What are the clinical considerations for a levetiracetam (Keppra) overdose?

Clinical Management of Levetiracetam (Keppra) Overdose

Levetiracetam overdose primarily causes CNS depression with somnolence and respiratory depression, but patients typically recover rapidly with supportive care alone, and hemodialysis should be considered for severe cases or significant renal impairment. 1

Primary Clinical Manifestations

The clinical presentation of levetiracetam overdose is characterized by:

• Somnolence and depressed level of consciousness are the most common findings, with obtundation occurring in severe cases 1, 2
• Respiratory depression requiring intubation can occur with significant overdoses (e.g., 30,000 mg ingestion resulted in respiratory depression necessitating mechanical ventilation) 2
• Agitation and aggression have been reported in postmarketing surveillance 1
• Coma may develop in severe overdoses 1
• Diminished deep tendon reflexes have been documented 2

Critical Monitoring Parameters

Continuous monitoring of vital signs and respiratory status is essential, as respiratory depression is the primary life-threatening complication:

• Monitor respiratory rate, oxygen saturation, and level of consciousness 1
• Assess airway protection capability, as obtundation may necessitate intubation 2
• Serial neurological assessments to track clinical trajectory 1

Management Algorithm

Immediate Stabilization

Airway management takes priority - intubate if the patient cannot protect their airway due to depressed consciousness 2:

• Ensure adequate oxygenation and ventilation 1
• Position patient to prevent aspiration 1
• Have resuscitation equipment immediately available 1

Decontamination Considerations

Gastric decontamination should only be attempted if the patient presents early and the airway is protected 1:

• Emesis or gastric lavage may be considered for recent ingestions if airway is secured 1
• Usual precautions must be observed to maintain airway patency 1
• Do not attempt if patient has depressed consciousness without airway protection 1

Supportive Care

General supportive care is the cornerstone of management, as there is no specific antidote for levetiracetam overdose 1:

• Maintain hemodynamic stability with IV fluids as needed 1
• Monitor vital signs continuously 1
• Observe clinical status closely for deterioration 1
• Contact a Certified Poison Control Center for up-to-date management guidance 1

Enhanced Elimination

Hemodialysis is highly effective and should be strongly considered in severe overdoses or patients with renal impairment 1:

• Standard hemodialysis removes approximately 50% of levetiracetam in 4 hours 1
• Consider hemodialysis based on clinical severity (profound CNS depression, respiratory failure) 1
• Particularly indicated in patients with significant renal impairment, as levetiracetam is primarily renally eliminated 1
• Although not performed in early reported cases, hemodialysis may be indicated by the patient's clinical state 1

Pharmacokinetic Considerations

Levetiracetam demonstrates first-order elimination even at supratherapeutic concentrations 2:

• Therapeutic serum concentration: 10-37 mcg/mL 2
• Reported overdose concentration: 400 mcg/mL at 6 hours post-ingestion (10-40 fold higher than therapeutic) 2
• Elimination half-life in overdose: approximately 5.14 hours 2
• Rapid clinical recovery typically occurs within 24 hours with supportive care 2

Prognostic Factors

The prognosis is generally excellent with appropriate supportive care 2:

• Recovery without sequelae is typical, even after massive overdoses 2
• Extubation often possible within 24 hours 2
• Fatalities are rare with appropriate respiratory support 2
• Two fatal cases with elevated levetiracetam levels (190 and 35 mg/L) involved polydrug ingestions 3

Critical Pitfalls to Avoid

Do not delay respiratory support while awaiting laboratory confirmation - manage based on clinical presentation 1, 2:

• CNS depression and respiratory compromise require immediate intervention regardless of drug levels 2
• Do not assume benign course in obtunded patients - secure airway early 2
• Avoid medications that cause additional CNS depression during management 4
• Do not discharge patients until fully alert and respiratory function is stable 2

Special Populations

Pediatric cases have been reported with levetiracetam concentrations ranging from 1.4 to 50 mg/L 3:

• Children may require the same aggressive airway management as adults 3
• Supportive care principles remain identical across age groups 1