Acme's Mannitol

Approved Medical Indications:

• Cerebral Edema: For reduction of elevated intracranial pressure associated with cerebral edema.
• Increased Intraocular Pressure (IOP): To reduce acutely elevated IOP before ophthalmologic surgery or during acute glaucoma.
• Promotion of Diuresis: For prevention or treatment of the oliguric phase of acute renal failure.
• Urinary Excretion of Toxins: As an adjunct in treatment of drug toxicity to promote excretion (e.g., salicylates, cisplatin).

Important Off-label or Clinically Accepted Uses:

• Prevention of Acute Kidney Injury (AKI): Occasionally used in high-risk surgeries, although benefit is controversial.
• Contrast-Induced Nephropathy: Previously used; not currently recommended in most guidelines.

Route: Intravenous infusion only.

Adults:

• For cerebral edema / increased ICP:
  0.25 to 2 g/kg IV over 30–60 minutes every 6–8 hours as needed.
  Maximum daily dose: Usually ≤200 g/day.
• For acute glaucoma / elevated IOP:
  1.5 to 2 g/kg IV over 30–60 minutes.
• For diuresis / renal protection:
  Test dose: 200 mg/kg or 12.5 g IV over 3–5 minutes.
  If urine output increases, give 50–100 g IV over 90 minutes.

Pediatrics:

• For cerebral edema / increased ICP or IOP:
  0.25 to 2 g/kg IV over 30–60 minutes. Repeat every 6–8 hours based on clinical need.
• For forced diuresis:
  0.25 to 1 g/kg IV over 30–60 minutes.

Geriatric Patients:

• Use caution due to age-related renal function decline.
• Monitor fluid status, electrolytes, and renal parameters closely.

Special Populations:

• Renal Impairment:
  Contraindicated in established anuria. Use test dose to assess renal response before continuing.
• Hepatic Impairment:
  No specific dose adjustment required, but monitor for fluid and electrolyte imbalance.

Administration Advice:

• Inspect for crystals; warm to 37°C and shake to dissolve before use if needed.
• Infuse with an in-line filter to avoid crystal embolism.
• Monitor serum osmolality, electrolytes, renal function, and fluid balance regularly.

Mannitol is an osmotic diuretic that increases the osmotic pressure of the glomerular filtrate, thereby inhibiting tubular reabsorption of water and electrolytes in the nephron. This results in enhanced urinary output and elimination of excess fluid. Additionally, when administered IV, mannitol increases plasma osmolality, drawing water out of edematous tissues such as the brain and eyes. This action helps reduce intracranial pressure and intraocular pressure. Because mannitol does not cross the intact blood-brain barrier, its osmotic action is effective in pulling water from the central nervous system into the intravascular space.

• Absorption: Not absorbed orally; must be administered IV.
• Distribution: Limited to extracellular fluid; does not enter cells or cross the intact blood-brain barrier.
• Onset of Action:
• Diuresis: Within 1–3 hours
• ICP/IOP reduction: Within 15–30 minutes
• Bioavailability: 100% (IV only)
• Protein Binding: None
• Metabolism: Not significantly metabolized (minimal hepatic metabolism)
• Half-Life: ~100 minutes (prolonged in renal dysfunction)
• Excretion: Excreted unchanged via glomerular filtration in urine

• Pregnancy:
  Former FDA category C. Use only if clearly needed. Animal data do not show teratogenicity, but human data are limited. Rapid plasma expansion may pose risk in preeclamptic patients.
• Lactation:
  Unknown whether mannitol is excreted in breast milk. Given poor oral bioavailability and low systemic risk, it may be used cautiously while breastfeeding. Avoid IV administration near nursing times or pump and discard if concerned.

• Primary Class: Osmotic Diuretic
• Secondary Classifications:
• Intracranial pressure-lowering agent
• Antiglaucoma agent (emergency setting)
• Renal protective adjunct (non-routine)

• Known hypersensitivity to mannitol or excipients
• Established anuria or severe renal impairment without response to test dose
• Active intracranial bleeding (except during craniotomy)
• Severe pulmonary edema or heart failure
• Dehydration
• Serum osmolality >320 mOsm/kg

• Electrolyte Imbalance: Monitor for hyponatremia, hypernatremia, hypokalemia, and hyperkalemia.
• Renal Failure: Risk of osmotic nephrosis and worsening renal function. Monitor urine output and creatinine.
• Pulmonary Edema / CHF: Avoid use in patients with compromised cardiac function due to risk of fluid overload.
• Serum Osmolality: Discontinue if osmolality exceeds 320 mOsm/kg.
• Rebound ICP: Possible with repeated or abrupt discontinuation.
• Crystallization Risk: Inspect solution and warm if crystals are present; do not administer undissolved.

Common:

• Headache
• Nausea, vomiting
• Dry mouth or thirst
• Diuresis and electrolyte imbalance
• Injection site phlebitis

Serious:

• Pulmonary edema
• Congestive heart failure exacerbation
• Acute kidney injury
• Hyponatremia or hypernatremia
• Seizures (from hyponatremia or cerebral dehydration)
• Rebound increased intracranial pressure

Timing: Effects such as diuresis occur within 1–3 hours; adverse effects vary with dose, rate, and patient condition.

• Nephrotoxic Agents (e.g., aminoglycosides, amphotericin B): Increased risk of renal injury
• Diuretics (loop or thiazide): Additive diuretic effect; higher risk of hypovolemia and electrolyte loss
• Digoxin: Hypokalemia from mannitol use can increase digoxin toxicity
• Lithium: May increase lithium clearance and reduce its efficacy

Enzyme Pathways: Mannitol does not interact with CYP450 enzymes.

• Neurology/Critical Care: Mannitol remains a standard for lowering ICP, though hypertonic saline is often preferred in certain settings.
• Nephrology: Routine use to prevent AKI or contrast-induced nephropathy is not supported by current evidence.
• FDA/EMA: No recent major safety labeling changes. Focus remains on avoiding overuse and monitoring serum osmolality.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Crystallization: Solutions >15% may crystallize; warm to 37°C and shake until dissolved
• Light Protection: Not required
• Handling Instructions:
• Use in-line filter for IV infusion
• Do not use if crystals persist after warming
• Do not mix with blood transfusions in the same IV line
• Do not freeze