What is the appropriate evaluation and management for a 48‑year‑old man presenting with generalized tonic‑clonic seizure activity and altered mental status?

Evaluation and Management of a 48-Year-Old Male with Generalized Tonic-Clonic Seizure and Altered Mental Status

Administer intravenous lorazepam 4 mg at 2 mg/min immediately—this terminates status epilepticus in approximately 65% of cases and is the strongest evidence-based first-line treatment. 1

Immediate Stabilization (0-5 Minutes)

Airway and Safety:

• Have airway equipment (bag-valve-mask, intubation set) immediately available before administering any benzodiazepine due to respiratory depression risk 1
• Establish continuous oxygen saturation monitoring 2
• Secure IV access and begin fluid resuscitation to prevent hypotension 1
• Check fingerstick glucose immediately—hypoglycemia is a rapidly reversible cause that must be corrected emergently 1

First-Line Treatment:

• Lorazepam 4 mg IV at 2 mg/min is superior to diazepam (59.1% vs 42.6% seizure cessation) and has longer duration of action 1
• If IV access unavailable, use intramuscular midazolam 10 mg (equivalent efficacy to IV lorazepam) 1
• Status epilepticus is defined as seizure activity ≥5 minutes or recurrent seizures without return to baseline 1, 2

Second-Line Treatment (5-20 Minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of the following second-line agents (do not delay for neuroimaging): 1

Preferred agent—Valproate:

• 30 mg/kg IV (maximum 3000 mg) over 5-20 minutes 1, 2
• 88% efficacy with 0% hypotension risk 1, 2
• Absolute contraindication in women of childbearing potential due to teratogenicity 1

Alternative—Levetiracetam:

• 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes 1, 2
• 68-73% efficacy with minimal cardiovascular effects (≈0.7% hypotension) 1, 2
• No cardiac monitoring required 1
• 20% intubation rate 1

Traditional option—Fosphenytoin:

• 20 mg PE/kg IV at maximum rate of 150 PE/min 1, 3
• 84% efficacy but 12% hypotension risk 1, 2
• Requires continuous ECG and blood pressure monitoring 2
• 26.4% intubation rate 1

Reserve option—Phenobarbital:

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

The 2019 ESETT trial showed no significant efficacy difference between levetiracetam, fosphenytoin, and valproate (45-47% seizure cessation), so selection should prioritize safety profile and contraindications rather than efficacy alone. 1

Simultaneous Evaluation for Reversible Causes

While administering anticonvulsants, immediately assess for: 1, 2

• Hypoglycemia (point-of-care glucose mandatory) 1
• Hyponatremia (most common electrolyte disturbance causing seizures) 1
• Hypoxia 1, 2
• Drug toxicity or withdrawal (alcohol, benzodiazepines, barbiturates) 1, 2
• CNS infection (meningitis, encephalitis) 1, 2
• Acute stroke or intracerebral hemorrhage (especially in patients >40 years) 1

Laboratory workup:

• Serum sodium, complete metabolic panel 1
• Antiepileptic drug levels if known epilepsy 1
• Toxicology screen based on clinical presentation 1

Neuroimaging Strategy

Obtain emergent non-contrast head CT if any of the following are present: 1

• First-time seizure 1
• Focal neurological deficits 1
• Persistent altered mental status 1
• Fever with concern for CNS infection 1
• Head trauma history 1
• Known or suspected malignancy 1
• Anticoagulation use 1

Critical pitfall: Do not delay anticonvulsant administration to obtain neuroimaging in active status epilepticus—CT can be performed after seizure control and stabilization. 1

Refractory Status Epilepticus (20+ Minutes)

Definition: Seizures continuing despite adequate benzodiazepines AND one second-line agent. 1, 2

Initiate continuous EEG monitoring at this stage (nonconvulsive status epilepticus occurs in up to 25% of cases). 1, 2

Third-line anesthetic agents:

First choice—Midazolam infusion:

• Loading dose: 0.15-0.20 mg/kg IV 1, 2
• Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1, 2
• 80% efficacy with 30% hypotension risk 1, 2
• Load a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) before tapering midazolam 2

Alternative—Propofol:

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

Highest efficacy—Pentobarbital:

• 13 mg/kg bolus, then 2-3 mg/kg/hour infusion 1, 2
• 92% efficacy but 77% hypotension risk requiring vasopressors 1, 2
• Mean mechanical ventilation duration 14 days 1, 2

EEG Monitoring

Obtain emergent EEG for: 1, 2

• Persistent altered consciousness after seizure (to detect nonconvulsive status epilepticus) 1, 2
• Refractory status epilepticus (to guide anesthetic titration) 1, 2
• Patients who received long-acting paralytics 1
• Drug-induced coma 1

Nonconvulsive status epilepticus cannot be diagnosed by clinical observation alone—EEG confirmation is mandatory. 1, 4

Prognosis

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