How to manage a patient with elevated Keppra (levetiracetam) levels?

Management of Elevated Levetiracetam (Keppra) Level of 72 μg/mL

For a patient with an elevated levetiracetam level of 72 μg/mL, supportive care is the primary management approach, with consideration of hemodialysis in cases of significant toxicity or renal impairment. 1

Assessment of Toxicity

• Normal therapeutic range: 10-37 μg/mL
• Current level: 72 μg/mL (approximately 2-7 times therapeutic level)
• Key symptoms to assess:
  • Neurological: Somnolence, confusion, encephalopathy, depressed level of consciousness
  • Respiratory: Respiratory depression (may require intubation in severe cases)
  • Neuromuscular: Diminished deep tendon reflexes
  • Behavioral: Agitation, aggression

Management Algorithm

1. Immediate Interventions

• Airway management: Assess respiratory status; intubate if respiratory depression is present
• Gastric decontamination: Consider gastric lavage or induced emesis if recent ingestion (within 1-2 hours) 1
• Vital sign monitoring: Continuous monitoring of respiratory rate, oxygen saturation, blood pressure
• Neurological assessment: Perform frequent neurological checks using CARTOX-10 or age-appropriate assessment tools 2

2. Supportive Care

• IV hydration: Maintain euvolemia to support renal clearance
• Seizure precautions: Implement seizure precautions despite levetiracetam being an antiseizure medication
• Electrolyte monitoring: Check and correct any electrolyte abnormalities that may worsen neurological symptoms

3. Specific Interventions Based on Severity

• For mild toxicity (somnolence, mild confusion):

  • Supportive care only
  • Monitor for clinical improvement

• For moderate toxicity (significant CNS depression, no respiratory compromise):

  • Continue supportive care
  • Consider poison control center consultation
  • Serial levetiracetam levels to track elimination

• For severe toxicity (respiratory depression, coma):

  • Consider hemodialysis - removes approximately 50% of levetiracetam in 4 hours 1
  • Indications for hemodialysis:
    • Severe clinical toxicity
    • Significant renal impairment
    • Persistently high levetiracetam levels

Monitoring and Follow-up

• Serial levetiracetam levels: Monitor levels every 6-12 hours until trending down
• Expected elimination: Half-life of approximately 5-7 hours in overdose cases with normal renal function 3
• Clinical improvement markers:
  • Improving mental status
  • Resolution of respiratory depression
  • Return of normal reflexes

Medication Adjustments After Recovery

• Dose adjustment: Consider lower maintenance dose once patient recovers
• Alternative options: If toxicity was due to an adverse reaction rather than overdose, consider:
  • Valproate (20-30 mg/kg IV) 4
  • Other second-line agents as appropriate for seizure management

Important Considerations

• No specific antidote exists for levetiracetam overdose 1
• Recovery is typically rapid with appropriate supportive care 3
• Contact Poison Control Center for up-to-date management recommendations 1
• Avoid medications that cause CNS depression during recovery period 4

Pitfalls to Avoid

• Don't assume seizure activity in a patient with decreased consciousness on levetiracetam; toxicity itself can cause CNS depression
• Don't delay hemodialysis in patients with severe symptoms or renal impairment
• Don't restart at the same dose after recovery without reassessing the appropriate therapeutic dose
• Don't miss underlying causes of elevated levels (renal dysfunction, drug interactions, accidental or intentional overdose)

Most patients with levetiracetam levels in this range will recover completely with appropriate supportive care, and the elimination half-life suggests normalization of levels within 24-48 hours in patients with normal renal function.