Mannitol is a sugar alcohol administered intravenously, primarily used in clinical settings to reduce elevated intracranial pressure or brain swelling. The goal of this treatment is to prevent serious complications by lowering the pressure inside the skull, often following a traumatic brain injury or stroke. Hypernatremia is a condition defined by an abnormally high concentration of sodium in the blood. The relationship between mannitol and hypernatremia is complex, depending heavily on the timing of measurement and the patient’s overall hydration status.
Mannitol’s Role as an Osmotic Diuretic
Mannitol functions as an osmotic diuretic, promoting the movement of water across semipermeable membranes based on concentration differences. When introduced into the bloodstream, it is freely filtered by the kidneys’ glomeruli but is poorly reabsorbed from the renal tubules. This non-reabsorbed solute increases the fluid’s osmolality, or solute concentration, within the kidney tubules.
The increased osmolality creates an osmotic gradient that strongly inhibits the reabsorption of water back into the bloodstream. Water follows the mannitol molecules into the urine, leading to a significant increase in urine volume, a process known as osmotic diuresis. This same osmotic principle draws free water from the extravascular space, such as edematous brain tissue, into the intravascular space. This fluid shift reduces swelling and pressure within the skull, achieving the drug’s primary therapeutic goal.
The Immediate Effect: Transient Hyponatremia
The initial administration of mannitol triggers a rapid fluid shift that temporarily alters the patient’s sodium balance. As the drug enters the circulation, it elevates the plasma osmolality, moving water out of the body’s cells and into the blood vessels. This influx of water rapidly expands the volume of fluid in the bloodstream.
This sudden increase in blood volume effectively dilutes the existing concentration of sodium in the serum. The result is an immediate, but usually brief, drop in the measured serum sodium level, termed dilutional hyponatremia. This effect is a consequence of volume expansion rather than an actual sodium loss. Because the underlying cause is the presence of osmotically active mannitol, this is classified as hypertonic hyponatremia.
Delayed Risk: Developing Hypernatremia
Mannitol’s effect on serum sodium concentration shifts dramatically as the body begins to excrete the drug. As the kidneys filter out the mannitol, the resulting osmotic diuresis leads to a massive loss of water. This process results in the excretion of a volume of water that is disproportionately high compared to the amount of sodium excreted.
The patient loses a large volume of electrolyte-free water. If this significant water loss is not adequately replaced, the remaining sodium in the body becomes concentrated, leading to true hypernatremia. This delayed consequence of the diuretic phase may occur in 10% to 21% of patients receiving mannitol over several days. This secondary hypernatremia is a sign of net free water deficit.
Clinical Monitoring and Patient Management
Because of the two-phased effect on sodium, close clinical monitoring is necessary during mannitol administration to prevent dangerous electrolyte imbalances. Healthcare professionals must frequently measure serum sodium and serum osmolality, often every four to six hours in high-risk patients or those receiving repeated doses. Monitoring serum osmolality is particularly helpful because levels above 320 mOsm/kg are associated with an increased risk of acute kidney injury and are a common threshold for withholding further doses.
Individualized fluid replacement strategies are a management cornerstone to mitigate the risks of both hyponatremia and delayed hypernatremia. To prevent free water deficit, clinicians often replace fluid losses from diuresis with hypotonic fluids, such as half-normal saline or 5% dextrose in water (D5W). If hypernatremia develops, management involves carefully correcting the free water deficit by administering hypotonic fluids slowly. This cautious approach prevents overly rapid correction, which could lead to complications like cerebral edema.