ADMINISTRATION ROUTES:
IV
ALTERNATIVE NAMES:
Osmitrol
ICU INDICATIONS:
- Cerebral oedema causing raised intracranial pressure
- Raised intra-ocular pressure
Oral mannitol has also been used (together with activated charcoal) as an osmotic agent to increase intestinal removal of poisons
PRESENTATION AND ADMINISTRATION:
I/V:
| Solution | Volume of bag (mL) | Amount of mannitol in bag | Osmolality (mOsmol/kg) | pH |
|---|---|---|---|---|
| 10% | 1000 | 100 g | 550 | 5.5 |
| 20% | 500 | 100 g | 1100 | 5.0 |
Mannitol may crystallise when exposed to low temperatures. This risk is increased with the 20% solution. The solution should be inspected prior to administration. If crystals are visible, they can be redissolved by warming whilst agitating. Check for crystals again on cooling prior to administration.
Mannitol is incompatible with blood transfusions and some antibiotics (including cefepime, imipenem and cilastatin). Risk of precipitation if potassium or sodium chloride is added.
Administer through in-line filter; do not use in-series connections.
Due to risk of thrombophlebitis, mannitol should be administered via a large peripheral or central vein where possible.
DOSAGE:
I/V:
Initial dose:
0.5 - 1 g/kg of 10–20% solution over 15–30 min by infusion
Effects occur within 15 - 30 mins and last 4-6 hrs
Subsequent dose:
0.25 – 0.5 g/kg may follow QID for 24 hrs unless diuresis has not occurred, cardiovascular instability ensues or plasma osmolality exceeds 315 mOsmol/kg
The table below shows the volume (in mL) of 20% mannitol to be administered for a dose of 0.5 g/kg (100 mL of 20% solution = 20 g):
| Patient weight (kg) | Volume of 20% mannitol at 0.5 g/kg (mL) |
|---|---|
| 60 | 150 |
| 70 | 175 |
| 80 | 200 |
| 90 | 225 |
| 100 | 250 |
| 110 | 275 |
| 120 | 300 |
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Patients with pre-existing renal disease are at increased risk of renal failure. Mannitol is contraindicated in severe renal impairment. It will not induce diuresis in normally anuric patients. Reversible, acute renal failure has occurred in patients with previously normal renal function who receive large intravenous doses of mannitol.
DOSAGE IN PAEDIATRICS:
Cerebral oedema or raised intra-ocular pressure:
Give as IV infusion over 30 - 60 mins
Neonates:
0.25 - 0.5 g/kg/dose
1 month - 12 years:
0.25 – 1.5 g/kg/dose
Repeat if necessary 1-2 times after 4-8 hours
12 - 18 years:
0.25 - 2 g/kg/dose
Repeat if necessary 1-2 times after 4-8 hours
Peripheral oedema and ascites:
Give as IV infusion over 2 - 6 hours
1 month - 18 years:
1 - 2 g/kg
CLINICAL PHARMACOLOGY:
Mannitol is a plant-derived alcohol that acts as an osmotic diuretic by drawing water from extracellular and intracellular spaces into the vascular compartment. Relatively small amounts are metabolised but it is not reabsorbed once filtered in the kidneys and continues to be osmotically active in the urine, causing diuresis. Efficacy in cerebral oedema depends on integrity of the blood–brain barrier that may be altered in neurological disease, although some benefit is derived from the systemic dehydration it produces. It may also act as a free radical scavenger
CONTRAINDICATIONS:
- Hypersensitivity to mannitol
- Severe heart failure
- Severe pulmonary oedema
- Anuric renal failure
- Severe dehydration
- Disturbance of the blood brain barrier
- Shock
- Hyperosmolarity
WARNINGS:
Extravasation causes inflammation and thrombophlebitis. Bullous eruptions and compartment syndrome have also been described
PRECAUTIONS:
General:
Use with caution in severe renal impairment as described above
Laboratory Tests:
Monitor fluid and electrolyte balance, serum osmolality and renal function. Maintain serum osmolality less than 315 mOsmol/kg
Drug/Laboratory Test Interactions:
May cause false positive results in tests for blood ethylene glycol. Response to lithium and methotrexate may be impaired due to increased urinary excretion
Pregnancy:
No safety data are available - avoid unless essential
Nursing Mothers:
Compatible with breast feeding
IMPORTANT DRUG INTERACTIONS IN ICU:
Other diuretics potentiate the effects of mannitol. Dose adjustment may be required
Increased risk of nephrotoxicity with cyclosporin.
Potentiation of ototoxic effects of aminoglycosides.
Enhances effects of depolarising muscle relaxants.
Decreased effect of oral anti-coagulants due to increased concentration of clotting factors secondary to dehydration.
Increased risk of digoxin toxicity if resultant hypokalaemia is uncorrected.
ADVERSE REACTIONS:
General:
Metabolic acidosis or alkalosis, fluid and electrolyte imbalances including hyper/ hyponatraemia, hyper/hypokalaemia, dry mouth, thirst, chills, fever, urticaria
Cardiovascular System:
Increased vascular volume and CVP may cause cardiac failure, hypotension, hypertension, oedema, arrhythmia, chest pain, palpitations
Respiratory System:
Pulmonary oedema, rhinitis
Renal System:
Dehydration, focal osmotic nephrosis, acute renal failure, fluid and electrolyte imbalance, urinary retention
Neurological System:
Temporarily increases cerebral blood flow. Intracerebral pressure may rise slightly before falling, especially after rapid injection. Excessive brain shrinkage in the elderly may rupture subdural veins. A rebound increase in ICP may occur if treatment is prolonged due to eventual passage of mannitol into cerebral cells. This effect is more likely after repeated dosing. May also cause headache, convulsions, dizziness, blurred vision, confusion, lethargy
Gastro-intestinal System:
Nausea, vomiting, dry mouth, thirst