What is the role of ketamine in the treatment of status epilepticus?

Role of Ketamine in the Treatment of Status Epilepticus

Ketamine is recommended as a treatment option for refractory status epilepticus (RSE) after failure of benzodiazepines and second-line anticonvulsants, with increasing evidence supporting its earlier use in the treatment algorithm. 1

Standard Treatment Algorithm for Status Epilepticus

• First-line treatment should be benzodiazepines (e.g., midazolam, lorazepam, diazepam) 2, 3
• Second-line options include:
  • Valproate IV (30 mg/kg at 5-6 mg/kg/min) - 88% efficacy with minimal hypotension risk 2, 3
  • Phenytoin/Fosphenytoin IV (20 mg/kg at max 50 mg/min) - requires cardiac monitoring due to higher hypotension risk (12%) 2, 3
  • Levetiracetam IV (30 mg/kg, max 2500 mg) - 68-73% efficacy with favorable safety profile 2, 3

Ketamine's Position in Status Epilepticus Treatment

• Traditionally used in refractory status epilepticus (RSE) when seizures persist despite first and second-line treatments 4, 1
• Mechanism: Non-competitive NMDA receptor antagonist, which addresses the pathophysiological shift from GABA-mediated to glutamate-mediated seizure activity in prolonged status epilepticus 5
• Dosing range: 0.45-2.1 mg/kg/hour as continuous infusion, with reported daily doses of 1392-4200 mg 6

Evidence Supporting Ketamine Use

• Ketamine has demonstrated efficacy in terminating RSE in multiple case series, with seizure cessation occurring within 4-28 days (mean 9.8 days) after initiation 6
• In one case series, ketamine was the last antiepileptic drug added before seizure resolution in 64% of cases 6
• Recent evidence suggests potential benefit as an advanced second-line agent rather than waiting until seizures become super-refractory 1, 5
• A case report documented successful termination of status epilepticus in a pediatric patient with a single 1 mg/kg IV dose of ketamine after failure of multiple conventional treatments 7

Advantages of Ketamine

• Provides hemodynamic stability - 85% of patients requiring vasopressors in one study were able to be weaned during ketamine infusion 6
• May have neuroprotective properties based on animal models 5
• Shows synergistic effects with other antiseizure medications 5
• Can be considered for induction during rapid sequence intubation in patients requiring airway protection, providing dual benefit 7

Limitations and Considerations

• Limited by lack of large randomized controlled trials specifically for status epilepticus 1, 5
• Should be used as part of a comprehensive approach that includes identifying and treating underlying causes (hypoglycemia, hyponatremia, infections, toxicity) 2, 3
• Continuous EEG monitoring is essential when treating status epilepticus to confirm treatment success, as transition to non-convulsive status is common 4

Practical Application

• Consider ketamine earlier in treatment algorithm for refractory cases, particularly when:
  • Hemodynamic instability is present 6
  • Conventional second-line agents have failed 1, 5
  • Patient requires intubation for airway protection 7
• Initial bolus of 1-2 mg/kg followed by continuous infusion at 0.45-2.1 mg/kg/hour based on clinical response 7, 6