What medications to give to an adult patient with hypoxic-ischemic encephalopathy (HIE) who continues to exhibit clonic jerks after receiving Levetiracetam (Keppra) 500mg?

Management of Persistent Clonic Jerks in HIE After Levetiracetam 500mg

For an adult with hypoxic-ischemic encephalopathy experiencing ongoing clonic jerks after receiving only 500mg of levetiracetam, immediately administer a full loading dose of levetiracetam 30 mg/kg IV (approximately 2000-3000mg for an average adult) over 5 minutes, as the initial 500mg dose is grossly inadequate for seizure control. 1, 2

Why the Initial Dose Was Insufficient

• The 500mg dose represents only 7-10 mg/kg for an average adult, which is one-third to one-quarter of the evidence-based loading dose required for seizure control 2, 3
• The ESETT trial and ACEP guidelines establish that levetiracetam requires 30 mg/kg IV to achieve 68-73% efficacy in benzodiazepine-refractory seizures 1, 2
• Lower doses (<20 mg/kg) demonstrate equivalent seizure termination rates to higher doses but this still requires at least 1400-1500mg for a 70kg patient, not 500mg 3

Immediate Treatment Algorithm

Step 1: Complete the Levetiracetam Loading Dose

• Administer the remaining levetiracetam to reach 30 mg/kg total dose (subtract the 500mg already given) 2
• Infuse over 5 minutes via IV 1, 2
• No cardiac monitoring is required, as levetiracetam has minimal cardiovascular effects and 0% hypotension risk 1, 2

Step 2: If Seizures Persist After Full Levetiracetam Dose (60 minutes)

Add a second-line agent with a different mechanism of action:

Valproate 20-30 mg/kg IV over 5-20 minutes is the preferred choice because:

• 88% efficacy with 0% hypotension risk 1, 2
• Superior safety profile compared to fosphenytoin (which has 12% hypotension risk) 1, 2
• Can be safely combined with levetiracetam without significant pharmacokinetic interactions 2

Alternative: Fosphenytoin 20 mg PE/kg IV at maximum rate of 50 mg/min if valproate is contraindicated:

• 84% efficacy but requires continuous ECG and blood pressure monitoring 1, 2
• 12% risk of life-threatening hypotension 1

Step 3: If Refractory to Both Agents (Refractory Status Epilepticus)

Initiate continuous EEG monitoring and escalate to anesthetic agents 2:

Midazolam infusion (first choice for refractory SE):

• Loading dose: 0.15-0.20 mg/kg IV 2
• Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 2
• 80% efficacy with 30% hypotension risk 2
• Requires mechanical ventilation 2

Propofol (alternative):

• 2 mg/kg bolus, then 3-7 mg/kg/hour infusion 2
• 73% efficacy with 42% hypotension risk 2
• Shorter ventilation time (4 days vs 14 days with barbiturates) 2

Pentobarbital (most effective but highest risk):

• 13 mg/kg bolus, then 2-3 mg/kg/hour infusion 2
• 92% efficacy but 77% hypotension risk requiring vasopressors 2

Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone (e.g., rocuronium) as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 2
• Do not skip directly to third-line anesthetic agents until adequate doses of benzodiazepines and at least one second-line agent have been tried 2
• Ensure benzodiazepines were given first - if not already administered, give lorazepam 4 mg IV at 2 mg/min immediately, as benzodiazepines are Level A first-line treatment 1, 2

Simultaneous Critical Actions

• Check fingerstick glucose immediately and correct hypoglycemia 2
• Search for reversible causes: hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, intracerebral hemorrhage 1, 2
• Maintain continuous oxygen saturation monitoring with supplemental oxygen available 2
• Have airway equipment immediately available, as respiratory depression can occur with escalating therapy 2

Special Considerations for HIE Population

• In post-cardiac arrest HIE patients, myoclonic status epilepticus may indicate Lance-Adams syndrome, which paradoxically may be compatible with good neurological outcome and should not be treated overly aggressively 2
• However, ongoing clonic jerks require treatment to prevent secondary brain injury from continued seizure activity 1
• Continuous EEG monitoring is essential to distinguish true epileptic activity from non-epileptic myoclonus 2