In post‑cardiac‑arrest patients, is levetiracetam (Keppra) required for seizure prophylaxis?

Levetiracetam (Keppra) is NOT Recommended for Seizure Prophylaxis After Cardiac Arrest

Do not use seizure prophylaxis in post-cardiac arrest patients. 1 This recommendation is clear and consistent across the most recent and authoritative guidelines.

The Evidence Against Prophylaxis

The 2025 European Resuscitation Council and European Society of Intensive Care Medicine guidelines explicitly state that seizure prophylaxis should not be used in post-cardiac arrest patients 1. This position has remained consistent since at least 2015, when guidelines noted that "routine seizure prophylaxis in post-cardiac arrest patients is not recommended because of the risk of adverse effects and the poor response to anti-epileptic agents among patients with clinical and electrographic seizures" 2.

The 2020 International Consensus on CPR reinforces this, noting there are no RCTs specifically designed to evaluate the impact of post-cardiac arrest seizure prophylaxis on neurological outcomes 3. The 2025 AHA guidelines confirm that seizure prophylaxis did not improve outcomes after cardiac arrest in prospective trials and was not effective in preventing subsequent seizures 4.

When to Treat Seizures (Not Prevent Them)

If seizures actually occur, then treatment is indicated:

• Use EEG to diagnose seizures in patients with clinical convulsions and to monitor treatment effects 1
• First-line treatment: Use levetiracetam OR sodium valproate as first-line antiepileptic drugs in addition to sedative drugs to treat seizures after cardiac arrest 1
• Avoid phenytoin/fosphenytoin: These agents cause more hypotension and need for intubation compared to levetiracetam or valproate 3

Why Prophylaxis Causes Harm

The rationale against prophylaxis is multifactorial:

• Adverse effects without benefit: Prophylactic antiseizure medications are associated with adverse events and poor functional outcomes without preventing seizures 4
• Confounds prognostication: Sedation and high-dose antiepileptic drugs delay awakening, prolong mechanical ventilation, and confound neurological examination, leading to overly pessimistic prognostication 3
• Most patients already receive sedatives: Comatose post-arrest patients routinely receive propofol or benzodiazepines that have antiepileptic effects 3

Clinical Approach

Your algorithm should be:

1. Do not start prophylactic antiseizure medications in any post-cardiac arrest patient
2. Monitor with EEG if clinical seizures are suspected or observed
3. If seizures are confirmed on EEG, initiate treatment with:
   • Levetiracetam (preferred) OR sodium valproate
   • Continue sedatives (propofol/benzodiazepines) which also suppress seizures
4. For myoclonus with benign EEG background, attempt a wake-up trial days after arrest rather than aggressive treatment 1

Important Caveats

• Approximately one-third of comatose post-arrest patients develop seizures 2, so vigilance is required
• Electrographic status epilepticus may occur without clinical manifestations, especially in sedated patients 2
• Some patients with myoclonus and epileptiform discharges may have Lance-Adams syndrome, which is compatible with good outcomes—overly aggressive treatment may not be warranted 3
• The 2023 ILCOR review found no high-certainty evidence that antiepileptic drugs improve outcomes in post-cardiac arrest patients with seizures 3

Bottom line: Reserve levetiracetam for treatment of documented seizures, not for prophylaxis. The evidence consistently shows no benefit and potential harm from prophylactic use in this population.