation effects and increased risk of complications 6

Important Clinical Caveats

Rebound Intracranial Hypertension

• Prolonged use or rapid discontinuation increases risk of rebound intracranial hypertension, particularly when serum osmolality rises excessively 1

Crystallization Risk

• Do not infuse mannitol if crystals are present in the solution 3
• When infusing 25% mannitol, always use a filter in the administration set 3

Blood Product Compatibility

• Electrolyte-free mannitol should not be given with blood; if simultaneous administration is essential, add at least 20 mEq sodium chloride per liter of mannitol to avoid pseudoagglutination 3

Alternative Therapy Consideration

• When mannitol is contraindicated, hypertonic saline (3% or 23.4%) serves as an effective alternative with comparable ICP-lowering efficacy at equiosmolar doses (approximately 250 mOsm) 7, 1
• Hypertonic saline is preferable when hypovolemia or hypotension is a concern, as it has minimal diuretic effect and can increase blood pressure 1