Ketamine for Seizures

 

Ketamine for Seizures Summary

During long seizures, GABA receptors (the target of traditional drugs) are internalized and become less effective, while NMDA receptors are upregulated. Ketamine targets these upregulated NMDA receptors to blunt excitatory signals. By blocking glutamate-mediated excitotoxicity, Ketamine may help prevent brain damage during intense, prolonged seizures. Research into Ketamine use for seizures focuses on its role in treating severe, prolonged seizures that do not respond to standard medications. a When looking at 19 different studies, ketamine achieved seizure resolution in 53-91% of cases. A 2025 study in a pediatric emergency department found that 76% of children receiving a ketamine-midazolam combination achieved seizure cessation in five minutes, compared to only 21% for those who only got medizolam. Another 2024 study found that 84% of patients had their seizure burden reduced by 50% within 24 hours.

Note: Ketamine has not yet officially been approved for treating seizures by the FDA, so its use is considered "off-label" and should only be done under supervision of a physician.

1) Mechanism of Action

Ketamine has been investigated as a treatment for refractory seizures, especially status epilepticus that does not respond to conventional therapies.

  • Noncompetitive NMDA receptor antagonism
  • Reduction of excitatory glutamate signaling
  • Suppression of sustained neuronal hyperexcitability
  • Prevention of excitotoxic neuronal injury

During prolonged seizures, GABA receptor sensitivity decreases while NMDA-mediated excitation increases. Ketamine targets this NMDA pathway, which may help when GABAergic medications become less effective.

2) Clinical Indications

  • Refractory status epilepticus (RSE)
  • Super-refractory status epilepticus (SRSE)
  • Seizures persisting despite:
    • Benzodiazepines
    • Antiepileptic drugs
    • Anesthetic agents

3) Clinical Effects

  • Terminates persistent seizure activity
  • Reduces neuronal hyperexcitability
  • Provides neuroprotection against excitotoxic damage
  • Can sometimes decrease seizure frequency when other anesthetics fail

4) Methods of Administration

Ketamine for seizures is usually administered in intensive care settings.

  • Intravenous bolus followed by continuous infusion
  • Infusion is titrated based on EEG monitoring

Continuous EEG monitoring is typically used to evaluate seizure suppression.

5) Potential Advantages

  • Different mechanism of action: NMDA blockade
  • May remain effective when GABAergic drugs fail
  • Relatively less respiratory depression than some sedatives
  • Often preserves hemodynamic stability

These properties can make ketamine useful in severe refractory seizure states.

6) Limitations and Risks

  • Optimal dosing strategies are still evolving
  • Usually requires ICU-level monitoring
  • Potential adverse neuropsychiatric effects

7) Adverse Effects

  • Hypertension
  • Tachycardia
  • Increased secretions
  • Dissociation or hallucinations during recovery
  • Sedation
  • Increased intracranial pressure (historically debated)

8) Current Clinical Role

Ketamine is most commonly used in:

  • Refractory status epilepticus
  • Super-refractory status epilepticus

This is usually after seizures continue despite multiple anticonvulsant and anesthetic treatments.