What is the next step in managing post-operative seizures in a patient who has undergone mitral valve repair and maze procedure, with ongoing seizures despite two doses of Keppra (levetiracetam) and recent cessation of Propofol (propofol), with negative CT scans and normal electrolyte levels?

Post-Operative Seizure Management After Cardiac Surgery

Immediate Next Steps

Add valproate (20-30 mg/kg IV over 5-20 minutes) as your second-line agent, as it demonstrates 88% efficacy with minimal hypotension risk (0% vs 12% with phenytoin) and is particularly effective when levetiracetam has failed. 1, 2

Alternatively, you may add phenobarbital (20 mg/kg IV over 10 minutes) or fosphenytoin (20 mg PE/kg IV at maximum 50 mg/min), though these carry higher risks of respiratory depression and hypotension respectively. 1, 2

Critical Diagnostic Considerations

Obtain continuous EEG monitoring immediately to distinguish between:

• True epileptic seizures requiring escalation of antiepileptic therapy
• Non-epileptic myoclonus (common post-cardiac surgery, occurs in 18-25% of post-cardiac arrest patients)
• Propofol withdrawal seizures
• Subclinical status epilepticus (detected in 23-31% of comatose patients with continuous EEG) 1

The negative CT scans help exclude structural causes like intracranial hemorrhage or stroke, but do not rule out metabolic or epileptic etiologies. 1

Treatment Algorithm for Refractory Seizures

If seizures persist after second-line agent:

Transfer to ICU and initiate treatment for refractory status epilepticus: 1, 2

1. Midazolam infusion: 0.15-0.20 mg/kg IV loading dose, followed by continuous infusion at 1 mg/kg/min, titrating up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1, 2

2. Propofol: 2 mg/kg bolus followed by 3-7 mg/kg/hour infusion (note: propofol is effective for suppressing post-anoxic myoclonus and may already be familiar in your post-cardiac surgery setting, though it requires mechanical ventilation) 1, 2

3. Pentobarbital: 13 mg/kg bolus followed by 2-3 mg/kg/hour infusion (92% efficacy but higher hypotension risk than propofol) 2

Specific Considerations for Your Case

The timing of seizures with propofol cessation raises two important possibilities:

• Propofol withdrawal seizures: Propofol itself suppresses seizure activity, and abrupt cessation can unmask underlying seizures or lower seizure threshold 1, 2

• Inadequate levetiracetam dosing: Two doses of Keppra may be insufficient. Standard loading is 30-40 mg/kg IV (maximum 2500-4500 mg), followed by maintenance dosing of 15-30 mg/kg IV every 12 hours 1, 3

Post-cardiac surgery patients have unique risk factors:

• Cerebral hypoperfusion during bypass
• Microemboli
• Inflammatory response
• Electrolyte shifts (though you've ruled this out)
• The maze procedure itself involves atrial ablation, which shouldn't directly cause seizures but indicates complex cardiac pathology 1

Monitoring Requirements

Continuous monitoring must include: 1

• Continuous EEG to detect subclinical seizures and guide therapy
• Continuous cardiac monitoring (ECG) and blood pressure, especially with phenytoin/fosphenytoin administration
• Respiratory status with readiness for intubation (higher intubation rates occur with levetiracetam >40 mg/kg dosing) 3
• Serial neurological examinations to assess for improvement

Common Pitfalls to Avoid

Do not assume all motor activity is epileptic seizure - post-anoxic myoclonus and other non-epileptic movements are common after cardiac surgery and may not respond to standard antiepileptics. 1

Do not use phenytoin/fosphenytoin as first choice in this setting - while effective (84% efficacy), it carries 12% hypotension risk and requires cardiac monitoring, which is particularly concerning in post-cardiac surgery patients. 1, 2

Do not delay continuous EEG - visual confirmation of seizure activity is unreliable, and you may be treating non-epileptic movements or missing subclinical status epilepticus. 1

Avoid underdosing levetiracetam - if continuing levetiracetam, ensure adequate loading (30-40 mg/kg) was given, not just "two doses." 1, 3

Underlying Cause Investigation

Simultaneously search for and treat reversible causes: 2

• Hypoglycemia (recheck despite normal electrolytes)
• CNS infection (consider LP if no contraindications)
• Ischemic stroke or hemorrhage (repeat imaging if clinical deterioration)
• Drug toxicity or withdrawal syndromes
• Cerebral hypoxia during surgery