What are the potential side effects of intravenous (IV) mannitol, especially in patients with pre-existing renal impairment or heart failure?

Side Effects of Intravenous Mannitol

Intravenous mannitol carries significant risks of renal failure, fluid and electrolyte imbalances, and cardiovascular complications, particularly in patients with pre-existing renal impairment, heart failure, diabetes, or hypertension. 1

Critical Contraindications

Mannitol is absolutely contraindicated in the following conditions 1:

• Well-established anuria due to severe renal disease
• Severe pulmonary congestion or frank pulmonary edema
• Active intracranial bleeding (except during craniotomy)
• Severe dehydration
• Progressive heart failure or pulmonary congestion after mannitol initiation

Renal Complications

Acute renal failure is the most serious side effect of mannitol, particularly with high-dose or prolonged administration. 1

High-Risk Populations for Renal Toxicity

Patients at increased risk include those with 2, 1, 3:

• Pre-existing renal disease
• Diabetes mellitus
• Hypertension
• Coronary artery disease
• Congestive heart failure
• High APACHE II scores on admission

Mechanism and Prevention

• Mannitol-induced acute renal failure (MI-ARI) is characteristically anuric and occurs primarily after high doses (>200 g/day or cumulative dose >400 g in 48 hours). 4
• Low-dose mannitol acts as a renal vasodilator, while high-dose mannitol causes renal vasoconstriction. 4
• Serum osmolality must be monitored frequently, and mannitol should be discontinued when osmolality exceeds 320 mOsm/L to prevent renal failure. 5, 2, 6, 1
• Concomitant use of nephrotoxic drugs or other diuretics significantly increases renal failure risk and should be avoided. 2, 6, 1

Clinical Presentation of Mannitol-Induced Renal Failure

Patients may develop 7, 8:

• Nausea and vomiting
• Progressive lethargy
• Generalized edema
• Congestive heart failure
• Severe dilutional hyponatremia with hyperosmolality

Management of Mannitol-Induced Renal Failure

Hemodialysis should be performed for rapid reversal of mannitol-induced acute renal failure. 4 Patients not treated with hemodialysis experience increased morbidity and significantly prolonged hospital courses. 4 Extracorporeal ultrafiltration (ECUM) and hemodialysis have been used successfully. 7

Fluid and Electrolyte Imbalances

Mannitol causes profound osmotic diuresis leading to multiple electrolyte disturbances. 1

Specific Electrolyte Complications

• Hypernatremia and hyponatremia (dilutional hyponatremia with hyperosmolality is particularly dangerous) 1, 7
• Hypokalemia 9
• Hypomagnesemia 9
• Acidosis 1
• Dehydration 1

Volume Status Changes

• Mannitol may obscure and intensify inadequate hydration or hypovolemia. 1
• A Foley catheter must be inserted before administration due to profound osmotic diuresis. 5
• Monitor for hypovolemia and provide adequate volume replacement with crystalloids or plasma expanders. 5

Cardiovascular Complications

Mannitol accumulation may intensify existing or latent congestive heart failure. 9, 1

Common cardiovascular side effects include 1:

• Pulmonary congestion (most common adverse reaction)
• Edema
• Hypotension
• Tachycardia
• Angina-like chest pains
• Congestive heart failure exacerbation

Monitoring of cardiovascular status is essential, and mannitol should be discontinued if cardiac status worsens. 1

Central Nervous System Toxicity

Paradoxical CNS effects can occur 1:

• Mannitol may increase cerebral blood flow and the risk of postoperative bleeding in neurosurgical patients. 1
• May worsen intracranial hypertension in children who develop generalized cerebral hyperemia during the first 24-48 hours post-injury. 1
• Headache 1
• Blurred vision 1
• Convulsions 1
• Dizziness 1

Other Common Side Effects

Additional adverse reactions include 1:

• Dryness of mouth and thirst
• Marked diuresis
• Urinary retention
• Nausea and vomiting
• Rhinitis
• Arm pain
• Skin necrosis
• Thrombophlebitis
• Chills
• Urticaria
• Fever

Special Populations Requiring Caution

Elderly Patients

Mannitol is substantially excreted by the kidney, and elderly patients with impaired renal function face greater risk of adverse reactions. 1 Evaluate renal, cardiac, and pulmonary status and correct fluid and electrolyte imbalances prior to administration. 1

Pregnant Women

Mannitol crosses the placenta and may cause fluid shifts potentially resulting in adverse fetal effects. 1 It should only be given to pregnant women if clearly needed. 1

Critical Monitoring Requirements

Discontinue mannitol immediately if renal, cardiac, or pulmonary status worsens, or if CNS toxicity develops. 1

Essential monitoring includes 5, 2, 6, 1:

• Serum osmolality (discontinue if >320 mOsm/L)
• Electrolyte levels (sodium, potassium, magnesium)
• Renal function (creatinine, BUN)
• Cardiovascular status
• Urine output (via Foley catheter)
• Volume status

Important Clinical Caveats

• Hypertonic saline is preferable over mannitol when hypovolemia, hypotension, or renal dysfunction is present. 5, 6
• Do not add mannitol to whole blood for transfusion. 1
• Use a filter in the administration set when infusing 25% mannitol. 6
• Rebound intracranial hypertension can occur with prolonged use or rapid discontinuation. 5
• Mannitol is a temporizing measure only and does not improve long-term outcomes in ischemic brain swelling. 5