Osmotic Diuretics

Osmotic diuretics are freely filtered, poorly reabsorbed solutes that hold water in the tubule lumen and in the extracellular space. They lower intracranial and intraocular pressure and increase urine flow, and are used for raised intracranial pressure, acute angle-closure glaucoma and selected kidney protection indications.

Members. Mannitol (intravenous), glycerol and isosorbide (oral, ophthalmic use), and urea (obsolete). Hypertonic saline serves the same role for raised intracranial pressure but is not a diuretic.

Mechanism. Mannitol raises plasma osmolality, drawing water out of brain tissue, the vitreous and cells into the extracellular space. In the kidney it increases tubular flow and reduces medullary tonicity, impairing water reabsorption in the proximal tubule and loop of Henle. Initial plasma volume expansion precedes diuresis.

Cerebral effects. Improved blood rheology and reduced haematocrit may lower intracranial pressure within minutes, and osmotic effect peaks within 15 to 30 minutes and lasts 2 to 6 hours.

Pharmacokinetics. Mannitol is not metabolised and is excreted by the kidney, with a half-life of 100 minutes in normal renal function and much longer in renal failure. Crystallisation occurs at low temperature in concentrated solutions, so an in-line filter is advised.

• Mannitol: 20% solution intravenously; most widely used.
• Glycerol, isosorbide: oral options for glaucoma, with glycerol raising glucose.
• Hypertonic saline (3% to 23.4%): alternative for raised intracranial pressure in hypovolaemia or hyponatraemia.

• Raised intracranial pressure or impending herniation: mannitol 0.25 to 1 g/kg intravenously over 15 to 30 minutes, repeated every 4 to 6 hours if needed, while keeping serum osmolality at 320 mOsm/kg or under. Use as a bridge to definitive treatment.
• Acute angle-closure glaucoma: mannitol 1 to 2 g/kg intravenously over 30 to 60 minutes where other treatments fail, or oral glycerol.
• Prophylaxis of kidney injury: mannitol 12.5 to 25 g during surgery with a risk of rhabdomyolysis or pigment nephropathy, with limited evidence.
• Selection: use hypertonic saline in hypotension or hyponatraemia. Avoid repeated mannitol in kidney failure.

Contraindications. Anuria, established kidney failure that does not respond to a test dose, pulmonary oedema or severe heart failure, severe dehydration, active intracranial haemorrhage (except during craniotomy), and progressive kidney or heart failure after starting.

Adverse effects. Initial volume expansion with pulmonary oedema, dilutional hyponatraemia followed by hypernatraemia and hyperosmolality, hypokalaemia or hyperkalaemia, acute kidney injury at high cumulative doses (over 200 g daily or osmolar gap over 55 mOsm/kg), rebound rise in intracranial pressure, headache, nausea, and tissue necrosis if it extravasates.

Interactions. Other nephrotoxic drugs and NSAIDs raise kidney injury risk. Lithium excretion rises. Digoxin toxicity with hypokalaemia.

Monitoring. Serum sodium, potassium and osmolality (stop above 320 mOsm/kg), osmolar gap, urine output, blood pressure and neurological state.

Referral and escalation. Rising intracranial pressure, falling urine output or pulmonary oedema needs urgent senior and neurosurgical or critical care review.

Special groups. Children: 0.25 to 1 g/kg intravenously. Older adults: higher risk of renal injury. Pregnancy: use only when essential. Renal impairment: avoid unless a response to a test dose is shown.