Mannitol is a carbohydrate that accumulates primarily in the extracellular space. After intravenous administration, the drug increases the osmotic pressure of extracellular fluid, leading to the movement of water from inside cells into the interstitial fluid and plasma. This results in reduced intracranial pressure, reduced 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 of the nephron. The drug is practically not reabsorbed into the blood; it increases the osmotic pressure of the glomerular filtrate, passes into the distal part of the nephron, and is excreted as final urine. The drug increases the volume of circulating fluids 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 probably increases osmotic pressure in the respiratory tract epithelium, causing water to move into the extracellular space, thereby reducing the viscosity of airway secretions in the lungs and facilitating their clearance.
Peak plasma concentration of mannitol after 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 tubule into the blood. The elimination half-life is approximately 4–5 hours and may be prolonged in patients with renal impairment up to 36 hours.
⚠️ Warnings
In the event of hypersensitivity symptoms, drug administration must be discontinued immediately.
Some patients experienced symptoms of central nervous system toxicity (drowsiness, disorientation, coma). This particularly applies to patients with severe renal impairment. Fatal outcomes have also been reported. High concentrations of mannitol may cause the drug to cross the blood-brain barrier and increase the risk of cerebrospinal fluid acid-base imbalance. In patients with a compromised blood-brain barrier, there is a greater likelihood of increased cerebral edema. In this patient group especially, the possibility of rebound increase in intracranial pressure within several hours after drug administration should be considered.
Large doses of mannitol may initiate the development of reversible renal failure. In extreme cases, large doses of mannitol 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 initiating 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 imbalance and electrolyte disturbances (hypernatremia/hyponatremia, excessive dehydration, hyperkalemia/hypokalemia).
Mannitol must not be administered simultaneously with blood (risk of pseudoagglutination).
Increased risk of enhanced cerebral blood flow and postoperative hemorrhage exists in patients who have undergone neurosurgical procedures.
When using the inhaled form, attention should be paid to signs of bronchospasm and the benefit-risk ratio should be evaluated. Inhaled mannitol may cause severe hemoptysis, which indicates the need to discontinue the drug. The treating physician should be informed of any persistent cough during treatment with inhaled mannitol.
