What is the management and prevention of Acute Kidney Injury (AKI) induced by mannitol?

Management and Prevention of Mannitol-Induced Acute Kidney Injury

Immediately discontinue mannitol and initiate hemodialysis or ultrafiltration if oliguria develops or serum osmolal gap exceeds 55 mOsm/kg, as mannitol-induced AKI is reversible with prompt intervention but can progress to irreversible renal failure if mannitol administration continues. 1, 2

Recognition and Diagnosis

Monitor the osmolal gap rather than serum osmolality alone when using mannitol infusions, as this is the most reliable early indicator of mannitol accumulation and impending renal injury. 2

• Mannitol-induced AKI typically develops within 3-4 days of therapy, after cumulative doses averaging 626g in patients with normal baseline renal function 2
• In patients with pre-existing renal compromise, AKI can occur after much lower cumulative doses (approximately 295g) 2
• Key diagnostic features include: oliguric renal failure, elevated osmolal gap (typically >55 mOsm/kg), and renal tubular epithelial cells containing vacuoles in urinary sediment 2
• The FDA warns that reversible oliguric AKI has occurred even in patients with normal pretreatment renal function 1

Immediate Management

Stop mannitol infusion immediately if urine output declines or AKI develops. 1

• Initiate hemodialysis or extracorporeal ultrafiltration (ECUM) to remove accumulated mannitol 2, 3
• Renal function typically improves rapidly upon mannitol discontinuation and/or dialytic removal 2
• Monitor for complications of mannitol accumulation including severe dilutional hyponatremia with hyperosmolality, congestive heart failure, and volume overload 3
• Correct fluid and electrolyte imbalances, particularly hypernatremia and hyponatremia 1

Prevention Strategies

Mannitol is contraindicated in patients with oligoanuria and should be avoided in those with pre-existing renal disease. 4, 5

High-Risk Populations to Avoid Mannitol:

• Patients with oligoanuria (absolute contraindication) 4, 5
• Patients with pre-existing renal disease or conditions that increase renal failure risk 1
• Patients receiving nephrotoxic drugs (aminoglycosides) or other diuretics 1
• Patients with obstructive uropathy or hypovolemia 5
• Patients receiving radiocontrast agents (mannitol actually worsens contrast-induced nephropathy) 6

Monitoring Protocol When Mannitol Use is Unavoidable:

• Calculate osmolal gap (measured osmolality minus calculated osmolality) at baseline and during therapy 2
• Discontinue mannitol if osmolal gap exceeds 55 mOsm/kg 2
• Monitor serum sodium and potassium carefully during administration 1
• Ensure serum osmolality does not exceed 320 mOsm/L 4
• Use a filter when infusing 25% mannitol 1
• Closely monitor urine output and suspend infusion if output declines 1

Clinical Context and Evidence Quality

The evidence demonstrates that mannitol provides no additional benefit beyond adequate hydration for AKI prevention in most clinical scenarios. 6

• A 2014 meta-analysis of 626 patients found mannitol infusion does not reduce serum creatinine levels compared with volume expansion alone 6
• For contrast-induced nephropathy specifically, mannitol is detrimental (increases serum creatinine by 17.90 mg/dL) 6
• In malignant MCA infarction, mannitol emerged as an independent predictor of AKI (OR 5.02) with 39.8% of mannitol-treated patients developing AKI versus 11.9% of controls 7
• In high-dose cisplatin chemotherapy, mannitol addition to hydration did not reduce AKI risk and showed a trend toward increased risk 8

Limited Exception:

• Mannitol may reduce AKI incidence in renal transplant recipients (RR 0.34, NNT 3.03), though this requires further validation 6

Special Considerations

In rhabdomyolysis, mannitol may only benefit patients with creatine kinase >30,000 U/L, but even this benefit remains undefined and mannitol must be used with extreme caution only after adequate volume expansion. 4, 5

• KDOQI guidelines emphasize that mannitol is contraindicated in oligoanuric patients even in the rhabdomyolysis setting 4
• Adequate crystalloid fluid resuscitation (0.9% saline at 1000 mL/h initially) is the primary intervention for crush injury, not mannitol 4
• Studies show little extra benefit to mannitol compared with crystalloid resuscitation alone in crush syndrome 4

Do not use mannitol for renal protection during aortic repairs or other high-risk surgical procedures, as it has not been demonstrated to provide renal protection. 5