What is the appropriate acute workup and initial management for an adult presenting with a seizure?

Acute Seizure Workup and Initial Management in Adults

Immediately administer IV lorazepam 4 mg at 2 mg/min for any actively seizing patient, while simultaneously checking fingerstick glucose and establishing airway equipment at bedside. This first-line benzodiazepine therapy terminates status epilepticus in 65% of cases and is superior to diazepam (59.1% vs 42.6% efficacy). 1, 2

Immediate Stabilization (0-5 Minutes)

Critical First Actions

• Administer IV lorazepam 4 mg at 2 mg/min as the definitive first-line treatment for active seizures 1, 2, 3
• Check fingerstick glucose immediately and correct hypoglycemia with IV dextrose if present 2, 4
• Have airway equipment (bag-valve-mask, intubation set) immediately available before giving any benzodiazepine due to respiratory depression risk 2, 3
• Establish IV access and begin fluid resuscitation to maintain euvolemia 3, 4
• Initiate continuous monitoring: vital signs, oxygen saturation, ECG, and blood pressure 3, 4

Alternative Benzodiazepine Routes (if IV access unavailable)

• IM midazolam 10 mg (equivalent efficacy to IV lorazepam) 1
• Intranasal midazolam with onset in 1-2 minutes 2
• Rectal diazepam 0.5 mg/kg if other routes not feasible 2, 3

Status Epilepticus Definition

Status epilepticus is defined as any seizure lasting ≥5 minutes or recurrent seizures without return to baseline—treatment must begin immediately at this threshold, not the historical 30-minute definition. 1, 2, 5

Second-Line Treatment (5-20 Minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to valproate as the preferred second-line agent due to its superior safety profile. 1, 2, 4

Recommended Second-Line Agents (in order of safety profile)

Valproate (preferred):

• Dose: 30 mg/kg IV over 5-20 minutes (maximum 3000 mg) 2, 3, 4
• Efficacy: 88% seizure control with 0% hypotension risk 1, 2, 4
• Absolute contraindication: Women of childbearing potential due to teratogenicity 2, 3

Levetiracetam (excellent alternative):

• Dose: 30 mg/kg IV over 5 minutes (maximum 2500-3000 mg) 1, 2, 3, 4
• Efficacy: 68-73% seizure control 1, 2, 4
• Advantages: Minimal cardiovascular effects (0.7% hypotension), no cardiac monitoring required, 20% intubation rate 2, 4

Fosphenytoin (traditional option):

• Dose: 20 mg PE/kg IV at maximum rate of 150 PE/min 1, 2, 3, 4
• Efficacy: 84% seizure control but 12% hypotension risk 1, 2, 4
• Requires continuous ECG and blood pressure monitoring 1, 2
• Intubation rate: 26.4% 4

Phenobarbital (reserve option):

• Dose: 20 mg/kg IV over 10 minutes 1, 2, 3
• Efficacy: 58.2% as initial second-line agent 1, 2
• Higher risk of respiratory depression and hypotension 1, 2

Key Evidence

The 2019 ESETT trial (Level I evidence) demonstrated no significant efficacy difference between levetiracetam, fosphenytoin, and valproate (47%, 45%, and 46% seizure cessation respectively), so agent selection should prioritize safety profile and contraindications rather than efficacy. 1, 2, 4

Simultaneous Evaluation for Reversible Causes

While administering anticonvulsants, immediately search for and treat underlying etiologies—do not delay treatment to obtain neuroimaging. 1, 2, 4

Critical Reversible Causes to Identify

• Hypoglycemia (check fingerstick immediately) 2, 4
• Hyponatremia (most common electrolyte disturbance causing seizures) 2, 6
• Hypoxia 1, 2
• Drug toxicity or withdrawal (alcohol, benzodiazepines, barbiturates) 1, 2, 6
• CNS infection (meningitis, encephalitis) 1, 2
• Acute stroke or intracerebral hemorrhage (especially age >40) 2
• Toxins (theophylline, isoniazid, cocaine) 7, 6

Laboratory Workup for First-Time Seizure

Essential Laboratory Tests

Only serum glucose and sodium consistently change acute ED management and require immediate measurement. 2

• Fingerstick glucose (immediate) 2, 4
• Serum sodium (most common metabolic cause) 2, 6
• Pregnancy test in all patients of childbearing potential 2

Additional Labs (based on clinical context)

• Complete metabolic panel if metabolic derangement suspected 6
• Toxicology screen if drug ingestion or withdrawal suspected 7, 6
• Antiepileptic drug levels in patients with known epilepsy 1

Neuroimaging Strategy

Emergent Non-Contrast Head CT Indications

Perform emergent CT when ANY high-risk feature is present (CT abnormalities found in 23-41% of first-time seizures): 2

• Age >40 years 2
• Recent head trauma 2
• Focal seizure onset 2
• Fever or persistent headache 2
• Anticoagulation use 2
• Known malignancy or immunocompromised state 2
• Focal neurologic deficit 2
• Persistent altered mental status 2

Outpatient MRI

If patient has returned to baseline, normal neurologic exam, no high-risk features, and reliable follow-up, neuroimaging can be deferred to outpatient MRI (more sensitive for temporal and orbitofrontal epileptogenic lesions). 2

Refractory Status Epilepticus (20+ Minutes)

Refractory status epilepticus is defined as seizures continuing despite benzodiazepines and one second-line agent—initiate continuous EEG monitoring and anesthetic agents at this stage. 1, 2, 3

Third-Line Anesthetic Agents

Midazolam infusion (first choice):

• Loading: 0.15-0.20 mg/kg IV 1, 2, 3, 4
• Maintenance: 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1, 2, 3
• Efficacy: 80% seizure control with 30% hypotension risk 1, 2, 3
• Load with long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, or levetiracetam) during infusion before tapering 2, 3

Propofol (alternative for intubated patients):

• Loading: 2 mg/kg bolus 1, 2, 3, 4
• Maintenance: 3-7 mg/kg/hour infusion 1, 2, 3, 4
• Efficacy: 73% seizure control with 42% hypotension risk 1, 2, 3
• Requires mechanical ventilation but shorter duration than barbiturates (4 days vs 14 days) 1, 2

Pentobarbital (highest efficacy but most complications):

• Loading: 13 mg/kg 1, 2, 3
• Maintenance: 2-3 mg/kg/hour infusion 1, 2, 3
• Efficacy: 92% seizure control but 77% hypotension risk requiring vasopressors 1, 2, 3
• Mean 14 days mechanical ventilation 1, 2

Critical Monitoring for Refractory Cases

• Continuous EEG monitoring to guide anesthetic titration and detect ongoing electrical seizure activity 1, 2, 3, 4
• Continuous blood pressure monitoring with vasopressors immediately available 2, 3
• Mechanical ventilation readiness 2, 3
• Continue EEG for minimum 24-48 hours after anesthetic discontinuation (nonconvulsive seizures occur in >50% of cases) 2

Electroencephalography (EEG) Indications

Emergent EEG

Obtain emergent EEG when altered consciousness persists after seizure to detect nonconvulsive status epilepticus (occurs in ~25% of patients with generalized convulsive status epilepticus). 2, 4

Outpatient EEG

Arrange outpatient EEG for every patient after a first unprovoked seizure because abnormal EEG predicts higher seizure recurrence risk. 2

Disposition Decisions

Safe for Discharge

Patients who have returned to clinical baseline in the ED can be safely discharged without admission if: 2

• Normal neurologic examination 2
• No abnormal investigation results requiring inpatient management 2
• Reliable outpatient follow-up arranged 2

Admission Criteria

• Persistent abnormal neurologic examination 2
• Abnormal investigation results requiring inpatient management 2
• Failure to return to baseline 2
• Unreliable follow-up or social concerns 2

Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 2, 3
• Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried 2, 3
• Do not delay anticonvulsant administration to obtain neuroimaging in active status epilepticus 2, 4
• Phenytoin is ineffective for alcohol withdrawal seizures, theophylline toxicity, and isoniazid toxicity 6
• Avoid valproate in women of childbearing potential due to fetal malformations and neurodevelopmental delay 2, 3

Prognosis

Overall mortality for status epilepticus ranges from 5-22%, rising to 65% in refractory cases—emphasizing the critical importance of rapid, aggressive treatment. 1, 2