What is an example of hyperosmolar therapy? A look at mannitol and hypertonic saline

October 11, 2025 •

4 min read

Hyperosmolar therapy has been used since the early 20th century to manage cerebral edema. What is an example of hyperosmolar therapy? Common examples include the intravenous administration of mannitol or hypertonic saline, which create an osmotic gradient to shift fluid and reduce pressure in the brain.

Quick Summary

Mannitol and hypertonic saline are primary examples of hyperosmolar therapy used in critical care to decrease intracranial pressure and treat cerebral edema. These agents draw fluid from brain tissue by increasing the osmolality of the blood, mitigating secondary brain injury following conditions like TBI or stroke. Each agent has a distinct mechanism and side-effect profile.

Key Points

Hypertonic Saline (HTS): A common example of hyperosmolar therapy, HTS is used to reduce intracranial pressure by drawing fluid from swollen brain tissue into the bloodstream.
Mannitol's Role: Mannitol, a sugar alcohol, is another primary example that acts as an osmotic diuretic, pulling fluid out of the brain to decrease intracranial pressure.
Mechanism of Action: Both HTS and mannitol create an osmotic gradient across the blood-brain barrier, causing water to shift from the brain parenchyma into the vascular space, thereby reducing cerebral edema.
Clinical Applications: Hyperosmolar therapy is indicated for acute neurological emergencies like traumatic brain injury, stroke, and hemorrhage, where elevated intracranial pressure is a critical concern.
Key Differences: HTS is often preferred in hypotensive patients as it helps maintain blood pressure, while mannitol's diuretic effect can lead to hypotension and requires careful renal function monitoring.
Risk Management: Careful administration and monitoring of electrolytes and serum osmolality are crucial to prevent adverse effects like central pontine myelinolysis (HTS) or acute kidney injury (mannitol).

Understanding the Mechanism of Hyperosmolar Therapy

Hyperosmolar therapy operates on the principles of osmosis, the movement of water across a semi-permeable membrane from an area of lower solute concentration to an area of higher solute concentration. In the clinical setting, osmotherapy involves administering a substance that remains primarily within the bloodstream, increasing its solute concentration and raising serum osmolality. This creates an osmotic gradient between the blood and the fluid-filled spaces of the body, such as edematous brain tissue. Water is then drawn out of the brain parenchyma and into the intravascular space, reducing brain swelling and lowering intracranial pressure (ICP).

This mechanism is particularly critical for managing conditions where ICP is elevated. The skull is a rigid compartment containing the brain, blood, and cerebrospinal fluid (CSF). According to the Monroe-Kellie doctrine, any increase in the volume of one of these components must be offset by a decrease in another to prevent a dangerous rise in pressure. Cerebral edema, or brain swelling, increases brain volume and can dangerously elevate ICP, leading to reduced cerebral perfusion and potentially fatal secondary brain injury. Hyperosmolar agents provide a fast-acting solution to reduce this excess fluid.

Primary Example: Hypertonic Saline (HTS)

Hypertonic saline (HTS) is an intravenous fluid with a sodium chloride concentration higher than normal blood serum (0.9% NaCl). It is a potent hyperosmolar agent, with various concentrations available depending on the clinical need.

HTS decreases ICP through several mechanisms:

Osmotic Effect: It increases plasma osmolality, pulling water out of edematous brain tissue into the circulation.
Plasma Expansion: It expands the intravascular volume, which transiently increases blood pressure and cardiac output.
Rheological Effects: It decreases blood viscosity, improving cerebral blood flow and oxygen delivery to the brain.
Immunomodulatory Effects: Some studies suggest it can reduce inflammation following a brain injury.

HTS is often preferred in patients who are hypotensive or hypovolemic, as its volume-expanding properties can help maintain mean arterial pressure and cerebral perfusion. It is available in concentrations such as 3%, 7.5%, and 23.4%. Higher concentrations (e.g., >3%) typically require administration via a central venous catheter to prevent local tissue damage.

Another Key Example: Mannitol

Mannitol, a sugar alcohol, was historically considered the gold-standard hyperosmolar agent for managing intracranial hypertension. It is still widely used and effective, though its mechanism and side effects differ from HTS.

Mannitol works by:

Osmotic Gradient: Similar to HTS, it creates an osmotic gradient across the blood-brain barrier, drawing fluid from the brain into the intravascular space.
Osmotic Diuresis: It acts as an osmotic diuretic, promoting the excretion of free water and solutes by the kidneys. This effect can lead to a reduction in total body water, potentially causing dehydration and hypotension.

Key considerations for mannitol administration include monitoring serum osmolality and avoiding its use in patients with a history of renal dysfunction. The diuretic effect can also make it a less ideal choice for patients who are already experiencing low blood pressure.

Hypertonic Saline vs. Mannitol: A Comparison


Feature	Hypertonic Saline (HTS)	Mannitol
Mechanism	Osmotic shift, plasma volume expansion, improved rheology.	Osmotic shift, osmotic diuresis, reduced blood viscosity.
Effect on BP	Typically increases or maintains blood pressure due to volume expansion.	Can cause hypotension due to diuretic effect and fluid loss.
Diuretic Effect	Minimal, especially with lower concentrations.	Prominent, leading to free water loss.
Duration of Effect	Can last longer, up to 12 hours depending on concentration and administration.	Shorter-acting, typically lasting 4-6 hours.
Electrolyte Impact	Potential for hypernatremia, hyperchloremia, and hypokalemia.	Minimal direct impact on sodium, but fluid shifts and excretion can affect electrolytes.
Renal Risk	Risks include acute kidney injury (AKI) with high serum sodium levels.	Risks include osmotic nephrosis and AKI, especially with elevated serum osmolality.
Rebound Edema	Lower risk of rebound ICP increase.	Higher risk of rebound ICP increase, particularly after repeated dosing.

Clinical Applications of Hyperosmolar Therapy

Hyperosmolar therapy is a cornerstone of managing acute cerebral edema in various neurocritical care scenarios. It is indicated for a range of conditions, including:

Traumatic Brain Injury (TBI): HTS and mannitol are used to manage increased ICP following severe TBI.
Acute Ischemic Stroke: In cases where large strokes cause significant brain swelling, hyperosmolar therapy can help reduce edema and improve outcomes.
Intracerebral Hemorrhage: Medications like HTS can be used to decrease ICP associated with bleeding in the brain.
Fulminant Hepatic Failure: This condition can lead to severe brain swelling, for which hyperosmolar agents are a standard treatment.
Severe Symptomatic Hyponatremia: In addition to neuro-related issues, hypertonic saline is specifically used to correct severely low serum sodium levels.

Conclusion

Hyperosmolar therapy is a vital component of emergency and critical care medicine, used primarily to manage conditions involving cerebral edema and elevated intracranial pressure. Mannitol and hypertonic saline are the two most common examples, each with distinct pharmacological properties that influence its choice for a specific clinical situation. While both agents work by creating an osmotic gradient to draw fluid out of the brain, their differing effects on blood pressure, diuresis, and electrolytes guide treatment selection. The appropriate choice and careful monitoring of these agents are crucial for optimizing patient outcomes and preventing serious side effects. Continuous research, such as the COBI trial for continuous HTS infusion, continues to refine the best practices for this life-saving intervention. For more detailed information on clinical guidelines, refer to authoritative sources such as the American Association of Critical-Care Nurses (AACN) for evidence-based practice protocols and standards.

AACN Practice Resources

Frequently Asked Questions

The main purpose of hyperosmolar therapy is to reduce cerebral edema (brain swelling) and lower dangerously high intracranial pressure (ICP), which can occur after a traumatic brain injury, stroke, or other neurological events.

Hypertonic saline (HTS) works by increasing the concentration of solutes in the blood, creating an osmotic gradient that pulls excess water from the swollen brain tissue into the bloodstream. This reduces brain volume and, consequently, intracranial pressure.

Yes, mannitol is still widely used to treat cerebral edema, although hypertonic saline has become increasingly common. It has a long history as a gold-standard therapy for reducing intracranial hypertension.

Mannitol is a diuretic and primarily works by pulling fluid from the brain and promoting its excretion through the kidneys, which can lead to hypotension. Hypertonic saline increases blood volume and typically helps maintain or increase blood pressure while pulling fluid from the brain.

Risks include electrolyte imbalances (like hypernatremia or hyperchloremia with HTS), volume overload, potential for acute kidney injury (AKI), and rebound edema if therapy is stopped abruptly or administered incorrectly.

Hyperosmolar therapy can be less effective if the blood-brain barrier is significantly disrupted, allowing the hyperosmolar agents to leak into the brain tissue rather than staying in the bloodstream to create the osmotic gradient.

Yes, hyperosmolar agents like hypertonic saline are also used to treat severe, symptomatic hyponatremia (dangerously low sodium levels in the blood) by increasing the serum sodium concentration.