Osmotic Diuretics: Definition and Clinical Applications
Osmotic diuretics are medications that work by increasing the osmotic pressure of plasma and extracellular fluid, drawing water from tissues (including brain and eye) into the intravascular space, where it is then excreted by the kidneys. 1
Mechanism of Action
Osmotic diuretics function through two primary mechanisms:
Osmotic gradient creation: When administered intravenously, these agents (particularly mannitol) remain largely confined to the extracellular space due to their relatively small molecular size, creating an osmotic gradient that pulls intracellular water into the extracellular and vascular compartments 1
Renal effects: These agents are freely filtered by the glomeruli and hinder tubular reabsorption of water while enhancing excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate 1
Primary Clinical Indications
Reduction of Intracranial Pressure
Mannitol is the first-line osmotic agent for managing elevated intracranial pressure in conditions such as traumatic brain injury, intracerebral hemorrhage, and cerebral edema, with demonstrated improvement in cerebral oxygenation compared to other therapies 2, 3
The American Heart Association recommends mannitol at 0.25 to 0.5 g/kg IV administered over 20 minutes, which can be repeated every 6 hours as needed, with a maximum daily dose of 2 g/kg 2
Mannitol should be administered when there are obvious neurological signs of increased ICP, such as pupillary abnormalities, declining level of consciousness (GCS ≤8), or acute neurological deterioration not attributable to systemic causes 2, 3
Reduction of Intraocular Pressure
Osmotic diuretics are indicated for acute glaucoma to rapidly reduce intraocular pressure 1, 4
The FDA-approved dosing for intraocular pressure reduction is 0.25 to 2 g/kg body weight as a 15% to 25% solution administered over 30 to 60 minutes 1
Diagnostic Use
- Mannitol can be used for measurement of glomerular filtration rate (GFR), typically using 20 g diluted to a 7.2% solution infused at 20 mL per minute 1
Pharmacokinetics and Clinical Considerations
Distribution and Elimination
Mannitol distributes to the extracellular space within 20 to 40 minutes after intravenous administration, with a volume of distribution of approximately 17 L in adults 1
In patients with normal renal function, the elimination half-life is 0.5 to 2.5 hours, with approximately 80% of the dose appearing in urine within 3 hours 1
In renal impairment, the elimination half-life is markedly prolonged to approximately 36 hours, creating significant risk of accumulation 1, 5
Critical Monitoring Parameters
Serum osmolality must be monitored to ensure it remains below 320 mOsm/L, as exceeding this threshold is associated with increased risk of renal failure and other complications 2, 3
Cerebral perfusion pressure should be maintained between 60-70 mmHg during mannitol administration, as this range optimizes outcomes while avoiding complications 2, 3
Electrolytes should be checked every 6 hours during active mannitol therapy, as osmotic diuresis can cause significant fluid and electrolyte imbalances including hypernatremia, hyponatremia, and hypovolemia 2
Absolute Contraindications
The FDA label specifies the following contraindications 1:
Well-established anuria due to severe renal disease - mannitol accumulation in renal failure can cause acute renal failure, confusion, lethargy, and potentially coma 6, 4
Severe pulmonary congestion or frank pulmonary edema 1
Active intracranial bleeding except during craniotomy 1
Severe dehydration 1
Progressive heart failure or pulmonary congestion after institution of mannitol therapy 1
Known hypersensitivity to mannitol 1
Alternative Osmotic Agents
Hypertonic saline (3%) is an effective alternative to mannitol, with comparable efficacy at equiosmotic doses (approximately 250 mOsm) 2, 3
Hypertonic saline is the superior choice in settings of hypotension or hypovolemia, as it has minimal diuretic effect and can increase blood pressure, whereas mannitol causes potent osmotic diuresis that can worsen hypotension 2, 3
Glycerol is another osmotic agent that can be used, though it is not recommended as a first-line agent and may affect glucose metabolism 5, 7
Critical Adverse Effects and Precautions
Renal failure: Risk factors include pre-existing renal disease, concomitant nephrotoxic drugs, and repeated high-dose administration 1, 8, 6
Rebound intracranial hypertension: Can occur with prolonged use or rapid discontinuation, as mannitol accumulates in CSF and reverses the osmotic gradient 2, 5
Fluid and electrolyte imbalances: Excessive loss of water and electrolytes may lead to serious imbalances, and accumulation may intensify congestive heart failure 1, 8
Avoid concomitant administration of nephrotoxic drugs or other diuretics with mannitol to minimize renal complications 1