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Introduction

  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 cerebrospinal fluid (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 is purported to reverse the effects of ciguatoxin by various mechanisms: inhibiting ciguatoxin-induced opening of sodium channels; decreasing neuronal edema; acting as a scavenger of ciguatoxin-generated free radicals; reducing cellular excitability; and increasing the dissociation of ciguatoxin from its binding sites on cell membranes.
    3. Historically, mannitol was used to induce “forced diuresis” for some poisonings (eg, phenobarbital, salicylate) to enhance renal elimination, but has since been abandoned due to lack of efficacy and potential risks of cerebral and pulmonary edema.
  2. Indications
    1. Proposed as a treatment for neurologic and neurosensory manifestations caused by ciguatera poisoning. However, a double-blind, randomized study found that mannitol was not superior to normal saline in relieving signs or symptoms of ciguatera fish poisoning.
    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.
  3. Contraindications
    1. Severe dehydration.
    2. Acute intracranial bleeding.
    3. Pulmonary edema.
    4. Congestive heart failure.
    5. 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 (Introduction).
  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 known to prolong the QT.
  6. Dosage and method of administration
    1. Ciguatera poisoning. Recommended dose is 0.5-1.0 g/kg administered IV over 30-45 minutes. Reportedly most effective when given within 24-72 hours of onset of symptoms or exposure, but case reports describe alleged benefit up to several 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 over 30 minutes and repeat every 4-6 hours as needed.