Mannitol is a carbohydrate that accumulates primarily in the extracellular space. When administered intravenously, it increases the osmotic pressure of extracellular fluid, causing water to move from the intracellular compartment into interstitial fluid and plasma. This results in a reduction of intracranial pressure, a decrease in intraocular pressure, and minimization of edema. Mannitol passes from the blood into the renal tubules, where it undergoes glomerular filtration. The site of action is the proximal tubule and the loop of Henle. The drug is essentially not reabsorbed into the blood; it increases the osmotic pressure of the glomerular filtrate, passes into the distal portion of the nephron, and is excreted in the final urine. The drug increases circulating fluid volume and prevents renal failure. Its mechanism of action also involves the release of prostaglandin E2 and prostacyclin, increased clearance of myoglobin, phosphates, and uric acid. Mannitol also acts as a free radical scavenger, reducing oxidative stress. Mannitol presumably increases osmotic pressure in the respiratory epithelium, causing water to move into the extracellular space, thereby reducing the viscosity of airway secretions in the lungs and facilitating their clearance.
Peak mannitol concentration following inhalation occurs within 1.5 ± 0.5 hours.
Mannitol is distributed almost exclusively in the extracellular space.
Mannitol is excreted unchanged primarily by the kidneys. Only 10% of the dose may be reabsorbed from the renal tubules into the blood. The elimination half-life is approximately 4–5 hours and may be prolonged in patients with renal impairment to up to 36 hours.
⚠️ Warnings
If signs of hypersensitivity occur, administration must be discontinued immediately.
Some patients have experienced symptoms of central nervous system toxicity (drowsiness, disorientation, coma). This applies particularly to patients with severe renal impairment. Fatalities have also been reported. High mannitol concentrations may cause the drug to cross the blood-brain barrier and increase the risk of acid-base imbalance in cerebrospinal fluid. In patients with a compromised blood-brain barrier, there is a greater likelihood of increased cerebral edema. In this patient group in particular, the possibility of a rebound increase in intracranial pressure within several hours after administration should be considered.
Large doses of mannitol may initiate reversible renal failure. In extreme cases, large doses carry the risk of permanent or even end-stage renal failure. Particular caution is required in patients with pre-existing renal impairment and those receiving other nephrotoxic drugs. Urine output should be carefully monitored for any decrease.
Initiation of mannitol therapy in patients with shock and renal impairment requires prior correction of fluid volume and electrolyte levels.
Cardiovascular function should be assessed before starting mannitol administration, as large doses and rapid infusion may cause the development or worsening of congestive heart failure. Respiratory function and central venous pressure should also be monitored.
Mannitol may cause acid-base disturbances and electrolyte imbalances (hypernatremia/hyponatremia, excessive dehydration, hyperkalemia/hypokalemia).
Mannitol should not be administered concurrently with blood (risk of pseudoagglutination).
Increased risk of enhanced cerebral blood flow and postoperative bleeding exists in patients following neurosurgical procedures.
When using the inhaled formulation, attention should be paid to signs of bronchospasm and the benefit-risk ratio should be carefully evaluated. Inhaled mannitol may cause severe hemoptysis, which warrants discontinuation of therapy. The prescribing physician should be informed of any persistent cough during treatment with inhaled mannitol.
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