Mannitol

Mechanism

Pharmacological Group

Osmotic diuretic derived from sugar alcohols.

Mechanism of Action

Mannitol is a pharmacologically inert solute. After rapid intravenous administration, it is distributed only in the extracellular space and does not cross the blood-brain barrier (unless it is severely damaged) or penetrate cells. This generates a transcellular osmotic gradient that draws free water from the intracellular compartment into the extracellular vascular space. At the renal level, it is freely filtered by the glomerulus but is completely incapable of being reabsorbed in the nephron. Its physical presence in the lumen of the Proximal Convoluted Tubule and the Descending Branch of Henle retains water by osmotic force, limiting its reabsorption:

This promotes a massive free water diuresis, accompanied by a minor secondary increase in urinary sodium due to solvent drag.

Pharmacokinetics

Key Pharmacokinetics

• Administration: Exclusively by intravenous (IV) route through catheter or large-caliber peripheral vein. Oral ingestion causes severe non-resorptive osmotic diarrhea.
• Distribution: Does not cross intact cellular barriers. It does not undergo significant metabolism in the body.
• Excretion: Rapid elimination by glomerular filtration in its unchanged form (90% in the first 24 hours).
• Half-life: 1 to 2 hours (very prolonged in acute renal failure).

Danger of Acute Lung Edema and Transient Hypervolemia

By massively drawing intracellular water into the extracellular compartment, mannitol causes rapid and massive intravascular volume expansion shortly after infusion. In patients with depressed cardiac reserve or underlying congestive heart failure, this sudden increase in preload can immediately precipitate acute pulmonary edema, decompensated heart failure, and lethal systemic congestion. Likewise, if urine is not evacuated (e.g. anuria due to ATN), the accumulation of mannitol in the blood constantly attracts water, inducing severe dilutional hyponatremia and extreme hypervolemia.

Indicators and dose

Clinical Indications

• Reduction of elevated intracranial pressure (ICP): In the presence of acute cerebral edema secondary to head trauma, tumors or strokes.
• Reduction of acutely elevated intraocular pressure (IOP): In acute attacks of angle-closure glaucoma when other measures do not work.
• Prevention of acute tubular necrosis (historical): Used to force diuresis and sweep intratubular debris in cases of severe rhabdomyolysis (myoglobinuria), although its current clinical benefit is controversial compared to vigorous hydration alone.

Dosage and Settings

• Intracranial Pressure: Infusion of 0.25 g to 1 g/kg of body weight of a 20% solution (Osmofundin) over a period of 30 to 60 minutes. Avoid continuous fixed use to prevent accumulation of mannitol in the brain across the damaged blood-brain barrier (which would reverse the gradient and induce rebound edema).
• Test dose: In severe oliguria, infuse 0.2 g/kg over 3-5 minutes to demonstrate a minimal diuretic response (>40 mL/h over the next 2 hours) before initiating formal therapy.

Security

Contraindications

• Absolute: Anuria established by severe renal disease refractory to test doses of mannitol; severe decompensated congestive heart failure; active pulmonary congestion or edema; active non-surgical intracranial hemorrhage (mannitol can shrink the brain parenchyma, expand the subdural space and worsen bleeding); previous severe dehydration.

Adverse Effects (ADR)

• Very common: Intense headache (due to traction of meningeal vessels when the brain shrinks), nausea, vomiting, chills due to the infusion.
• Serious: Acute renal failure due to tubular osmotic vacuolization (osmotic nephrosis, typically at high cumulative doses), initial dilutional hyponatremia, late dehydrating hypernatremia (due to exclusive loss of free water).

Interactions

Toxic synergy with powerful diuretics. It can disrupt lithium clearance by forcing massive filtration.

Pregnancy and Breastfeeding

Category C. It partially crosses the placenta and can induce volume and electrolyte imbalances in the fetus. Reserve exclusively for maternal life-threatening emergencies.