Mannitol

Mannitol is an osmotic diuretic given by intravenous infusion. It lowers raised intracranial and intraocular pressure and promotes urine flow in selected cases of oliguria. It is not absorbed or metabolised and stays in the extracellular space, so it draws water out of cells. Its main hazards are volume overload, hyperosmolality and kidney injury. It is available in most East African referral hospitals as a 20% solution.

Classification. Osmotic diuretic; sugar alcohol.

Mechanism. Raises plasma osmolality, drawing water out of brain cells, the eye and tissues into the plasma. It is freely filtered and not reabsorbed, so it keeps water in the tubular lumen and increases urine flow (osmotic diuresis).

Pharmacodynamics. Intracranial pressure falls within 15 to 30 minutes of infusion, peak 60 to 90 minutes, duration 3 to 6 hours. Urine flow begins within 1 hour. Transient plasma volume expansion at the start can worsen heart failure.

Pharmacokinetics. Given IV only (oral absorption is minimal and causes diarrhoea). Distributes in the extracellular fluid. Half life 100 minutes (longer in kidney impairment). About 80% excreted unchanged in urine within 3 hours.

Raised intracranial pressure, adult (IV, 20% solution).

• 0.25 to 1 g/kg (1.25 to 5 mL/kg of 20%) over 15 to 30 minutes.

• Repeat every 4 to 6 hours as needed; maximum 2 g/kg in a single day in most settings.

• Keep serum osmolality below 320 mOsm/kg.

Raised intraocular pressure (acute glaucoma), adult. 1.5 to 2 g/kg (7.5 to 10 mL/kg of 20%) over 30 to 60 minutes; give before surgery.

Oliguria (test dose), adult. 200 mg/kg over 3 to 5 minutes; if urine output is under 30 mL/hour in the next 2 hours, do not continue.

Maintenance diuresis (rare), adult. 50 to 100 g over 24 hours; use only with measured fluid balance.

Children. Raised intracranial pressure: 0.25 to 1 g/kg over 20 to 30 minutes; repeat every 4 to 6 hours as needed. Intraocular pressure: 1 to 2 g/kg over 30 to 60 minutes.

Contraindications. Anuria not responding to a test dose; severe pulmonary congestion or pulmonary oedema; progressive heart failure or kidney failure after starting; severe dehydration; intracranial bleeding (except during craniotomy); severe hyponatraemia; hypersensitivity.

Warnings. Expansion of plasma volume, which can cause pulmonary oedema in heart failure; hyperosmolar state; hyponatraemia (dilutional, early) and hypernatraemia (late); acute kidney injury; rebound rise in intracranial pressure; extravasation causing tissue damage. Crystals form in cold solutions.

Adverse effects. Headache, nausea, vomiting, thirst, chills, fluid and electrolyte disturbance, hypotension, tachycardia, rebound intracranial hypertension, kidney injury, seizures.

Interactions. Lithium: increased excretion. Digoxin: hypokalaemia raises toxicity. Aminoglycosides and nephrotoxic drugs: kidney injury risk. Loop diuretics: more electrolyte loss. Other osmotic agents: additive hyperosmolality.

Special groups.

• Pregnancy: use only if essential; no good data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no change.

• Older adults: reduce the dose; high risk of volume and kidney problems.

• Kidney impairment: avoid unless the test dose produces a urine response; limit to a single dose.

• Liver impairment: use with caution; shifts in fluid and sodium.

Formulations. Infusion 10%, 15% and 20% in bags of 100 to 500 mL (20% equals 200 mg/mL).

Administration. IV through a large peripheral or central vein. Use an in-line filter (0.2 micrometres) when crystals are possible. If crystals are present, warm the bag to 37 degrees Celsius and shake before use. Do not give with blood in the same line (clumping).

Baseline. Serum osmolality, sodium, potassium, creatinine and eGFR, volume status, urine output (catheter), neurological score, weight.

Monitoring. Urine output hourly; serum osmolality, sodium and potassium every 6 hours; creatinine daily; neurological state; blood pressure and signs of fluid overload. Stop if osmolality is above 320 mOsm/kg, osmolar gap is above 10 mOsm/kg, urine output falls, or heart failure develops.

Stopping. Do not stop abruptly in a patient with continuing raised pressure; step down and use alternative therapy (for example hypertonic saline) where needed.

Common prescribing errors. Giving it as a repeated bolus without osmolality checks; giving to a patient with pulmonary oedema; failing to place a catheter; mixing the wrong strength (200 mg/mL versus 100 mg/mL); giving cold solution with crystals; using it for intracranial bleeding before surgery.