Mannitol (Osmitrol, Resectisol)

Indications

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

Clinical Scenarios
- Fulminant Hepatic Failure with Development of Cerebral Edema (see Fulminant Hepatic Failure, Fulminant Hepatic Failure)
- Large Ischemic Cerebrovascular Accident (CVA) with Development of Cerebral Edema (see Ischemic Cerebrovascular Accident, Ischemic Cerebrovascular Accident)
- Traumatic Brain Injury (TBI) (see Traumatic Brain Injury, Traumatic Brain Injury)
Administration
- Intravenous Mannitol Administration

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

Intravesical Mannitol Administration

Contraindications

Systemic

Active Intracranial Hemorrhage: except during craniotomy
Congestive Heart Failure (CHF) (see Congestive Heart Failure, Congestive Heart Failure)
Pulmonary Edema (see Pulmonary Edema, Pulmonary Edema)
Severe Dehydration/Hypovolemia (see Hypovolemic Shock, Hypovolemic Shock)
Severe Renal Disease/Anuria (see Acute Kidney Injury, Acute Kidney Injury and Chronic Kidney Disease, Chronic Kidney Disease)

Genitourinary Irrigation

Anuria (see Anuria, Anuria)

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

MD Nexus