Mannitol (Osmitrol)

Hyperosmolar agent used primarily for rapid reduction of elevated intracranial pressure (ICP) or impending herniation, and occasionally for short-term reduction of intraocular pressure or as part of forced diuresis strategies.

• Typical adult dose for suspected herniation / significantly elevated ICP: 0.5–1 g/kg IV bolus of 15–25% mannitol over 15–20 minutes. Dosing ranges in guidelines are generally 0.25–1 g/kg IV; many neurocritical care practices favor 0.5–1 g/kg bolus dosing rather than frequent small doses
• Onset for ICP reduction: Within minutes; peak effect around 20–40 minutes; duration roughly 2–6 hours, depending on renal function and blood–brain barrier (BBB) integrity
• Monitoring is critical: Watch serum osmolality (often keep ≤ 320 mOsm/kg), osmolar gap, electrolytes, volume status, and renal function. Avoid repeat dosing if osmolality is high or patient becomes hypotensive or oliguric
• Current trends: Many neurocritical care centers increasingly favor hypertonic saline over mannitol for routine osmotherapy, but mannitol remains a recognized rescue therapy for malignant cerebral edema and impending herniation

• Generic Name: Mannitol
• Brand Names: Osmitrol, Resectisol, various generics

Osmotic diuretic; hyperosmolar agent for intracranial pressure (ICP) and intraocular pressure (IOP) reduction

• Emergency ICP reduction with signs of herniation or significant neurologic deterioration (e.g., fixed/dilated pupil, decerebrate posturing, rapidly worsening exam)
• Intraocular pressure (IOP) reduction in acute angle-closure glaucoma or perioperative ophthalmic surgery settings when other therapies are inadequate or unavailable
• Osmotic diuresis in selected scenarios (e.g., intraoperative neuroprotection, some protocols for rhabdomyolysis or renal protection); evidence is variable and practice is evolving
• Traumatic brain injury (TBI): Historically used for severe TBI-related ICP; contemporary practice frequently favors hypertonic saline as first-line osmotherapy, but mannitol remains a recognized agent in many guidelines and protocols

Available Forms:

• IV solutions: commonly 5%, 10%, 15%, 20%, and 25% mannitol in water; 20% (200 g/L) is typical for ICP management
• Unit doses: 20% 500 mL bag (contains 100 g mannitol), 20% 250 mL bag (50 g), and 12.5 g vials or syringes in some institutions
• Solutions may crystallize at cooler temperatures; warm and redissolve crystals completely and inspect before administration; use a filter when required by institutional policy
• Administer via a dedicated IV line or lumen when possible due to hypertonicity

Standard Adult Dosing:

Absolute Contraindications:

• Anuria due to severe renal disease (risk of accumulation and pulmonary edema)
• Severe hypovolemia or hypotension (risk of hemodynamic collapse after osmotic diuresis)
• Severe pulmonary edema or decompensated heart failure (risk of fluid shifts and worsening pulmonary congestion)
• Known hypersensitivity to mannitol

Major Precautions:

• Renal impairment or oliguric states: May precipitate or worsen AKI; monitor urine output and renal function closely
• Electrolyte disturbances: Can cause hyponatremia, hypernatremia, or hyperkalemia depending on timing and renal handling; monitor serum electrolytes and osmolality
• Rebound ICP: Avoid repeated dosing without adequate clearance and in patients with severely disrupted BBB
• Heart failure or pulmonary disease: Monitor for fluid overload and pulmonary edema, especially when large doses are used
• Pregnancy: Use with caution; weigh maternal neurologic benefits against limited fetal safety data

Common / Important:

• Polyuria and volume depletion
• Headache, nausea, vomiting
• Local irritation or thrombophlebitis at infusion site

Serious:

• Hypotension and hemodynamic collapse in volume-depleted or shock states
• Acute kidney injury or renal failure, especially with pre-existing renal disease or repeated high doses
• Pulmonary edema and heart failure due to rapid volume shifts or accumulation in renal impairment
• Electrolyte derangements (e.g., hypernatremia or hyponatremia, hyperkalemia)
• Rebound intracranial hypertension and worsening cerebral edema in cases of BBB disruption or excessive cumulative dosing

Clinical Monitoring:

• Frequent neurologic assessments and ICP measurements when available
• Blood pressure, heart rate, and MAP (preferably via arterial line in unstable patients)
• Urine output (goal often ≥0.5–1 mL/kg/h) and daily weights
• Chest exam, oxygenation, and imaging as needed to assess for pulmonary edema or volume overload

Laboratory Monitoring:

• Serum electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻), BUN/creatinine, serum osmolality, and osmolar gap

• Osmotic properties: Mannitol is a small, osmotically active sugar alcohol filtered at the glomerulus and minimally reabsorbed in the renal tubules, producing osmotic diuresis
• ICP reduction: By increasing plasma osmolality, mannitol creates an osmotic gradient between intravascular and intracellular compartments, drawing water out of brain parenchyma (and other tissues) into the intravascular space, thereby decreasing brain volume and ICP when the BBB is intact
• Hemodynamic effects: The intravascular volume expansion can transiently improve cerebral perfusion pressure (CPP), but diuresis ultimately reduces intravascular volume; net effect depends on baseline hemodynamics and dose
• Rebound risk: If the BBB is severely disrupted, mannitol may enter brain tissue and eventually draw water back into injured areas, potentially causing rebound cerebral edema with repeated dosing or high serum levels
• Renal mechanism: Renally, mannitol increases tubular fluid osmolality, limiting water reabsorption and producing osmotic diuresis; this can improve urine flow but also predispose to volume depletion and electrolyte abnormalities

Pharmacokinetics:

• Route: Given IV as a hypertonic solution (commonly 5%, 10%, 15%, 20%, or 25%); 20% mannitol is most frequently used for ICP management in ED/ICU
• Onset (ICP effect): Minutes; peak effect usually 20–40 minutes post-bolus; clinical duration 2–6 hours depending on renal clearance and BBB status
• Distribution: Largely confined to the extracellular space; does not freely cross the intact BBB, but can accumulate in injured brain tissue
• Metabolism: Not significantly metabolized; pharmacologic effect is from the intact mannitol molecule
• Elimination: Primarily renal excretion via glomerular filtration; elimination half-life typically 0.5–2 hours in patients with normal renal function and volume status; markedly prolonged in renal failure
• Renal impairment: In renal impairment or oliguria, mannitol can accumulate, causing a hyperosmolar state, volume overload, and risk of heart failure or pulmonary edema

• 1. Kim, J. H., Lee, H. K., & Lee, J. H. (2023). Optimizing mannitol use in managing increased intracranial pressure. Journal of Neurocritical Care, 16(1), 1–12. https://doi.org/10.18700/jnc.2023.16.1.1
• 2. LITFL. (2024). Mannitol – CCC Pharmacology. Life in the Fast Lane. https://litfl.com/mannitol/
• 3. Brain Trauma Foundation. (2007). Guidelines for the management of severe traumatic brain injury (3rd ed.). Journal of Neurotrauma, 24(Suppl 1), S1–S106. https://doi.org/10.1089/neu.2007.9999
• 4. May, C. C. (2020). Treatment of elevated intracranial pressure. In Critical Care Self-Assessment Program (CCSAP). American College of Clinical Pharmacy.
• 5. Weingart, S. (2022). Elevated intracranial pressure (IBCC). EMCrit Project. https://emcrit.org/ibcc/icp/