What is the approach to managing a patient presenting with a seizure, considering their past medical history and current antiepileptic medication regimen, such as carbamazepine (anticonvulsant) or valproate (anticonvulsant)?

Approach to a Case of Seizure

Initial Stabilization and Assessment

For any patient actively seizing, immediately administer IV lorazepam 4 mg at 2 mg/min as first-line treatment, which has 65% efficacy in terminating status epilepticus. 1, 2

• Check fingerstick glucose immediately while administering treatment, as hypoglycemia is a rapidly reversible cause 2
• Ensure airway equipment is immediately available before administering benzodiazepines due to respiratory depression risk 2
• Establish IV access and begin fluid resuscitation simultaneously with benzodiazepine administration 2
• Monitor oxygen saturation with supplemental oxygen available 2

Critical Immediate Diagnostic Evaluation

Simultaneously search for reversible causes while treating the seizure, including hypoglycemia, hyponatremia, hypocalcemia, hypomagnesemia, hypoxia, drug toxicity, CNS infection, stroke, intracerebral hemorrhage, and withdrawal syndromes. 2, 3

• Obtain serum glucose, sodium, calcium, and magnesium immediately, as these metabolic derangements lower seizure threshold 2, 3
• Women of reproductive age require pregnancy test to rule out eclampsia 4
• Consider thyroid function tests if hyperthyroidism is suspected, as this can precipitate seizures 3

Classification: First Seizure vs. Known Epilepsy

For First Unprovoked Seizure (Patient Returned to Baseline)

Emergency physicians need not initiate antiepileptic medication in the ED for patients who have had an unprovoked first seizure without evidence of brain disease or injury. 1

• Approximately one-third to one-half of patients with a first unprovoked seizure will have recurrence within 5 years, but initiating treatment within days to weeks after a seizure prolongs time to subsequent event without changing 5-year outcomes 1
• The number needed to treat (NNT) to prevent a single seizure recurrence within the first 2 years is 14 patients 1
• Emergency physicians may initiate antiepileptic medication in the ED, or defer in coordination with other providers, for patients who experienced a first unprovoked seizure with a remote history of brain disease or injury (stroke, trauma, tumor), as seizure recurrence rate is substantially higher in these patients. 1

For Provoked Seizure

Emergency physicians need not initiate antiepileptic medication in the ED for patients who have had a provoked seizure—instead, identify and treat precipitating medical conditions. 1

• Common precipitants include metabolic derangements, drug toxicity, alcohol withdrawal, CNS infection, and acute stroke 2

Benzodiazepine-Refractory Seizures: Second-Line Treatment

If seizures continue after adequate benzodiazepine dosing (two doses of lorazepam 4 mg), immediately escalate to one of the following second-line agents with equivalent efficacy (45-49% seizure cessation at 60 minutes): 2, 5

Preferred Second-Line Options (in order of preference based on safety profile):

1. Levetiracetam 30 mg/kg IV (approximately 2000-3000 mg for average adult) over 5 minutes

   • 68-73% efficacy with minimal cardiovascular effects (0.7% hypotension, 0.7% arrhythmias) 2, 5
   • No cardiac monitoring required, making it ideal for elderly patients 5
   • Preferred in elderly due to minimal drug interactions and favorable side effect profile 5

2. Valproate 20-30 mg/kg IV over 5-20 minutes

   • 88% efficacy with 0% hypotension risk 2
   • Contraindicated in patients with liver disease or women of childbearing potential due to teratogenicity and hepatotoxicity 2, 3
   • Superior safety profile compared to phenytoin but requires liver function monitoring 2

3. Fosphenytoin 20 mg PE/kg IV at maximum rate of 50 mg/min (or 150 PE/min)

   • 84% efficacy but 12% hypotension risk requiring continuous ECG and blood pressure monitoring 2, 5
   • Traditional and most widely available second-line agent, with 95% of neurologists recommending it for benzodiazepine-refractory seizures 2

4. Phenobarbital 20 mg/kg IV over 10 minutes

   • 58.2% efficacy but higher risk of respiratory depression and hypotension 2
   • Reserve for situations where other agents are unavailable or contraindicated 2

Refractory Status Epilepticus (Seizures Continue Despite Benzodiazepines + One Second-Line Agent)

Initiate continuous EEG monitoring at this stage and select one of the following anesthetic agents: 2

First-Choice Anesthetic Agent:

Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 2

• 80% overall success rate with 30% hypotension risk 2
• Lower hypotension risk compared to pentobarbital (77%) and higher efficacy than propofol (73%) 2
• Load with phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital during midazolam infusion to ensure adequate long-acting anticonvulsant levels before tapering 2

Alternative Anesthetic Agents:

Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion

• 73% efficacy with 42% hypotension risk 2
• Requires mechanical ventilation but shorter ventilation time than barbiturates (4 days vs 14 days) 2
• Continuous blood pressure monitoring essential 2

Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion

• Highest efficacy at 92% but 77% hypotension risk requiring vasopressors 2
• Prolonged mechanical ventilation (mean 14 days) 2
• Reserve for cases refractory to midazolam and propofol 2

Management of Patients Already on Antiepileptic Medications

For Breakthrough Seizure on Current Regimen (e.g., Carbamazepine or Valproate):

Obtain serum drug levels immediately to assess compliance and adequate dosing, as non-compliance is the most common cause of breakthrough seizures. 2

• Search for precipitating factors: sleep deprivation, alcohol use, medication non-compliance, intercurrent illness, drug interactions 2
• Consider EEG to distinguish true epileptic seizures from psychogenic seizures or detect subclinical seizure activity 2
• Optimize current medication dosing before adding another agent 2

If Seizures Remain Uncontrolled Despite Adequate Monotherapy:

For patients on levetiracetam with inadequate control, adding valproate 20-30 mg/kg is a reasonable combination strategy, as both agents have similar efficacy (46-47% seizure control) as second-line monotherapy and can be safely combined without significant pharmacokinetic interactions. 2

• Monitor liver function tests due to valproate's hepatotoxicity risk 2
• Avoid valproate in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay 2
• Alternative adjuncts include lamotrigine or lacosamide 2

Drug Interactions to Consider:

Enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) increase valproate clearance, requiring higher doses and more frequent monitoring. 6

• Valproate may displace protein-bound drugs (phenytoin, carbamazepine, warfarin, tolbutamide) 6
• Carbamazepine clearance is affected by concurrent medications; avoid MAOIs within 14 days and nefazodone 7

Disposition Decisions

Emergency physicians need not admit patients with a first unprovoked seizure who have returned to their clinical baseline in the ED. 1

• Patients with comorbidities, focal neurologic examination, or who have not returned to normal baseline mental status require extensive diagnostic evaluation including non-contrast head CT in the ED 4
• Adults with first-time seizure, no comorbidities, and normal baseline require only serum glucose and electrolyte determination 4
• Neuroimaging should not delay anticonvulsant administration in active status epilepticus; CT scanning can be performed after seizure control is achieved 2

Critical Pitfalls to Avoid

Never use neuromuscular blockers alone (such as rocuronium), as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury. 2

• Do not skip to third-line agents (pentobarbital) until benzodiazepines and a second-line agent have been tried 2
• Do not stop antiepileptic medications abruptly, as this can precipitate status epilepticus in patients with epilepsy 7
• Do not attribute all symptoms to seizure disorder alone when underlying conditions (such as hyperthyroidism) may be present 3
• Recognize that recurrent seizures may signal underlying disease relapse (thyroid disease, metabolic derangement) rather than antiepileptic drug failure 3

Special Population Considerations

Elderly Patients:

Start antiepileptic medications at lower doses (25-50% of standard adult doses) and titrate more slowly than in younger adults, with close monitoring for cognitive impairment, dizziness, and ataxia which increase fall risk. 5

• Levetiracetam and lamotrigine are first-line options due to favorable side effect profiles and fewer drug interactions 5
• Protein binding of valproate is reduced in elderly, increasing free fraction and requiring dose adjustments 2, 6
• Risk of structural lesions (stroke, tumor) increases to 34-40% in patients over 60 years old 5