What is the role of mannitol in the treatment of diabetic ketoacidosis (DKA) in children?

From the Guidelines

Mannitol is not recommended for use in children with diabetic ketoacidosis (DKA). In pediatric DKA management, the focus should be on careful fluid resuscitation with isotonic fluids (typically normal saline), insulin therapy, and electrolyte management. If cerebral edema is suspected—a rare but serious complication of pediatric DKA—the preferred treatment is intravenous hypertonic saline (3% NaCl) at 5-10 mL/kg over 30 minutes rather than mannitol. While mannitol (0.5-1 g/kg) has historically been used for DKA-related cerebral edema, hypertonic saline is now generally preferred as it provides more consistent osmotic effects without the potential rebound phenomena associated with mannitol. Additionally, mannitol can worsen dehydration and electrolyte abnormalities already present in DKA. The management of pediatric DKA should always include close monitoring of neurological status, careful fluid administration to avoid rapid changes in serum osmolality, gradual correction of hyperglycemia, and addressing the underlying cause of the DKA episode.

Key Considerations

• The most recent and highest quality study 1 emphasizes the importance of individualization of treatment based on a careful clinical and laboratory assessment.
• The use of mannitol in DKA is not supported by recent evidence, and its potential to worsen dehydration and electrolyte abnormalities is a concern.
• Hypertonic saline is preferred over mannitol for the treatment of cerebral edema in pediatric DKA due to its more consistent osmotic effects and lower risk of rebound phenomena.
• Close monitoring of neurological status, careful fluid administration, and gradual correction of hyperglycemia are crucial in the management of pediatric DKA.

Treatment Approach

• Initiate fluid replacement therapy with isotonic fluids (typically normal saline) based on recommendations in position statements 1.
• Use intravenous insulin therapy according to recommendations in position statements 1.
• Monitor serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH every 2-4 hours during therapy for DKA or HHS 1.
• Consider the use of hypertonic saline (3% NaCl) at 5-10 mL/kg over 30 minutes for the treatment of cerebral edema in pediatric DKA.

From the FDA Drug Label

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)

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.

The FDA drug label does not answer the question about the use of mannitol in a child with DKA.

From the Research

DKA in Children and Mannitol Treatment

• Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus that can occur in children, with cerebral edema being a devastating complication [(2,3,4,5,6)].
• Cerebral edema in DKA can be treated with mannitol, which has been traditionally used, but the use of 3% hypertonic saline has become an accepted alternative [(2,4,5)].
• A study found that the use of 3% hypertonic saline alone was associated with a higher mortality than mannitol alone in patients treated for cerebral edema 2.
• Mannitol has been shown to be effective in reversing cerebral edema in DKA, with prompt institution of treatment being beneficial 5.
• The management of DKA in children requires careful replacement of fluid and electrolyte deficits, intravenous administration of insulin, and close monitoring of clinical and biochemical parameters [(3,4,6)].

Key Findings

• Cerebral edema occurs in 0.5-0.9% of all episodes of DKA and is a major cause of death in childhood DKA 6.
• Treatment of cerebral edema should be prompt and immediate, with mannitol being a commonly used treatment [(3,4,5)].
• The use of hypertonic saline has replaced mannitol as the most commonly used agent at many institutions for treatment of cerebral edema in DKA, but its use has been associated with a higher mortality 2.
• Successful DKA management in children depends upon swift diagnosis, meticulous monitoring of clinical and biochemical parameters with prompt intervention 6.