Osmotic therapy
Mannitol
Indications
- Raised ICP and cerebral edema, including impending herniation and brain relaxation during craniotomy (label)
- Raised intraocular pressure, such as acute angle-closure glaucoma (label)
- Cerebral edema in pediatric DKA, as an alternative to 3% saline (ISPAD 2022)
Dosing
| Where | Dose |
|---|---|
| Seizures and neuro | Mannitol: 0.5–1 g/kg of 20% over 10–20 min; hold if osmolality over 320 or osmolar gap over 20 |
On the quick cards
Mechanism of action
Mannitol is an inert sugar alcohol that stays extracellular, is filtered freely and is barely reabsorbed, so in the proximal tubule and descending limb it holds water by osmosis and raises urine flow and sodium excretion (osmotic diuresis). An intact blood–brain barrier largely excludes it (reflection coefficient about 0.9), so the higher plasma osmolality draws water out of brain tissue. Within minutes it also expands plasma volume and lowers blood viscosity; where autoregulation is intact, cerebral arterioles constrict, reducing cerebral blood volume and ICP.
Pharmacology
- CNS: lowers ICP within minutes and dehydrates brain over 15–30 min, for about 1.5–6 h; also lowers intraocular pressure
- CNS: repeated doses can leak through a damaged barrier and pull water back in (rebound edema)
- Cardiovascular: first expands plasma volume (pulmonary edema risk in heart failure), then the diuresis can cause hypovolemia and hypotension
- Renal: loses sodium, potassium, magnesium, phosphate and free water; high levels injure proximal tubules (osmotic nephrosis)
- Metabolic: early dilutional hyponatremia, later hypernatremia; high or low potassium (label)
Pharmacokinetics
| Onset | ICP begins to fall within minutes; osmotic effect over 15–30 min |
|---|---|
| Duration | About 1.5–6 h; ICP can rebound hours later (label) |
| Half-life | 0.5–2.5 h; about 36 h in kidney failure (label) |
| Distribution | Extracellular within 20–40 min; Vd about 17 L (label) |
| Protein binding | Negligible |
| Metabolism | Only a small fraction (label) |
| Clearance | 87–109 mL/min, close to GFR (label) |
| Elimination | Unchanged in urine, about 80% within 3 h (label) |
| Osmolar gap | Measured osmolality includes mannitol but the calculated value does not, so the gap tracks circulating mannitol; redose when it falls below about 20 |
| Dialysis | Removed by hemodialysis and peritoneal dialysis (label) |
Chemistry
- D-mannitol (C₆H₁₄O₆, MW 182.2), a six-carbon sugar alcohol made by reducing dextrose (label); an isomer of sorbitol
- Not ionized at any body pH; very water-soluble but almost insoluble in lipid, so it stays out of cells and the intact brain
- 20% bags (1,098 mOsm/L) and 25% vials (12.5 g/50 mL, 1,372 mOsm/L); pH 4.5–7.0 (labels)
- Supersaturated at 25% and near saturation at 20% (solubility about 216 g/L, PubChem), so it crystallizes in the cold: warm to redissolve (bags to 70 °C, vials in a 60–80 °C bath), cool, and give through a final in-line filter (labels)
- Can falsely lower phosphate and falsely raise ethylene glycol on some assays (label)
Adverse effects and cautions
In the one-pagers
- Neuro: ICP and StrokeEVD care and osmotic therapy: Mannitol: 0.25–1 g/kg IV bolus: Filter; diuresis, low BP, kidneys, osmolality
- Trauma: Primary and Secondary SurveyBrain and spinal cord injury in the first hours: Herniation: mannitol or hypertonic saline, CT and neurosurgery
- ABG Interpretation in 6 StepsAnion gap, delta-delta and other gaps: The osmolar gap finds uncharged toxins. Calculated osmolality = 2 × Na⁺ + glucose ÷ 18 + BUN ÷ 2.8 (+ ethanol ÷ 3.7); the gap, measured minus calculated, is normally under 10 mOsm/kg (Berend 2014). Na⁺ 140, glucose 90 and BUN 14 give 290; a measured 320 is a gap of 30. Early after methanol or ethylene glycol the osmolar gap is high and the anion gap normal; a
- Electrolyte ImbalancesHypernatremia and the free water deficit: Hypernatremia is always hypertonic and nearly always a water deficit in someone who cannot drink. ICU causes: fever, osmotic diuresis (glucose, mannitol, high-protein feeds), loop diuretics, lactulose and sodium loads (bicarbonate, hypertonic saline).
- Pediatric Assessment and EmergenciesDKA, cerebral edema and status epilepticus: Clinically apparent cerebral injury occurs in 0.5–0.9% of episodes with 21–24% mortality, usually within 12 hours of starting treatment (ISPAD 2022), and PECARN FLUID found that neither saline strength nor infusion rate changed it. Headache, renewed vomiting, a falling heart rate, rising blood pressure or falling consciousness suggest cerebral edema; tre
- Toxins, Stings and Anaphylaxis in the FieldMarine toxins in detail: Ciguatera (CDC Yellow Book 2026): large reef carnivores such as barracuda, grouper, amberjack and moray eel. Symptoms usually start 3-6 hours after the meal (up to 30): diarrhea, vomiting and cramps, then paresthesias, aching or loose-feeling teeth and temperature reversal (cold feels hot), which is characteristic but not always present. Bradycardia, heart block and hypote
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Sources
- FDA label: Osmitrol (Baxter, 2025)
- FDA label: Mannitol 25% (Fresenius Kabi, 2022)
- NCS cerebral edema guideline (Cook 2020)
- PubChem: mannitol
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.