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
- CEN: HEENT EmergenciesEye trauma: Hyphema: Layered blood in the anterior chamber: Head up 30 to 45 degrees, shield, IOP checks, sickle screen: NSAIDs, aspirin; acetazolamide or mannitol in sickle disease or trait
- DKA and HHSComplications and nursing monitoring: Cerebral edema: rare in adults (<0.1%), about 30% fatal; more common in children. Report new headache or vomiting after treatment starts, falling LOC, slowing heart rate or incontinence at once. Mannitol or hypertonic saline treats it.
- GI Bleeding, Liver Failure and PancreatitisAcute liver failure: causes, prognosis and transplant: Astrocytes turn ammonia into glutamine and swell; intracranial hypertension developed in 55% of patients with arterial ammonia above 200 µmol/L (Bernal 2007). Intubate at grade 3; keep HOB 30°, PaCO₂ 34–42 mm Hg and normothermia, check glucose every 1–2 h, and start CRRT early. Murphy 2004 held sodium at 145–155 mmol/L with hypertonic saline;
- Meningitis and EncephalitisReading the CSF: Tuberculous meningitis evolves over days to weeks with cranial nerve palsies, basal enhancement, hydrocephalus and infarcts; it needs 2 months of four drugs, then 7–10 months of isoniazid and rifampin, plus dexamethasone or prednisolone tapered over 6–8 weeks (ATS/CDC/IDSA 2016). Cryptococcal meningitis in advanced HIV or transplant recipients raises opening pressure: with symptom
- Sleep Medicine and Chronic Lung CareCystic fibrosis outpatient care: Inhaled mannitol: Adults; tolerance test first; SABA 5–15 min before each dose
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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 the order, the label and your institution's protocols.