How to manage a patient with a history of seizures on valproic acid and Vimpat who had seizures before and during transport to the hospital after receiving intranasal Versed?

Management of Refractory Seizures in a Patient on Valproic Acid and Lacosamide

For a patient with history of seizures on valproic acid and Vimpat (lacosamide) who continues to have seizures despite receiving intranasal midazolam, additional IV benzodiazepines should be administered followed by IV valproic acid, levetiracetam, or fosphenytoin as second-line therapy. 1

Initial Assessment and Management

• Assess and secure airway, breathing, and circulation while simultaneously evaluating for treatable causes of status epilepticus including hypoglycemia, hyponatremia, hypoxia, drug toxicity, and systemic or CNS infection 1
• Check vital signs and perform rapid neurological assessment during post-ictal phase 1
• Obtain blood glucose level immediately 1
• Consider the seizure as potentially refractory since the patient has already received intranasal midazolam (Versed) and continued to seize 1

Medication Management Algorithm

Step 1: Optimize Benzodiazepine Therapy

• Despite receiving 5 mg intranasal midazolam from family, administer IV benzodiazepines as first-line therapy since the patient had a subsequent seizure 1
• Options include:
  • IV lorazepam 4 mg at 2 mg/min 1
  • IV diazepam 5-10 mg at 5 mg/min 1

Step 2: Second-line Therapy (if seizures continue)

• Administer one of the following agents (all have similar efficacy according to current guidelines) 1:
  • IV valproic acid 20-40 mg/kg at 3-6 mg/kg/min (preferred option since patient is already on oral valproic acid) 1
  • IV levetiracetam 60 mg/kg (up to 4500 mg) 1
  • IV fosphenytoin 20 mg PE/kg at 150 mg PE/min 1

Step 3: If Seizures Continue Despite Second-line Therapy

• Consider intubation for airway protection and administration of:
  • Propofol 1
  • Midazolam infusion 1
  • Phenobarbital 1

Special Considerations for This Patient

• Since the patient is already on valproic acid and lacosamide, check serum levels of both medications to determine if subtherapeutic levels are contributing to breakthrough seizures 2
• Be aware of potential drug interactions between valproic acid and lacosamide that may affect serum levels 3
• Monitor for valproic acid toxicity, which can be exacerbated by concurrent lacosamide use 3
• Consider checking ammonia levels, as valproic acid can cause hyperammonemic encephalopathy 3

Monitoring and Follow-up

• Continuous cardiac and oxygen saturation monitoring during and after medication administration 1
• Monitor for hypotension, particularly with fosphenytoin (12% risk) versus valproic acid (minimal risk) 1
• Observe for respiratory depression, especially with additional benzodiazepine administration 1
• Consider EEG monitoring if available, particularly if mental status does not improve after clinical seizure cessation 1

Important Cautions

• Avoid phenytoin/fosphenytoin if possible in patients already on valproic acid, as valproic acid displaces phenytoin from plasma protein binding sites and inhibits its metabolism, potentially leading to phenytoin toxicity 2
• Be cautious with additional benzodiazepines after the patient has already received midazolam due to risk of respiratory depression 1
• Monitor for cardiac arrhythmias and hypotension, especially with rapid infusion of antiepileptic medications 1