How should I acutely treat and subsequently manage a patient who presents with a seizure?

Acute Seizure Management

For any patient actively seizing, immediately administer IV lorazepam 4 mg at 2 mg/min—this is your first-line treatment with 65% efficacy in terminating status epilepticus. 1

Immediate Actions (0-5 Minutes)

First-Line Treatment: Benzodiazepines

• Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient (≥5 minutes duration) 1, 2
• Lorazepam is superior to diazepam (65% vs 56% success rate) with longer duration of action 1
• Check fingerstick glucose simultaneously and correct hypoglycemia—a rapidly reversible cause 1
• Have airway equipment immediately available before administration, as respiratory depression can occur 1

Alternative routes if IV access unavailable:

• IM midazolam 0.2 mg/kg (maximum 6 mg) if IV access is challenging 1
• Intranasal midazolam with onset within 1-2 minutes, peak effect at 3-4 minutes 1
• IV diazepam if lorazepam unavailable 1

Critical Simultaneous Actions

• Establish IV access and start fluid resuscitation to prevent hypotension 1
• Search for reversible causes: hypoglycemia, hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, intracerebral hemorrhage, withdrawal syndromes 1, 3
• Maintain continuous oxygen saturation monitoring with supplemental oxygen available 1

---

Second-Line Treatment (5-20 Minutes)

If seizures continue after adequate benzodiazepine dosing, immediately escalate to one of these second-line agents—do not delay. 1

Preferred Second-Line Agents (Choose One)

Valproate is the optimal choice with superior efficacy and safety profile:

• Dose: 20-30 mg/kg IV over 5-20 minutes 1
• 88% efficacy with 0% hypotension risk (superior to fosphenytoin's 84% efficacy with 12% hypotension) 1
• No cardiac monitoring required 1
• Contraindicated in women of childbearing potential due to teratogenicity and neurodevelopmental risks 1
• Contraindicated in liver disease 3

Levetiracetam is an excellent alternative, especially for elderly or hemodynamically unstable patients:

• Dose: 30 mg/kg IV (approximately 2000-3000 mg for average adult) over 5 minutes 1
• 68-73% efficacy with minimal cardiovascular effects 1
• No cardiac monitoring required 1
• Favorable side effect profile with fewer drug interactions 3
• Requires renal dose adjustment in kidney dysfunction 1

Fosphenytoin (traditional option, now less preferred):

• Dose: 20 mg PE/kg IV at maximum rate of 50 mg/min 1
• 84% efficacy but 12% hypotension risk 1
• Requires continuous ECG and blood pressure monitoring 1
• 95% of neurologists still use this for benzodiazepine-refractory seizures 1

Phenobarbital (reserve for specific situations):

• Dose: 20 mg/kg IV over 10 minutes 1
• 58.2% efficacy as initial second-line agent 1
• Higher risk of respiratory depression and hypotension 1

Key Evidence

The ESETT trial found comparable efficacy between levetiracetam (47%), fosphenytoin (45%), and valproate (46%), allowing medication selection based on patient-specific factors rather than efficacy alone. 4, 3 However, valproate's superior safety profile (0% vs 12% hypotension) makes it the preferred choice when not contraindicated. 1

---

Refractory Status Epilepticus (20+ Minutes)

Define refractory status epilepticus as seizures continuing despite benzodiazepines and one second-line agent—initiate continuous EEG monitoring at this stage. 1

Third-Line Anesthetic Agents (Choose One)

Midazolam infusion (first-choice anesthetic):

• Loading dose: 0.15-0.20 mg/kg IV 1
• Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
• 80% overall success rate 1
• 30% hypotension risk (lowest among anesthetics) 1
• Load with phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital during the infusion to ensure adequate long-acting anticonvulsant levels before tapering 1

Propofol (alternative for intubated patients):

• Bolus: 2 mg/kg, then infusion 3-7 mg/kg/hour 1
• 73% efficacy with 42% hypotension risk 1
• Requires mechanical ventilation but shorter duration (4 days vs 14 days with barbiturates) 1
• Continuous blood pressure monitoring essential 1

Pentobarbital (most effective but highest risk):

• Bolus: 13 mg/kg, then infusion 2-3 mg/kg/hour 1
• 92% efficacy (highest) but 77% hypotension risk requiring vasopressors 1
• Prolonged mechanical ventilation (mean 14 days) 1
• Reserve for super-refractory cases 1

Critical Monitoring for Refractory Status Epilepticus

• Continuous EEG monitoring throughout treatment and for 24-48 hours after discontinuation 1
• Breakthrough seizures occur in >50% of patients and are often only detectable by EEG 1
• Have vasopressors immediately available (norepinephrine or phenylephrine) as hypotension is common 1
• Confirm mechanical ventilation is established before initiating anesthetic agents 1

---

Subsequent Management After Seizure Control

For Patients with Known Epilepsy

• Continue or optimize current antiepileptic medication 3
• Verify medication compliance by checking serum drug levels 1
• Search for precipitating factors: sleep deprivation, alcohol use, medication non-compliance, intercurrent illness 1
• Question patient about seizure occurrences at each follow-up visit 1

For First-Time Seizure (Single, Self-Limited)

• No evidence supports loading with anticonvulsant medication after a single resolved seizure 2
• Most seizures are self-limited and resolve spontaneously within 1-2 minutes 2
• Stay with patient and monitor for return to baseline mental status within 5-10 minutes 2
• Activate EMS if patient does not return to baseline within 5-10 minutes or if another seizure occurs 2
• Obtain EEG and brain imaging (preferably epilepsy-specific MRI) to characterize etiology and recurrence risk 5

Maintenance Dosing After Status Epilepticus

Levetiracetam maintenance:

• Convulsive status epilepticus: 30 mg/kg IV every 12 hours (maximum 1500 mg) 1
• Non-convulsive status epilepticus: 15 mg/kg IV every 12 hours (maximum 1500 mg) 1

Valproate maintenance:

• Continue at therapeutic levels based on clinical response 3

---

Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone (e.g., rocuronium)—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1
• Never skip to third-line agents until benzodiazepines and a second-line agent have been tried 1
• Never put anything in the patient's mouth during seizures—this is a Class 3 Harm recommendation 2
• Do not use intramuscular diazepam due to erratic absorption—use rectal route instead 1
• Do not attribute altered mental status solely to post-ictal state—obtain urgent EEG if patient does not awaken within expected timeframe, as nonconvulsive status epilepticus occurs in >50% of cases 1
• Avoid valproate in women of childbearing potential due to teratogenicity 1, 3
• Do not delay anticonvulsant administration for neuroimaging in active status epilepticus—CT can be performed after seizure control 1