What is the mechanism of action, dose, route, considerations, contraindications, adverse effects, and nursing considerations for Mannitol (mannitol) in a patient with cerebral edema (cerebral edema) post-trauma (post-traumatic injury)?

From the Guidelines

Mannitol is recommended for the treatment of cerebral edema following trauma, with a dose of 0.25-1 g/kg administered intravenously over 30-60 minutes, and maintenance doses of 0.25-0.5 g/kg every 4-6 hours as needed, as it has been shown to reduce intracranial pressure and improve cerebral oxygenation 1. The mechanism of action of mannitol involves increasing plasma osmolality, drawing fluid from brain tissue into the bloodstream, thereby reducing intracranial pressure. Some key points to consider when using mannitol include:

• The typical dose for adults is 0.25-1 g/kg administered intravenously over 30-60 minutes, with maintenance doses of 0.25-0.5 g/kg every 4-6 hours as needed, with a recommended dose of 250 mOsm in infusion of 15–20 minutes to treat threatened intracranial hypertension or signs of brain herniation 1.
• Mannitol should be administered through a filter using an infusion pump to ensure accurate delivery.
• Contraindications include severe dehydration, active intracranial bleeding, severe renal impairment (anuria), and severe heart failure.
• Adverse effects include fluid and electrolyte imbalances (particularly hyponatremia and hypokalemia), dehydration, hypotension, tachycardia, headache, nausea, vomiting, and renal failure.
• Nursing considerations include monitoring vital signs, neurological status, intake and output, serum electrolytes, and renal function.
• Ensure adequate hydration before administration, watch for signs of fluid overload or dehydration, and inspect the solution for crystals (warming may be needed to dissolve them).
• Assess for rebound cerebral edema when discontinuing therapy and monitor for signs of increased intracranial pressure.
• Mannitol should be used cautiously in patients with heart or kidney disease and should not be mixed with blood products or administered through the same line. It is also important to note that mannitol has comparable efficacy to hypertonic saline in treating intracranial hypertension, but side effects such as osmotic diuresis and hypernatremia should be considered 1. Some other key considerations include:
• Monitoring fluid, sodium, and chloride balances is necessary when using mannitol or hypertonic saline.
• The use of hypertonic saline solutions has been shown to reduce ICP in a variety of conditions, even in cases refractory to treatment with hyperventilation and mannitol 1.
• Osmotherapy reduces the intracranial pressure (ICP) with a maximum effect observed after 10–15 minutes and for a duration of 2–4 hours, in order to restore cerebral blood flow (CBF) 1.

From the FDA Drug Label

MANNITOL injection, for intravenous use Initial U. S. Approval: 1964 INDICATIONS AND USAGE Mannitol Injection is indicated for the following purposes in adults and pediatric patients. Therapeutic Use Reduction of intracranial pressure and brain mass. ( 1) Reduction of high intraocular pressure. ( 1) Diagnostic Use Measurement of glomerular filtration rate. ( 1) DOSAGE AND ADMINISTRATION Administration Instructions ( 2-2. 1): For intravenous use only. Do not add mannitol in whole blood for transfusion. Recommended Dosage ( 2-2.2): The dosage, concentration and rate of administration depend on the age, weight and condition of the patient. Reduction of Intracranial Pressure and Brain Mass: Adults: 0. 25 to 2 g/kg body weight as a 15% to 25% solution administered over a period of 30 to 60 minutes Pediatric patients: 1 to 2 g/kg body weight or 30 to 60 g/m2 body surface area over a period of 30 to 60 minutes Small or debilitated patients: 500 mg/kg CONTRAINDICATIONS Well established anuria due to severe renal disease. ( 4) Severe pulmonary congestion or frank pulmonary edema. ( 4) Active intracranial bleeding except during craniotomy ( 4) Severe dehydration. ( 4) Progressive heart failure or pulmonary congestion after institution of mannitol therapy. ( 4) Do not administer to patients with a known hypersensitivity to mannitol ( 4) WARNINGS AND PRECAUTIONS Renal Complications Including Renal Failure: Risk factors include pre-existing renal disease, conditions that put patients at risk for renal failure and concomitant use of nephrotoxic drugs or other diuretics. Avoid concomitant administration of nephrotoxic drugs or other diuretics with mannitol. ( 5-5.1,8-8. 6) Fluid and Electrolyte Imbalances: Mannitol administration may obscure and intensify inadequate hydration or hypovolemia. Excessive loss of water and electrolytes may lead to serious imbalances, e.g., hypernatremia, hyponatremia. Accumulation of mannitol may intensify existing or latent congestive heart failure. Monitoring of cardiovascular status and electrolyte levels is recommended. ( 5-5. 2) Central Nervous System (CNS) Toxicity: Mannitol may increase cerebral blood flow and the risk of postoperative bleeding in neurosurgical patients. It may also worsen intracranial hypertension in children who develop a generalized cerebral hyperemia during the first 24 to 48 hours post injury. ( 5-5. 3) Monitoring: Discontinue mannitol if renal, cardiac or pulmonary status worsens, or CNS toxicity develops. ( 5-5. 4) ADVERSE REACTIONS Most common adverse reactions are pulmonary congestion, fluid and electrolyte imbalance, acidosis, electrolyte loss, dryness of mouth, thirst, marked diuresis, urinary retention, edema, headache, blurred vision, convulsions, nausea, vomiting, rhinitis, arm pain, skin necrosis, thrombophlebitis, chills, dizziness, urticaria, dehydration, hypotension, tachycardia, fever and angina-like chest pains. ( 6)

The mechanism of action of mannitol is not explicitly stated in the provided drug label. However, the dose for reduction of intracranial pressure and brain mass in adults is 0.25 to 2 g/kg body weight as a 15% to 25% solution administered over a period of 30 to 60 minutes. The route of administration is intravenous use only. Considerations include:

• Monitoring of cardiovascular status and electrolyte levels
• Avoiding concomitant administration of nephrotoxic drugs or other diuretics
• Discontinuing mannitol if renal, cardiac or pulmonary status worsens, or CNS toxicity develops Contraindications include:
• Well established anuria due to severe renal disease
• Severe pulmonary congestion or frank pulmonary edema
• Active intracranial bleeding except during craniotomy
• Severe dehydration
• Progressive heart failure or pulmonary congestion after institution of mannitol therapy
• Known hypersensitivity to mannitol Adverse effects include:
• Pulmonary congestion
• Fluid and electrolyte imbalance
• Acidosis
• Electrolyte loss
• Dryness of mouth
• Thirst
• Marked diuresis
• Urinary retention
• Edema
• Headache
• Blurred vision
• Convulsions
• Nausea
• Vomiting
• Rhinitis
• Arm pain
• Skin necrosis
• Thrombophlebitis
• Chills
• Dizziness
• Urticaria
• Dehydration
• Hypotension
• Tachycardia
• Fever
• Angina-like chest pains Nursing considerations include:
• Monitoring patient's renal, cardiac, and pulmonary status
• Monitoring patient's electrolyte levels
• Assessing patient for signs of CNS toxicity
• Ensuring patient is well-hydrated before administration
• Avoiding extravasation during administration 2

From the Research

Mechanism of Action

• Mannitol acts by creating an osmotic gradient that draws cerebral edema fluid from brain tissue into the circulation, thereby reducing intracranial pressure 3, 4
• Another mechanism may be involved, such as a reduction in brain water, as a single bolus of 1 g/kg of 20% mannitol does not acutely lower cerebral blood volume 3

Dose and Route

• A dose of 1.0 g/kg of 20% mannitol is commonly used to reduce intracranial pressure in patients with head injury 3
• Multiple doses of mannitol can be administered, with studies showing that four to eight doses of 20% mannitol (0.4 g/kg) can be given without aggravating total hemispheric swelling or global water content following induction of vasogenic edema 5
• The route of administration is typically intravenous, with central intravenous administration preferred for hypertonic saline, but peripheral intravenous administration also safe provided measures are undertaken to detect and prevent phlebitis and extravasation 6

Considerations

• Mannitol can cause renal toxicity and fluid accumulation in the brain parenchyma with consequent worsening of cerebral edema, especially with multiple administrations 7
• Hypertonic saline solutions, such as 23.4% sodium chloride, can be used as an adjunct to mannitol or as an alternative, with a longer duration of effect and no significant differences in reductions in intracranial pressure compared to mannitol 7
• Monitoring of serum sodium and chloride concentrations is necessary to ensure safe use of hypertonic saline 6

Contraindications

• No specific contraindications are mentioned in the studies, but caution should be exercised in patients with renal impairment or those at risk of fluid accumulation in the brain parenchyma 7, 5

Adverse Effects

• Adverse events with use of hypertonic saline are often mild and non-clinically significant if appropriate monitoring of serum sodium and chloride concentrations is performed 6
• Mannitol can cause renal toxicity and fluid accumulation in the brain parenchyma with consequent worsening of cerebral edema 7

Nursing Considerations

• Nurses should be familiar with management guidelines and the use of hyperosmolar solutions, including mannitol and hypertonic saline, in the treatment of pediatric traumatic brain injury 4
• Proper protocols, education, and institutional safeguards should be in place to ensure safe use of hypertonic saline, including monitoring of serum sodium and chloride concentrations and detection and prevention of phlebitis and extravasation 6