Reflection Coefficient and Mannitol in Raised ICP
Mannitol's reflection coefficient is near 1.0 (approximately 0.9), meaning it is largely confined to the vascular space and does not readily cross an intact blood-brain barrier, which is the fundamental property that enables its osmotic effect in reducing intracranial pressure. 1
Mechanism Related to Reflection Coefficient
The reflection coefficient (σ) represents the permeability of a membrane to a solute, ranging from 0 (freely permeable) to 1 (completely impermeable). Mannitol's high reflection coefficient across the blood-brain barrier is what makes it effective:
Mannitol remains largely confined to the extracellular space after intravenous administration, distributing within 20-40 minutes with a volume of distribution of approximately 17L in adults 1
By staying in the vascular compartment, mannitol creates an osmotic pressure gradient that draws water from brain tissue into the hypertonic intravascular environment, thereby reducing cerebral edema and intracranial pressure 2, 1
Less than 10% of mannitol undergoes tubular reabsorption, and it is freely filtered by the glomeruli, maintaining the osmotic gradient 1
Clinical Implications of the Reflection Coefficient
Effectiveness in ICP Reduction
Mannitol has been shown in controlled trials to effectively correct episodes of elevated ICP, with its use associated with improved survival in acute liver failure patients 3, 2
ICP reduction is proportional to baseline ICP values, with approximately 0.64 mmHg decrease for each 1 mmHg increment of initial ICP 4
Maximum effect occurs 10-15 minutes after administration and lasts 2-4 hours 2, 5
Dosing Based on Osmotic Properties
The recommended dose is 0.25-1 g/kg IV administered as a bolus over 15-20 minutes (approximately 250 mOsm) 3, 2, 5, 1
Smaller doses (0.25 g/kg) are as effective as larger doses in acute ICP reduction, though larger doses may provide more sustained effect at 5 hours 6
Serum osmolality must be monitored to remain below 320 mOsm/L, as exceeding this threshold indicates saturation of the osmotic gradient 3, 2, 1
Critical Caveats Related to Reflection Coefficient
Blood-Brain Barrier Disruption
When the blood-brain barrier is compromised (trauma, tumor, infection), mannitol's reflection coefficient decreases:
With repeated dosing or barrier disruption, mannitol may leak into brain tissue, potentially causing rebound intracranial hypertension 7
The cumulative amount of mannitol given over preceding hours influences ICP response more than individual dose size, implying that excessive initial dosing leads to larger subsequent doses being required 7
Timing and Frequency Considerations
Smaller, more frequent doses are as effective as larger doses while avoiding osmotic disequilibrium and severe dehydration 6
The dose may be repeated every 4-6 hours as needed, but prophylactic administration is not indicated 3, 5
Comparison with Hypertonic Saline
At equimolar doses (approximately 250 mOsm), mannitol and hypertonic saline have comparable efficacy in reducing ICP 5, 8, 9
Mannitol has superior effects on cerebral blood flow rheology through improved blood viscosity, but causes more pronounced osmotic diuresis 9
Hypertonic saline is preferred in hypotensive or hypovolemic patients, while mannitol is preferred when improved cerebral blood flow rheology is desired 5, 8
Monitoring Requirements
Cerebral perfusion pressure should be maintained above 50-60 mmHg (ideally 60-70 mmHg) while treating elevated ICP 3, 2, 8
Volume compensation is required due to osmotic diuresis, with urinary catheter placement recommended before administration 5, 8
Avoid concomitant nephrotoxic drugs or other diuretics, as mannitol increases risk of renal failure 1