What is the appropriate emergency treatment and dosing for an acute seizure in a non‑pregnant adult?

Emergency Treatment and Dosing for Acute Seizure in Non-Pregnant Adults

First-Line Treatment: Benzodiazepines

Administer intravenous lorazepam 4 mg at a rate of 2 mg/min immediately for any actively seizing patient; this terminates status epilepticus in approximately 65% of cases and is superior to diazepam (59.1% vs 42.6% seizure cessation). 1

• Lorazepam is preferred over diazepam because of its longer duration of action and higher efficacy 1
• A second dose of lorazepam 4 mg may be given after at least 1 minute if seizures persist, with a maximum of two total doses 1
• Have airway equipment (bag-valve-mask, intubation set) immediately available before administering any benzodiazepine, as respiratory depression is a predictable adverse effect 1
• Maintain continuous oxygen saturation monitoring throughout treatment 1

Alternative Benzodiazepine Routes (when IV access unavailable)

• Intramuscular midazolam 10 mg provides efficacy equivalent to intravenous lorazepam and is easier to administer in the pre-hospital setting 1, 2
• Intranasal midazolam has onset of action within 1–2 minutes, with peak effect at 3–4 minutes 1
• Rectal diazepam 0.5 mg/kg should be used if buccal/intranasal routes are not feasible 1
• Do not use intramuscular diazepam due to erratic absorption—use rectal route instead 1

Definition of Status Epilepticus

Status epilepticus is defined as any seizure lasting ≥5 minutes or recurrent seizures without regaining consciousness between episodes; treatment should begin immediately at this threshold. 1

Second-Line Anticonvulsants (if seizures persist after adequate benzodiazepine dosing)

If seizures continue after two doses of lorazepam, immediately escalate to one of the following second-line agents without delay: 1

Valproate (Preferred for Safety Profile)

• Dose: 20–30 mg/kg IV (maximum 3000 mg) infused over 5–20 minutes 1
• Efficacy: 88% seizure cessation with 0% hypotension risk 1
• Absolute contraindication: Women of childbearing potential due to fetal teratogenicity 1
• No cardiac monitoring required 1

Levetiracetam (Excellent Alternative)

• Dose: 30 mg/kg IV (maximum 2500–3000 mg) over 5 minutes 1
• Efficacy: 68–73% seizure cessation 1
• Minimal cardiovascular effects (≈0.7% hypotension risk) 1
• Intubation rate approximately 20% 1
• No cardiac monitoring required 1

Fosphenytoin (Traditional Option)

• Dose: 20 mg PE/kg IV at maximum rate of 150 PE/min (or 50 mg/min in adults) 1, 3
• Efficacy: 84% seizure cessation but 12% hypotension risk 1
• Requires continuous ECG and blood pressure monitoring 1, 3
• Intubation rate approximately 26% 1
• Administer directly into large peripheral or central vein through large-gauge catheter 3
• Follow each injection with sterile saline flush to avoid local venous irritation 3
• Can be diluted with normal saline; avoid dextrose-containing solutions due to precipitation 3

Phenobarbital (Reserve Option)

• Dose: 20 mg/kg IV over 10 minutes (maximum 1000 mg) 1
• Efficacy: 58.2% seizure cessation as initial second-line agent 1
• Higher risk of respiratory depression and hypotension due to vasodilatory and cardiodepressive effects 1

Evidence from ESETT Trial

The 2019 Established Status Epilepticus Treatment Trial demonstrated no statistically significant difference in efficacy among levetiracetam, fosphenytoin, and valproate (seizure cessation rates 47%, 45%, and 46% respectively); therefore, selection should prioritize safety profile and contraindications rather than efficacy alone. 1

Refractory Status Epilepticus (≥20 minutes despite benzodiazepines and one second-line agent)

Refractory status epilepticus requires immediate ICU transfer, continuous EEG monitoring, and escalation to anesthetic agents. 1

Midazolam Infusion (First Choice)

• Loading dose: 0.15–0.20 mg/kg IV 1
• Maintenance infusion: start at 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
• Efficacy: 80% seizure control; hypotension in approximately 30% of cases 1
• Load with a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) before tapering midazolam to ensure adequate coverage 1

Propofol (Alternative for Intubated Patients)

• Loading dose: 2 mg/kg IV bolus 1
• Maintenance infusion: 3–7 mg/kg/hour 1
• Efficacy: 73% seizure control; hypotension in approximately 42% of cases 1
• Requires mechanical ventilation but shorter duration than barbiturates (average 4 days vs 14 days) 1

Pentobarbital (Highest Efficacy, Highest Complication Rate)

• Loading dose: 13 mg/kg IV 1
• Maintenance infusion: 2–3 mg/kg/hour 1
• Efficacy: 92% seizure control but 77% hypotension risk requiring vasopressor support 1
• Mean mechanical ventilation duration of 14 days 1

Maintenance Dosing After Seizure Control

Lorazepam

• 0.05 mg/kg IV (maximum 1 mg) every 8 hours for three doses 1

Levetiracetam

• Convulsive status epilepticus: 30 mg/kg IV every 12 hours OR increase prophylactic dose by 10 mg/kg (to 20 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

Phenobarbital

• 1–3 mg/kg IV every 12 hours 1

Phenytoin/Fosphenytoin

• After loading, transition to oral phenytoin 300–400 mg per day divided into multiple doses 1

Simultaneous Critical Actions

While administering anticonvulsants, immediately identify and treat reversible causes: 1

• Check fingerstick glucose immediately and correct hypoglycemia 1
• Assess for hyponatremia (most common electrolyte disturbance causing seizures) 1
• Evaluate for hypoxia, drug toxicity or withdrawal (alcohol, benzodiazepines, barbiturates) 1
• Consider CNS infection, acute stroke, or intracerebral hemorrhage 1
• Do not postpone anticonvulsant therapy to obtain neuroimaging 1

Monitoring Requirements

• Continuous oxygen saturation monitoring with supplemental oxygen available 1
• Continuous ECG and blood pressure monitoring when using fosphenytoin or phenytoin 1, 3
• Continuous EEG monitoring in refractory status epilepticus to guide anesthetic titration and detect ongoing electrical seizure activity 1
• Continue EEG monitoring for at least 24–48 hours after drug discontinuation, as approximately 25% of patients have ongoing non-convulsive electrical seizures 1

Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1
• Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried 1
• Avoid intramuscular phenytoin due to risk of necrosis, abscess formation, and erratic absorption 3
• Do not abruptly discontinue long-term antiepileptic medications, as this can precipitate withdrawal seizures 4

Prognosis

Overall mortality for status epilepticus ranges from 5% to 22%; in refractory cases mortality can reach 65%, underscoring the critical importance of rapid, aggressive treatment. 1