What is mannitol, its indications, and contraindications for use in patients with increased intracranial pressure?

What is Mannitol, Its Uses, and Contraindications

Definition and Mechanism

Mannitol is an osmotic diuretic that works by creating an osmotic gradient across the blood-brain barrier, extracting fluid from edematous cerebral tissue into the intravascular space, thereby reducing intracranial pressure and brain mass. 1

The drug requires an intact blood-brain barrier to be maximally effective, making it particularly useful for vasogenic edema (such as intracerebral hemorrhage with mass effect) and acute hydrocephalus with elevated ICP. 1

Primary Indications

Mannitol is FDA-approved for: 2

• Reduction of intracranial pressure and brain mass
• Reduction of high intraocular pressure
• Measurement of glomerular filtration rate (diagnostic use)

Specific Clinical Scenarios for ICP Management

Mannitol should be administered when there are specific clinical signs of elevated ICP or impending brain herniation, not routinely based on imaging alone: 1, 3

• Declining level of consciousness
• Pupillary abnormalities (anisocoria or bilateral mydriasis)
• Decerebrate posturing
• Glasgow Coma Scale ≤8 with significant mass effect
• Acute neurological deterioration suggesting herniation
• ICP monitoring showing sustained ICP >20 mm Hg (if monitoring in place)

Dosing Protocol

The American Heart Association recommends 0.25 to 0.5 g/kg IV administered over 20 minutes, repeated every 6 hours as needed, with a maximum daily dose of 2 g/kg. 1, 3

Key dosing considerations: 1, 3

• Smaller doses (0.25 g/kg) are as effective as larger doses (0.5-1 g/kg) for acute ICP reduction, with ICP decreasing from approximately 41 mm Hg to 16 mm Hg regardless of dose
• The standard dose is approximately 250 mOsm infused over 15-20 minutes 4
• Onset of action occurs within 10-15 minutes, with peak effect shortly after administration and effects lasting 2-4 hours 1
• A urinary catheter must be placed before administration due to osmotic diuresis 1, 5

Absolute Contraindications

Mannitol is contraindicated in the following conditions per FDA labeling: 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 institution of mannitol therapy
• Known hypersensitivity to mannitol

Special Clinical Context: Moyamoya Disease

In perioperative moyamoya disease, mannitol should be avoided entirely as it can precipitate cerebral ischemia in this population with compromised cerebrovascular reserve. 4

Critical Monitoring Requirements

Serum Osmolality

Discontinue mannitol when serum osmolality exceeds 320 mOsm/L to prevent renal failure and other complications. 1, 3, 5, 6

• Monitor serum osmolality every 6 hours during active therapy 1
• Serum osmolality increases of ≥10 mOsm are associated with effective ICP reduction 1
• Mannitol may precipitate acute renal failure if serum osmolarity exceeds 320 mOsm/L 6

Electrolytes and Metabolic Parameters

Monitor every 6 hours during active mannitol therapy: 1

• Sodium and potassium
• Complete metabolic profile
• Fluid status and urine output

Hemodynamic Monitoring

Maintain cerebral perfusion pressure (CPP) at 60-70 mm Hg during mannitol administration. 1, 4

• Patients with low CPP (<70 mm Hg) have autoregulatory vasodilation that allows mannitol's vasoconstrictive mechanism to work effectively 1, 7
• Monitor blood pressure closely, particularly in elderly patients with cardiovascular disease 1

Important Clinical Caveats

Hypotension and Hypovolemia

In patients with hypotension or hypovolemia, hypertonic saline is superior to mannitol. 4

• Mannitol is a potent diuretic that can cause hypovolemia and hypotension 1
• If mannitol must be used in borderline hypotension, initiate aggressive fluid resuscitation with crystalloids before or concurrent with administration 4
• With systolic BP 90/60 (MAP ~70 mm Hg), if ICP is elevated, CPP may already be critically low 4

Rebound Intracranial Hypertension

Mannitol can cause rebound intracranial hypertension, particularly with prolonged use or rapid discontinuation. 1

• Risk increases when serum osmolality rises excessively 1
• Excessive cumulative dosing allows mannitol to cross into brain parenchyma, reversing the osmotic gradient 1
• Use a gradual dose reduction strategy (extending dosing intervals progressively) to prevent rebound 1
• However, if acute renal failure develops, this is an absolute contraindication requiring immediate discontinuation rather than taper 1

Fluid Management

Avoid hypoosmotic fluids and use isoosmotic or hyperosmotic maintenance fluids when administering mannitol. 1, 3

• Replace urine output volume for volume with appropriate crystalloid solutions 5
• Mannitol induces osmotic diuresis requiring volume compensation 4

Mannitol vs. Hypertonic Saline

At equiosmolar doses (approximately 250 mOsm), mannitol and hypertonic saline have comparable efficacy for reducing ICP. 1, 3, 4

When to Choose Mannitol:

• Hypernatremia is present 1
• Improved cerebral blood flow rheology is desired 1
• Among therapies that decrease ICP, only mannitol has been associated with improved cerebral oxygenation 4

When to Choose Hypertonic Saline:

• Hypovolemia or hypotension is a concern 1, 4
• Hypertonic saline has minimal diuretic effect and increases blood pressure 1

Limitations as Temporizing Measure

Mannitol is only a temporizing measure and does not improve long-term outcomes in ischemic brain swelling, with mortality remaining 50-70% despite intensive medical management. 3

• Decompressive craniectomy performed within 48 hours is the most definitive treatment for large hemispheric infarcts with mass effect 3
• Mannitol should be used in conjunction with other ICP control measures: head elevation, sedation and analgesia, CSF drainage, hyperventilation (cautiously), and neuromuscular blockade as needed 1