From the Guidelines
Mannitol can lead to hypernatremia as a result of its osmotic diuretic effect, which may cause an increase in serum sodium levels, particularly with overzealous use or in patients with renal impairment. This is because mannitol draws water from tissues and cells into the bloodstream, initially diluting the blood, but as the kidneys excrete the excess water more rapidly than sodium, the serum sodium concentration rises 1. The administration of intravenous mannitol, as recommended in a bolus dose of 0.5-1g/kg, may be repeated once or twice as needed, provided serum osmolality has not exceeded 320 mosm/L, but it requires careful monitoring of serum sodium levels to avoid hypernatremia 1. Key considerations when using mannitol include:
- Monitoring serum osmolality to avoid exceeding 320 mosm/L
- Risk of volume overload in patients with renal impairment, which may necessitate dialysis
- Potential for hyperosmolarity or hypernatremia with overzealous use
- Importance of close monitoring of serum sodium levels, especially in patients with pre-existing electrolyte abnormalities or renal dysfunction.
From the FDA Drug Label
With continued administration of mannitol, loss of water in excess of electrolytes can cause hypernatremia The shift of sodium-free intracellular fluid into the extracellular compartment following mannitol infusion may lower serum sodium concentration and aggravate pre-existing hyponatremia
Mannitol may have a dual effect on serum sodium levels.
- It can cause hypernatremia due to the loss of water in excess of electrolytes.
- It can also lower serum sodium concentration by shifting sodium-free intracellular fluid into the extracellular compartment, potentially aggravating pre-existing hyponatremia 2.
From the Research
Effect of Mannitol on Serum Sodium Levels
- Mannitol can cause a decrease in serum sodium levels, leading to hyponatremia, as seen in a case study where a patient undergoing transurethral prostatic resection developed severe hyponatremia due to the absorption of mannitol irrigation solution 3.
- A study on brain injury patients found that hyponatremia was observed in 12.2% of subjects on the first day of mannitol administration and in 9-24% throughout the 7-day administration period 4.
- Another study found that high-dose mannitol administration resulted in a significant decrease in serum sodium levels, with the decrease being greater in patients receiving the larger dose of mannitol 5.
- In contrast, a study on rats found that mannitol prevented the development of acute hyponatremia by reducing the rate of excretion of Na+ and increasing the excretion of electrolyte-free water 6.
Mechanism of Action
- The exact mechanism of the effect of mannitol on serum sodium levels is unclear, but it is thought to involve the osmotic diuretic properties of mannitol, which can lead to an increase in urine output and a decrease in serum sodium levels 4, 5.
- Mannitol can also cause an increase in serum osmolality, which can lead to a shift of water from the intracellular to the extracellular space, resulting in a decrease in serum sodium levels 3, 5.
Clinical Implications
- The use of mannitol can lead to significant alterations in serum electrolyte levels, including sodium, potassium, and osmolality, and careful monitoring of these levels is essential when administering repeated doses of mannitol 4, 5.
- The development of hyponatremia or hypernatremia can have significant clinical implications, and the use of mannitol should be carefully considered in patients with risk factors for electrolyte imbalances 3, 4, 5.