What is the appropriate acute and subsequent management for a patient presenting with a seizure?

Acute Management of Seizures

For an actively seizing patient, immediately administer IV lorazepam 4 mg at 2 mg/min, which terminates status epilepticus in approximately 65% of cases and is superior to diazepam. 1 If IV access is unavailable, give IM midazolam 10 mg, which has equivalent efficacy. 1

Definition and Time-Critical Action

• 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 at the traditional 30-minute mark. 1, 2
• Have airway equipment immediately available before administering any benzodiazepine due to respiratory depression risk. 1
• Check fingerstick glucose immediately and correct hypoglycemia while administering treatment. 1

First-Line Treatment (0-5 Minutes)

Benzodiazepines are Level A first-line therapy:

• Lorazepam 4 mg IV at 2 mg/min is preferred over diazepam (59.1% vs 42.6% seizure cessation) due to longer duration of action. 1
• IM midazolam 10 mg if IV access is delayed—provides equivalent efficacy to IV lorazepam. 1
• Prepare for respiratory support; monitor oxygen saturation continuously for at least 30 minutes after administration. 1

Second-Line Treatment (5-20 Minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of the following agents (the 2019 ESETT trial showed similar efficacy for all three at 45-47%, so selection should prioritize safety profile): 1

Valproate (Preferred for Safety Profile)

• Dose: 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes
• Efficacy: 88% seizure control with 0% hypotension risk—superior safety compared to phenytoin. 1
• Absolute contraindication: Women of childbearing potential due to teratogenicity. 1

Levetiracetam (Excellent Alternative)

• Dose: 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes
• Efficacy: 68-73% with minimal cardiovascular effects (≈0.7% hypotension, 20% intubation rate). 1
• No cardiac monitoring required; safe in elderly and renal dysfunction (with dose adjustment). 1

Fosphenytoin (Traditional Option)

• Dose: 20 mg PE/kg IV at maximum rate of 150 PE/min
• Efficacy: 84% but 12% hypotension risk—requires continuous ECG and blood pressure monitoring. 1
• Intubation rate 26.4%; slower administration than alternatives. 1

Phenobarbital (Reserve Option)

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

Refractory Status Epilepticus (20+ Minutes)

Defined as seizures continuing despite benzodiazepines AND one second-line agent—initiate continuous EEG monitoring at this stage. 1

Midazolam Infusion (First Choice)

• Loading: 0.15-0.20 mg/kg IV; Maintenance: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min
• Efficacy: 80% with 30% hypotension risk—lowest hypotension rate among anesthetic agents. 1
• Critical: Load a long-acting anticonvulsant (phenytoin, valproate, levetiracetam, or phenobarbital) before tapering midazolam to prevent breakthrough seizures. 1

Propofol (Alternative for Intubated Patients)

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

Pentobarbital (Highest Efficacy, Highest Risk)

• Dose: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion
• Efficacy: 92% but 77% hypotension risk—requires vasopressor support and mean 14 days mechanical ventilation. 1

Concurrent Evaluation for Reversible Causes

While administering anticonvulsants, immediately search for and treat:

• Hypoglycemia and hyponatremia—the only metabolic abnormalities that consistently alter acute management. 3, 4
• Hypoxia, drug toxicity or withdrawal (alcohol, benzodiazepines, barbiturates). 1
• CNS infection—consider lumbar puncture (after CT) in immunocompromised patients or those with fever and meningeal signs. 3
• Acute stroke or intracerebral hemorrhage—especially in patients >40 years. 3
• Do not delay anticonvulsant therapy to obtain neuroimaging. 1

Subsequent Management After Seizure Control

Laboratory Evaluation

• Serum glucose and sodium are mandatory—these are the only tests that consistently change acute management. 3, 4
• Pregnancy test in all women of childbearing age. 3, 4
• Additional metabolic panels (calcium, magnesium) only if clinical clues present (vomiting, diarrhea, known renal disease, malignancy). 3

Neuroimaging Decision Algorithm

Emergent non-contrast head CT is indicated for:

• Age >40 years
• Recent head trauma
• Focal seizure onset or focal neurological deficits
• Persistent altered mental status
• Fever or persistent headache
• Anticoagulation use
• Known malignancy or immunocompromised state 3, 4

CT abnormalities are found in 23-41% of first-time seizure presentations; 22% of patients with normal neurologic exams still have abnormal imaging. 3

Deferred outpatient MRI is acceptable for low-risk patients who have returned to baseline, have normal neurologic exam, no high-risk features, and reliable follow-up—MRI is more sensitive for epileptogenic lesions. 3

Disposition Decisions

Safe discharge criteria:

• Returned to clinical baseline
• Normal neurological examination
• No persistent altered mental status
• No abnormal investigation results requiring inpatient management
• Reliable outpatient follow-up 3, 4

Admission indications:

• Persistent abnormal neurological examination
• Failure to return to baseline
• Abnormal investigation results requiring inpatient management
• Postictal focal deficit that does not quickly resolve 3, 4

Antiepileptic Drug Initiation After First Seizure

Do not initiate long-term anticonvulsants in the ED for:

• Single, self-limiting seizure at stroke onset or within 24 hours (considered "immediate" post-stroke seizure). 5
• First unprovoked seizure in otherwise healthy patients—treatment reduces 2-year recurrence risk but does not improve long-term outcomes or mortality. 3, 4
• Provoked seizures (metabolic, toxic, withdrawal). 3

The number needed to treat to prevent one recurrence within 2 years is 14—exposing many patients to medication adverse effects without proven benefit. 3, 4

Consider AED initiation only for:

• Recurrent seizures during hospitalization (treat as per standard seizure protocols). 5
• First seizure in setting of remote symptomatic brain disease (prior stroke, TBI, tumor). 3
• After a second unprovoked seizure. 4

Seizure Recurrence Risk Counseling

• Mean time to first recurrence is 121 minutes (median 90 minutes); 85% of early recurrences occur within 6 hours of ED presentation. 3, 4
• Overall 24-hour recurrence rate is 19%, decreasing to 9% when alcohol-related events and focal CT lesions are excluded. 3
• Nonalcoholic patients with new-onset seizures have lowest recurrence rate (9.4%); alcoholic patients with seizure history have highest (25.2%). 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
• Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried. 1
• Prophylactic anticonvulsants are not recommended in acute stroke or first seizure—evidence suggests possible harm with negative effects on neurological recovery. 5
• Do not use intramuscular diazepam due to erratic absorption—use rectal route instead if IM administration is being considered. 1
• Avoid attributing 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

Monitoring in Refractory Cases

• Continuous EEG monitoring is essential throughout anesthetic infusion, tapering process, and for at least 24-48 hours after discontinuation—breakthrough seizures occur in >50% and are often only detectable by EEG. 1
• Continuous vital sign monitoring, particularly respiratory status and blood pressure. 5, 1
• Be prepared to provide respiratory support regardless of administration route. 5, 1

Prognosis

• Overall mortality for status epilepticus ranges from 5-22%, increasing to 65% in refractory cases. 1
• Mortality and morbidity are highest with SE associated with CNS infections. 6
• Outcome depends on underlying etiology, age, rapidity of treatment, and adequacy of care. 6