IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures

More than one in every one hundred patients presenting to the emergency department for care do so for seizures. More than half of these patients will require medications, often intravenously (IV), while in the emergency department. For many years the standard treatment has been phenytoin. However, there are many known contraindications to the use of this drug. These include known hypersensitivity, cardiac arrhythmias, cardiac disease, impaired liver or kidney function, diabetes mellitus, older age, thyroid disease, pregnancy, and alcohol use. A recent review of patients with seizure disorder at Emory Crawford Long and Emory University hospitals suggested that a significant percentage of those who were taking phenytoin actually had one or more of these contraindications. Additionally, the IV form of phenytoin has known, severe adverse effects including cardiovascular collapse, life threatening cardiac arrhythmias, and severe hypotension. There is another form of Phenytoin, called Fosphenytoin, that while safer in some respects still has similar concerns associated with its administration.

Levetiracetam (Keppra) has been available as an oral drug in the United States since 2000 and has a well established safety record when used as an add-on drug for patients with partial onset seizures. A double-blinded randomized study has shown that levetiracetam is also effective for primary generalized seizures as well.

The IV form of levetiracetam has recently been approved by the FDA for use. The only known contraindications other than known hypersensitivity include impaired renal function, psychiatric disorder, older age, and pregnancy. IV levetiracetam is not known to cause any of the acute, catastrophic events seen occasionally with phenytoin.

The investigators would therefore like to compare IV phenytoin and fosphenytoin to IV levetiracetam in preventing early recurrent seizures. Patients with known seizure disorders would be randomly assigned to one of two groups and therefore receive either IV fosphenytoin or IV levetiracetam. After an observation period, seizure free patients would be discharged and 24 hour phone follow up conducted to assess for the effectiveness of these anti-seizure medications as well as for any adverse reactions.

• Drug: Keppra
  The patient will receive 1 gram of Keppra added to 100ml diluent and will be infused over 15 minutes.
  Other Name: levetiracetam
• Drug: Fosphenytoin
  IV load will be dependant on dilantin level. If no dilantin is detected in the patient, the patient will receive 1 gram of IV Fosphenytoin infused at 15 mg/min or slower depending on vitals.
  Other Name: Cerebyx
• Drug: Dilantin
  IV load will be dependant on dilantin level. If no dilantin is detected in the patient, the patient will receive 1 gram of IV phenytoin infused at 25 mg/min or slower depending on vitals.
  Other Name: phenytoin

• Active Comparator: Phenytoin/Fosphenytoin
  Patients in the control arm will receive either IV Dilantin (1 gram of IV phenytoin infused at 25 mg/min or slower depending on vitals) or IV Fosphenytoin (1 gram of IV Fosphenytoin infused at 15 mg/min or slower depending on vitals).
  Interventions:

  • Drug: Fosphenytoin
  • Drug: Dilantin
• Active Comparator: Levetiracetam
  Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes).
  Intervention: Drug: Keppra

Inclusion Criteria:

• age 18 or older
• patient presenting to Grady Memorial Hospital's Emergency Department after having a tonic-clonic seizure (primary or secondarily generalized) within the last 4 hours

Cause of seizure for inclusion: reason for seizure is often undetermined at time of presentation to the Emergency Department. The most likely expected causes of a seizure are noncompliance to existing antiepileptic drug regimen, refractory epilepsy with breakthrough seizure, metabolic aberration, alcohol withdrawal, or unknown.

Exclusion Criteria:

• non-English speaking
• first time seizure
• seizures other than tonic-clonic seizure (primary or secondarily generalized)
• more than 3 seizures in 24 hours or status epilepticus, pregnant patients by history or by urine pregnancy testing, serious neurologic insult resulting in seizure but where seizure is not the primary reason for admission (e.g. traumatic brain injury with seizure or hemorrhagic stoke would be excluded)
• contraindication to IV levetiracetam
• received IV phenytoin within 24 hours
• known allergy to phenytoin
• previously enrolled in the study