Mannitol
Osmotic diuretic in neurosurgery, glaucoma and inhalation
Mannitol is a hexahydric sugar alcohol used in medicine as an osmotically active diuretic. The intravenous preparation (typically 15 or 20 percent) is used for intracranial pressure reduction in neurosurgery and emergency medicine, for relief in acute angle closure glaucoma and for promoting diuresis in certain poisonings. Inhaled mannitol is available as a bronchial provocation test and as a mucolytic therapy in cystic fibrosis (Bronchitol). As a bulking agent it is also present in many tablet formulations.
As an osmotic diuretic, mannitol has a very specific profile that differs markedly from loop diuretics such as furosemide. It draws water from the intracellular space into the plasma, lowers intracranial and intraocular pressure and simultaneously increases urine output. Administration takes place almost exclusively in the inpatient setting and requires close clinical monitoring of electrolytes, fluid balance and renal function.
Mechanism of Action
After intravenous administration mannitol is not metabolised, not reabsorbed and only glomerularly filtered. In the plasma it osmotically raises the pressure and water shifts from the tissues, particularly the brain and the vitreous body, into the intravascular compartment. Intracranial pressure falls, cerebral perfusion pressure improves and cerebral oedema decreases.
In the kidney mannitol passes the glomerulus but is not tubularly reabsorbed. In the tubular lumen it osmotically retains water, and urine production rises markedly. At the same time, excretion of sodium, potassium and hydrogen ions increases. In poisonings with certain water soluble substances this supports renal elimination.
In airway application, mannitol acts osmotically on the bronchial mucosa. Water is drawn into the viscous secretions of patients with cystic fibrosis or bronchiectasis, rheological properties of the secretions improve and mucociliary clearance rises. As a provocation test, inhalation triggers bronchoconstriction in hyperreactive airways, which is used in asthma diagnostics.
Indications
- Raised intracranial pressure after traumatic brain injury, cerebral oedema, ischaemic stroke, intracranial bleeding or tumours
- Acute angle closure glaucoma for rapid reduction of intraocular pressure, often in the emergency department
- Perioperative therapy in neurosurgery for brain relaxation and better access
- Forced osmotic diuresis in certain intoxications, rhabdomyolysis and transfusion related haemolysis (indication now restricted)
- Cystic fibrosis as inhaled mucolytic (Bronchitol) for long term secretolytic therapy
- Bronchial provocation for diagnosis of airway hyperreactivity and asthma
- Irrigation fluid in urology during transurethral prostate resection, because mannitol is electrolyte free and keeps the electrosurgical loop non conducting
Dosage and Administration
Reduction of intracranial pressure: 0.25 to 1 g per kg body weight as a short intravenous infusion over 15 to 30 minutes. In severe cases the dose can be repeated after 4 to 6 hours, with a maximum daily dose of 2 g per kg. Acute angle closure glaucoma: 1 to 2 g per kg over 30 to 60 minutes.
Inhalation in cystic fibrosis: 400 mg twice daily after an initial test dose to assess bronchoconstriction and under bronchodilator premedication. Bronchial provocation: stepwise dosing according to a standardised protocol.
Renal impairment: caution advised; in anuria or severe renal impairment mannitol is contraindicated because accumulation may trigger a hyperosmolar crisis. Hepatic impairment: no formal dose adjustment. Do not administer infusions containing visible crystals; warm the ampoule to body temperature before use. Serum osmolality monitoring (target serum osmolality no higher than 320 mOsm/kg) guides continuation of therapy.
Side Effects
Common: electrolyte disturbances (hyponatraemia or hypernatraemia depending on the course, hypokalaemia, hypocalcaemia), increased urinary frequency, thirst, headache, nausea, vomiting, visual disturbances.
Uncommon: hypervolaemia and pulmonary oedema particularly in heart failure, hyperosmolar coma, thrombophlebitis at the infusion site, allergic reactions, hypotension after rapid administration.
Rare and clinically relevant: acute kidney injury from osmotic nephrosis at high total doses or with pre existing damage, rebound rise in intracranial pressure with hyperosmolarity or abrupt discontinuation, seizures in severe electrolyte disturbances.
Inhalation: common adverse effects include cough, bronchoconstriction, haemoptysis and oropharyngeal pain. The first dose is therefore given only under medical supervision with a test dose.
Interactions
- Other diuretics (furosemide, thiazides): additive diuresis and electrolyte disturbance, concomitant use only on a clear indication
- Digitalis glycosides: hypokalaemia during mannitol enhances glycoside effect and arrhythmia risk
- Lithium: increased renal elimination, plasma levels may fall
- Nephrotoxic drugs (aminoglycosides, cisplatin, ciclosporin): additive kidney damage
- Potassium chloride or sodium bicarbonate infusions: mannitol must not be mixed with whole blood or electrolyte containing infusions in the same line, precipitation is possible
Special Notes
Contraindications: severe dehydration, anuria, severe renal impairment without response to a test dose, decompensated heart failure, existing pulmonary oedema, active intracranial bleeding with intact brain tissue (assess case by case), known hypersensitivity to mannitol.
Monitoring: fluid balance, urine output, serum sodium, potassium, creatinine, osmolality and central venous pressure at high doses. In intensive care, regular clinical reassessment (GCS, pupils, intracranial pressure) guides therapy.
Pregnancy and breastfeeding: use only on a vital indication, for example in neurosurgical emergencies. Specific data in pregnancy are lacking. Inhaled Bronchitol: strict patient selection, clinically stable adults from age 18 with cystic fibrosis, initial test dose needed because of bronchoconstriction risk.
Crystallisation: at room temperature below 20 degrees, mannitol tends to precipitate. The ampoule or bottle must be warmed to body temperature before use; visible crystals mean the solution must be discarded.
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Frequently Asked Questions
Why is mannitol used in raised intracranial pressure?
Mannitol osmotically draws water from the brain into the bloodstream. Intracranial pressure falls within minutes, cerebral perfusion improves and cerebral oedema decreases. The effect is time limited, so mannitol is a bridging therapy until definitive measures such as surgery or ventricular drainage can be performed.
Why does mannitol crystallise in the ampoule?
Mannitol has limited solubility at room temperature. If the ampoule is stored too cold, crystals form. Before use, these must be redissolved by warming the ampoule in a water bath to 37 degrees. Solutions with visible crystals must not be infused because they could cause microembolism.
Is mannitol still used in glaucoma therapy?
Yes, in acute angle closure glaucoma, together with topical medications and acetazolamide. Intravenous mannitol infusion lowers intraocular pressure within minutes and buys time until definitive therapy. It plays no role in chronic therapy, for which prostaglandins, beta blockers and other eye drops are used.
What is Bronchitol?
Bronchitol is an inhaled mannitol formulation for long term therapy of cystic fibrosis in adults. Inhalation draws water into the viscous bronchial mucus, facilitates expectoration and improves lung function. The first dose is given under medical supervision because some patients react with bronchoconstriction.
Sources
- EMA, Bronchitol (Mannitol) EPAR
- AWMF, Guidelines on Traumatic Brain Injury and Stroke
- Gelbe Liste, Mannitol active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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