Mannitol (Osmitrol, Resectisol)

Indications

Treatment of Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure, Increased Intracranial Pressure): intravenous mannitol administration

Trans-Urethral Resection of the Prostate (TURP) (see Benign Prostatic Hypertrophy, Benign Prostatic Hypertrophy)

  • Intravesical Mannitol Administration

Contraindications

Systemic

Genitourinary Irrigation


Pharmacology

Mannitol is an Osmotic Diuretic

  • Mannitol Increases the Osmotic Pressure of Glomerular Filtrate, Inhibiting Tubular Resorption of Water/Electrolytes and Increasing Urine Output
  • Treatment of Increased Intracranial Pressure (see Increased Intracranial Pressure, Increased Intracranial Pressure)
    • Mechanism: unclear
      • Mannitol May Decrease Blood Viscosity, Increasing Blood Flow and Oxygen Transport
      • Mannitol May Cause Vasoconstriction of the Pial Arteries, Decreasing Cerebral Blood Volume and Intracranial Pressure
      • Mannitol May Cause Enhancement of Withdrawal of Water from Brain Parenchyma (and Enhancement of Urinary Water Excretion)
    • With Continuous Infusion, Mannitol May Accumulate in the Brain (Resulting in Rebound Increases in Intracranial Pressure): for this reason, intermittent dosing is preferred when treating increased intracranial pressure

Pharmacokinetics

  • Onset of Action
    • Onset of Decrease in Intracranial Pressure: 15-30 min
    • Onset of Diuresis: 1-3 hrs
  • Duration of Action
    • Duration of Decrease in Intracranial Pressure: 1.5-6 hrs
  • Elimination Half-Life: 0.25-1.7 hrs
    • Elimination Half-Life in the Setting of Renal Failure: 6-36 hrs

Metabolism

  • Minimal Hepatic Metabolism to Glycogen
  • Approximately 55-87% is Excreted in Urine as Unchanged Drug

Administration

IV (Treatment of Increased Intracranial Pressure) (see Increased Intracranial Pressure, Increased Intracranial Pressure)

  • Dose: 0.25-1 g/kg (typically, 50g of 20% solution infused over 30-60 min)
    • Repeat q6-8 hrs, as Required
  • Dose to Target Desired Serum Osmolality (see Serum Osmolality, Serum Osmolality)
    • Hold for Serum Osm >310 mOsm/L
      • Alternatively, May Target an Osmolal Gap <18-20
  • Infusion Considerations
    • Inspect for Crystals Prior to Infusion: may need to resolve by warming
    • Do Not Infuse with Packed Red Blood Cells: mannitol may result in crenation or agglutination of red blood cells
    • Vesicant (at Concentrations >5%): avoid extravasation
      • Management of Extravasation
        • Stop Mannitol Infusion and Disconnect (Leaving Cannula in Place)
        • Aspirate Extravasated Solution (without Flushing the Line)
        • Intradermal or Subcutaneous Hyaluronidase (see Hyaluronidase, Hyaluronidase): using 25-gauge needle and 15 U/mL solution, inject five separate 0.2-0.3 mL injections (total = 1-1.7 mL injected) into the leading edge of extravasation site in clockwise direction
        • Apply Dry Cold Compress to Site

Dose Adjustment

  • Hepatic: no dose adjustment is necessary
  • Renal: mannitol is contraindicated in the setting of severe renal impairment

Use in Pregnancy (see Pregnancy, Pregnancy)

  • Unknown Safety, as Studies Have Not Been Conducted in this Setting

Use in Lactation

  • Unknown if Mannitol is Excreted into Breast Milk: caution should be exercised when used in this setting

Drug Interactions

  • Aminoglycosides (see Aminoglycosides, Aminoglycosides): systemic mannitol may increase the nephrotoxicity of aminoglycosides (risk: X -> avoid combination)
  • Opiates (see Opiates, Opiates): opiates may increase the adverse/toxic effects of diuretics and the therapeutic effects of diuretics (risk: C -> monitor therapy)

Adverse Effects

Renal Adverse Effects

  • Acute Kidney Injury (AKI) (see Acute Kidney Injury, Acute Kidney Injury)
    • Epidemiology: may occur with high doses
    • Physiology: acute renal tubular damage
    • Prevention: maintain serum osmolality <320 mOsm/L
  • Diuresis
    • Clinical
      • Hypovolemia
      • Electrolyte Depletion
  • Elevated Osmolal Gap without Anion Gap Metabolic Acidosis (see Serum Osmolality, Serum Osmolality)
  • Pseudohyponatremia (see Hyponatremia, Hyponatremia)
    • Physiology: due to mannitol being an osmotically-active solute, water is pulled out of cells, resulting in dilution of serum sodium

Other Adverse Effects

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Adverse Reactions (Frequency not defined):
Cardiovascular: Chest pain, cardiac failure, hypertension, hypotension, local thrombophlebitis, peripheral edema, tachycardia
Central nervous system: Chills, dizziness, headache, seizure
Dermatologic: Bullous rash, urticaria
Endocrine & metabolic: Dehydration (secondary to rapid diuresis), dilutional hyponatremia, electrolyte disturbance (increased osmolar gap), fluid and electrolyte disturbance, hypovolemia (secondary to rapid diuresis), hyperglycemia, hyperkalemia (hyperosmolality-induced), hypernatremia, hypervolemia, metabolic acidosis (dilutional), water intoxication
Gastrointestinal: Nausea, vomiting, xerostomia
Genitourinary: Dysuria
Hypersensitivity: Hypersensitivity reaction
Local: Local pain
Ophthalmic: Blurred vision
Renal: Acute renal failure, tubular necrosis (adult dose: >200 g/day; serum osmolality >320 mOsm/L), polyuria
Respiratory: Pulmonary edema, rhinitis
Miscellaneous: Fever, tissue necrosis


References

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