What is the recommended dose of ketamine (anesthetic agent) for super refractory status epilepticus?

Ketamine Dosing for Super-Refractory Status Epilepticus

For super-refractory status epilepticus, ketamine should be initiated with a loading dose of 0.15-0.20 mg/kg IV, followed by a continuous infusion starting at 1-5 mg/kg/hour, with titration based on clinical and EEG response.

Recommended Dosing Protocol

Initial Dosing

• Loading dose: 0.15-0.20 mg/kg IV bolus 1
• Maintenance infusion: Start at 1 mg/kg/hour, titrating upward by 1 mg/kg/hour every 15 minutes as needed 1
• Maximum infusion rate: Up to 5 mg/kg/hour 1, 2

Evidence-Based Dosing Range

The clinical literature demonstrates considerable variation in effective ketamine dosing:

• Reported effective range: 0.45-2.1 mg/kg/hour in one retrospective series, with maximum daily doses of 1392-4200 mg 3
• Higher doses: Some patients required 2.5-15 mg/kg/hour for seizure control 4
• Median effective dose: Approximately 5 mg/kg/hour in prospective registry data 4

Critical Timing Considerations

Early initiation of ketamine is strongly associated with better outcomes. The evidence demonstrates a clear time-dependent efficacy:

• Efficacy at 3 days: 64% seizure control when refractory status epilepticus duration is ≤3 days 5
• Efficacy at 26.5 days: Only 32% seizure control when mean duration is 26.5 days 5
• Statistical significance: Earlier initiation correlates with higher efficacy (P = 0.047) 2

Ketamine should be initiated within 2-7 days of status epilepticus onset, with earlier administration preferred 2, 4.

Duration of Therapy

• Time to seizure cessation: Ranges from 4-28 days (mean 9.8 days) after ketamine initiation 3
• Majority respond quickly: 64% of patients achieved seizure cessation within one week 3
• Clinical response window: Most patients show clinical and/or electrographic seizure cessation within 48 hours of ketamine initiation 6
• Prolonged infusion trend: Longer duration of infusion may increase efficacy, though this did not reach statistical significance (P = 0.285) 2

Combination Therapy

Ketamine should be used as an adjunctive agent with other antiseizure medications, not as monotherapy:

• Patients typically receive 2-5 concurrent antiseizure medications 2
• Benzodiazepine combination: Six of seven patients received midazolam before or during ketamine infusion, which may enhance efficacy 2
• Ketamine was the last antiseizure drug added before resolution in 64% of cases 3

Hemodynamic Benefits

Unlike traditional anesthetic agents used for refractory status epilepticus, ketamine provides unique cardiovascular advantages:

• Vasopressor weaning: 85% of patients requiring vasopressors during early treatment were successfully weaned during ketamine infusion 3
• Hemodynamic stability: Uniformly associated with improved hemodynamic parameters 3

This contrasts sharply with propofol (42% hypotension requiring pressors) and pentobarbital (77% hypotension requiring pressors) 7.

Safety Profile

• Acute adverse effects: No acute adverse effects noted in the largest case series 3
• Hepatic effects: Temporary hepatic failure occurred in 1 of 7 patients (14%) in one series 2
• Respiratory support: Unlike propofol and pentobarbital, ketamine may not require mechanical ventilation in all cases, particularly for nonconvulsive status epilepticus 5

Important Caveats

Efficacy Variability

The most recent prospective registry data (2022) shows lower efficacy than earlier retrospective studies:

• Prospective data: 27% permanent seizure control 4
• Retrospective data: 28-96% efficacy rates 5, 4

This discrepancy likely reflects selection bias in retrospective studies, which may have included less severe cases or only patients who responded to ketamine 4.

Guideline Context

Critical limitation: Current major guidelines (American College of Emergency Physicians, American Academy of Pediatrics) do not specifically mention ketamine for super-refractory status epilepticus 7, 1. The established third-line agents remain:

• Midazolam infusion (0.15-0.20 mg/kg load, then 1 mg/kg/min) 1
• Propofol (2 mg/kg bolus, then 3-7 mg/kg/hour) 7, 1
• Pentobarbital (13 mg/kg bolus, then 2-3 mg/kg/hour) 7, 1

Ketamine should be considered when these conventional anesthetics fail or are contraindicated, particularly in hemodynamically unstable patients 3.

Special Population: Anti-NMDA Receptor Encephalitis

For super-refractory status epilepticus associated with anti-NMDA receptor encephalitis, ketamine has particular theoretical appeal as an NMDA receptor antagonist:

• Effective dose: 0.05 mg/kg/min infusion (equivalent to 3 mg/kg/hour) 6
• Response time: Clinical/electrographic seizure cessation in <48 hours 6
• Mechanism: Directly antagonizes the pathophysiologic target of the autoimmune process 6

Monitoring Requirements

• Continuous EEG monitoring to assess seizure cessation and guide dose titration 2
• Vital signs monitoring, particularly blood pressure and heart rate 1
• Hepatic function tests during prolonged infusion 2
• Prepare for respiratory support, though it may not be universally required 5