ICP lowering agents and rebound phenomenon

Q: Which of the following can have the highest "rebound effect" during the management of high Intracranial Pressure(ICP)? - select one

A) Mannitol 

B) Furosemide

C) Glycerol 

D) Urea

Answer: C

All of the above agents have been used in the management of high ICP; however, mannitol remains the leading agent and is considered the standard.

'Rebound phenomenon' may occur after repeated administration of mannitol and glycerol, when these agents reenter the brain through a damaged blood-brain barrier and reverse the osmotic gradient. This requires continued monitoring of serum sodium, serum osmolality, and renal function even after these agents are discontinued. Serum sodium >150 mEq, serum osmolality >320 mOsm, significant hypotension, or evidence of evolving acute tubular necrosis (ATN) should lead a clinician to consider the stoppage of these osmotic diuretics.

Glycerol and urea have been tried in the past with the hope that they work more quickly than mannitol, but have fallen out of favor as they can have a significant rebound effect, particularly with glycerol. Additionally, glycerol is less effective in ICP control.

Furosemide, administered intravenously at 0.5 to 1.0 mg/kg, has been combined with mannitol to enhance its effect; however, dehydration and hypokalemia may limit its use.

#neuro-critical-care

References: 

1. Chesnut RM, Marshall LF. Management of head injury. Treatment of abnormal intracranial pressure. Neurosurg Clin N Am 1991; 2:267.

2. Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg 1992; 77:584.

3. Pollay M, Fullenwider C, Roberts PA, Stevens FA. Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure. J Neurosurg 1983; 59:945.

4. Otvos B, Kshettry VR, Benzel EC. The history of urea as a hyperosmolar agent to decrease brain swelling. Neurosurg Focus. 2014 Apr;36(4):E3. doi: 10.3171/2014.1.FOCUS13558. PMID: 24684336.

5. Node Y, Nakazawa S. Clinical study of mannitol and glycerol on raised intracranial pressure and on their rebound phenomenon. Adv Neurol 1990; 52:359.