What is the recommended acute management for an inpatient with epilepsy who is experiencing ongoing seizures?

Managing Epilepsy Patient Inpatient

For an inpatient experiencing ongoing seizures, immediately administer IV lorazepam 4 mg at 2 mg/min as first-line therapy, followed by a second-line agent (valproate 20-30 mg/kg IV, levetiracetam 30 mg/kg IV, or fosphenytoin 20 mg PE/kg IV) if seizures persist beyond 5 minutes, and escalate to continuous anesthetic infusions (midazolam, propofol, or pentobarbital) for refractory status epilepticus. 1, 2

Immediate Recognition and Stabilization (0-5 minutes)

Status epilepticus is defined as any seizure lasting ≥5 minutes or recurrent seizures without return to baseline consciousness between episodes. 1, 2 This operational definition has replaced the traditional 30-minute threshold because delayed treatment significantly worsens outcomes, with mortality rates of 5-22% in treated cases and up to 65% in refractory cases. 1, 2

Critical Pre-Treatment Actions

• Have airway equipment (bag-valve-mask, intubation set) immediately available before administering any benzodiazepine, as respiratory depression is a predictable adverse effect requiring intervention. 1, 3
• Check fingerstick glucose immediately—hypoglycemia is a rapidly reversible cause that must be corrected simultaneously with seizure treatment. 1
• Establish IV access and begin continuous vital sign monitoring, including oxygen saturation and blood pressure. 1
• Do not delay anticonvulsant administration to obtain neuroimaging; CT can be performed after seizure control is achieved. 1

First-Line Treatment: Benzodiazepines

Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient. 1, 3 Lorazepam is the preferred benzodiazepine with 65% efficacy in terminating status epilepticus and superior performance compared to diazepam (59.1% vs 42.6% seizure cessation). 1 Lorazepam also has a longer duration of action than other benzodiazepines, reducing the risk of seizure recurrence. 1, 4

• If seizures continue after 10-15 minutes, administer a second 4 mg dose of lorazepam. 3
• Continuously monitor for respiratory depression; apnea can occur up to 30 minutes after the last dose. 1
• Prepare for mechanical ventilation if needed, as respiratory support may be required regardless of administration route. 1

Alternative Routes When IV Access Unavailable

• IM midazolam 0.2 mg/kg (maximum 6 mg) if IV access is delayed, with similar efficacy to IV diazepam (97% relative efficacy). 1
• Intranasal midazolam provides rapid systemic delivery with onset in 1-2 minutes and peak effect at 3-4 minutes. 1
• Rectal diazepam 0.5 mg/kg if buccal/intranasal routes are not feasible. 1

Common Pitfall: Do not use intramuscular diazepam due to erratic absorption—use rectal route instead if IM administration is being considered. 1

Second-Line Treatment: IV Anticonvulsants (5-20 minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of the following second-line agents. 1, 2 The choice depends on patient-specific factors, availability, and safety profile:

Valproate (Preferred for Safety Profile)

• Dose: 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes 1, 2
• Efficacy: 88% seizure control with 0% hypotension risk 1
• Valproate demonstrates superior safety compared to phenytoin (88% vs 84% efficacy; 0% vs 12% hypotension risk). 1, 2
• Does not require continuous cardiac monitoring. 1
• Absolute contraindication: Women of childbearing potential due to fetal teratogenic risk. 1

Levetiracetam (Preferred for Minimal Cardiovascular Effects)

• Dose: 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes 1, 2
• Efficacy: 68-73% seizure control with minimal adverse effects 1
• Hypotension risk approximately 0.7% with 20% intubation rate. 1
• No cardiac monitoring required, making it ideal for elderly patients or those with cardiovascular disease. 1
• Can be diluted in 100 mL NS and administered over 5-15 minutes. 1

Fosphenytoin (Traditional Agent, Requires Monitoring)

• Dose: 20 mg PE/kg IV at maximum rate of 150 PE/min 1, 2
• Efficacy: 84% seizure control but 12% hypotension risk 1
• Requires continuous ECG and blood pressure monitoring due to cardiovascular toxicity. 1, 2
• 95% of neurologists recommend phenytoin/fosphenytoin for benzodiazepine-refractory seizures, reflecting widespread availability. 1
• Intubation rate 26.4%. 1

Phenobarbital (Higher Risk Profile)

• Dose: 20 mg/kg IV over 10 minutes (maximum 1000 mg) 1, 2
• Efficacy: 58.2% as initial second-line agent 1
• Higher risk of respiratory depression and hypotension compared to other options. 1, 2
• Reserve for cases where other agents are contraindicated or unavailable. 1

Clinical Decision Algorithm:

• First choice: Valproate (unless woman of childbearing potential) or levetiracetam (if cardiovascular concerns)
• Second choice: Fosphenytoin (if valproate/levetiracetam unavailable)
• Last resort: Phenobarbital (if all other agents contraindicated)

Simultaneous Evaluation for Reversible Causes

While administering anticonvulsants, immediately search for and treat underlying etiologies: 1, 2

• Metabolic: Hypoglycemia (most common correctable cause), hyponatremia (most common electrolyte disturbance precipitating seizures), hypoxia 1, 2
• Toxic: Drug toxicity, alcohol or benzodiazepine withdrawal syndromes 1, 2
• Structural: CNS infection, ischemic stroke, intracerebral hemorrhage (especially in patients >40 years) 1, 2
• Medication-related: Subtherapeutic antiepileptic drug levels, non-compliance 1

Refractory Status Epilepticus (20+ minutes)

Refractory status epilepticus is defined as seizures continuing despite benzodiazepines and one adequate second-line agent. 1 At this stage, initiate continuous EEG monitoring and escalate to anesthetic agents. 1

Midazolam Infusion (First-Choice Anesthetic)

• Loading dose: 0.15-0.20 mg/kg IV 1, 2
• Maintenance: 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
• Efficacy: 80% seizure control with 30% hypotension risk 1
• Before tapering midazolam, load with a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) to ensure adequate levels are established. 1

Propofol (Alternative Anesthetic)

• Loading dose: 2 mg/kg bolus 1, 2
• Maintenance: 3-7 mg/kg/hour infusion 1
• Efficacy: 73% seizure control with 42% hypotension risk 1
• Requires mechanical ventilation but shorter duration than barbiturates (4 days vs 14 days). 1
• Useful in intubated patients without hypotension. 1

Pentobarbital (Most Effective but Highest Risk)

• Loading dose: 13 mg/kg 1
• Maintenance: 2-3 mg/kg/hour infusion 1
• Efficacy: 92% seizure control but 77% hypotension risk requiring vasopressors 1
• Prolonged mechanical ventilation (mean 14 days). 1
• Reserve for cases refractory to midazolam and propofol. 1

Critical Pitfall: Never use neuromuscular blockers (e.g., rocuronium) alone—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury. 1

Continuous EEG Monitoring

Initiate continuous EEG monitoring for all patients with refractory status epilepticus, persistent altered consciousness, or those receiving anesthetic agents. 1, 2

• Approximately 25% of patients with generalized convulsive status epilepticus have ongoing non-convulsive electrical seizures detectable only by EEG. 1
• EEG should guide titration of anesthetic agents to achieve seizure suppression (typically burst-suppression pattern). 1
• Continue EEG monitoring for at least 24-48 hours after complete anesthetic discontinuation, as late seizure recurrence is common and often nonconvulsive. 1
• Breakthrough seizures occur in >50% of patients during tapering and are often only detectable by EEG without clinical manifestations. 1

Maintenance Therapy After Seizure Control

Once seizures are controlled, transition to maintenance antiepileptic therapy: 1

Levetiracetam Maintenance

• Convulsive status epilepticus: 30 mg/kg IV every 12 hours (maximum 1500 mg per dose) 1
• Non-convulsive status epilepticus: 15 mg/kg IV every 12 hours (maximum 1500 mg per dose) 1
• Adjust doses in renal dysfunction based on creatinine clearance. 1

Phenytoin/Fosphenytoin Maintenance

• 300-400 mg oral phenytoin daily divided into multiple doses after IV loading to maintain therapeutic levels. 1

Valproate Maintenance

• Continue at therapeutic doses with monitoring of liver function tests due to hepatotoxicity risk. 1

Special Monitoring Considerations

• Continuous vital sign monitoring is essential, particularly respiratory status and blood pressure. 1
• Have vasopressors immediately available (norepinephrine or phenylephrine) as hypotension is common with anesthetic agents. 1
• Confirm mechanical ventilation is established before initiating anesthetic therapy. 1
• Do not attribute altered mental status solely to post-ictal state—obtain urgent EEG if patient does not awaken within expected timeframe, as non-convulsive status epilepticus occurs in >50% of cases. 1

Neuroimaging Indications

Obtain emergent non-contrast head CT when any high-risk feature is present: 1

• Age >40 years
• Recent head trauma
• Focal seizure onset or focal neurological deficits
• Fever or persistent headache
• Anticoagulation use
• Known malignancy or immunocompromised state
• Persistent altered mental status

CT abnormalities are identified in 23-41% of first-time seizure presentations. 1 However, do not delay anticonvulsant administration to obtain imaging—stabilize the patient first. 1