Mannitol Half-Life
The elimination half-life of mannitol is 0.5 to 2.5 hours in patients with normal renal function, but is dramatically prolonged to approximately 36 hours in patients with renal impairment including acute renal failure and end-stage renal disease. 1, 2
Normal Renal Function
- In patients with normal renal function, mannitol has a plasma distribution half-life of 0.16 hours (approximately 10 minutes) and an elimination half-life ranging from 0.5 to 2.5 hours 1
- The total clearance in normal subjects is 87 to 109 mL/minute, with approximately 80% of a 100 g dose appearing in the urine within 3 hours 1
- Mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption and no tubular secretion 1
Renal Impairment
- In patients with renal impairment, including acute renal failure and end-stage renal failure, the elimination half-life is markedly prolonged to approximately 36 hours 1, 2
- This represents a 14- to 72-fold increase compared to normal renal function, creating substantial risk for drug accumulation and toxicity 1, 2
Dialysis Considerations
- Hemodialysis significantly reduces the elimination half-life to approximately 6 hours, making it the ideal treatment for mannitol intoxication 1, 2
- Peritoneal dialysis is less effective, reducing the half-life to only 21 hours 1, 2
- The dramatic difference in clearance between hemodialysis and peritoneal dialysis makes hemodialysis the preferred modality for mannitol removal in cases of toxicity 2
Critical Clinical Implications
- Serum osmolality must be monitored frequently and maintained below 320 mOsm to avoid renal failure, particularly in patients with any degree of renal impairment 3
- Mannitol should be administered with extreme caution and is specifically contraindicated in oligoanuric patients 4
- The prolonged half-life in renal impairment creates risk for severe complications including hyponatremia, hyperosmolality (osmolar gap >70 mosm/kg), fluid overload, and CNS involvement 2, 5
- Mannitol-induced acute renal failure has been documented at infusion rates of approximately 0.25 g/kg/h, with toxicity typically manifesting 48 hours after infusion begins 5