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  1. Pharmacology

    1. Mannitol is an osmotically active solute diuretic. Mannitol inhibits water reabsorption at the loop of Henle and the proximal tubule. The increase in urine output usually is accompanied by an increase in solute excretion. In addition, mannitol transiently increases serum osmolality and decreases CSF pressure by creating an osmotic gradient between brain tissue and the vascular compartment. Water moves across this gradient into the blood vessels, lowering the CSF pressure and decreasing intracranial pressure.

    2. Mannitol may reverse the effects of ciguatoxin by inhibiting ciguatoxin-induced opening of sodium channels and reducing cellular excitability. Mannitol may also increase the dissociation of ciguatoxin from its binding sites on cell membranes.

    3. In the past, mannitol was used to induce “forced diuresis” for some poisonings (eg, phenobarbital, salicylate) to enhance their renal elimination, but this use has been abandoned because of lack of efficacy and potential risks (cerebral and pulmonary edema).

  2. Indications

    1. Proposed as a treatment for neurologic and neurosensory manifestations caused by ciguatera poisoning (See Food Poisoning: Fish and Shellfish).

    2. Possible adjunctive agent in treating severe vitamin A toxicity associated with increased intracranial pressure (pseudotumor cerebri).

    3. Sometimes used as an adjunct to fluid therapy for acute oliguria resulting from massive rhabdomyolysis (See Rhabdomyolysis).

  3. Contraindications

    1. Severe dehydration.

    2. Acute intracranial bleeding.

    3. Pulmonary edema.

    4. Anuria associated with severe renal disease.

  4. Adverse effects

    1. Mannitol may cause excessive expansion of the intravascular space when administered in high concentrations at a rapid rate. This may result in congestive heart failure and pulmonary edema.

    2. Mannitol causes movement of intracellular water to the extracellular space and can produce both transient hyperosmolality and hyponatremia. Generalized electrolyte disturbances may also be seen.

    3. Oliguric or anuric renal failure has occurred in patients receiving mannitol. Low-dose mannitol appears to result in renal vasodilating effects, whereas high doses (>200 g/d) may produce renal vasoconstriction.

    4. Use in pregnancy. FDA Category C (indeterminate). This does not preclude its acute, short-term use in a seriously symptomatic patient (See Introduction in Section III).

  5. Drug or laboratory interactions. Diuresis may result in decreased potassium and magnesium levels, which may increase the risk for QT prolongation in patients taking drugs such as sotalol and droperidol.

  6. Dosage and method of administration

    1. Ciguatera poisoning. Recommended dose is 1 g/kg administered IV over 30–45 minutes. Reportedly most effective when given within 1–2 days of exposure, but case reports describe alleged benefit up to 8 weeks after exposure. Ciguatera poisoning may be accompanied by dehydration, which must be treated with intravenous fluids before the administration of mannitol.

    2. Vitamin A–induced pseudotumor cerebri. Give 0.25–1 g/kg intravenously.

  7. Formulations

    1. Parenteral. Mannitol 10% (500 mL, 1000 mL); 15% (150 mL, 500 mL); 20% (250 mL, 500 mL); 25% (50-mL vials and syringes).

    2. Suggested minimum stocking levels to treat a 100-kg adult for the first 8 hours and 24 hours: mannitol, first 8 hours: 100 g or one bottle (20% mannitol, 500 mL each); first 24 hours: 100 g or one bottle (20% mannitol, 500 mL each).

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